search
Back to results

A Study of MDI-1228_mesylate Ophthalmic Solution in Healthy Adults and Participants With Allergic Conjunctivitis

Primary Purpose

Allergic Conjunctivitis

Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
MDI-1228_mesylate Ophthalmic Solution
Placebo
Sponsored by
Shanghai Medinno Pharmaceutical Technology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Allergic Conjunctivitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Weight ≥ 50 kg for males, ≥ 45 kg for females, with the BMI (BMI = weight[kg]/height[m]2) between 18 and 32 (inclusive) The corrected visual acuity (CVA) of both eyes should be 6/6 or 20/20 (Snellen chart), with an intraocular pressure between 10 and 21 mmHg (inclusive) and a difference in intraocular pressure between the 2 eyes < 5 mmHg. Normal vital signs after ≥ 5 minutes resting supine or semi supine position: ≥ 90 mmHg and ≤160 mmHg (systolic blood pressure) ≥50 mmHg and ≤ 95 mmHg (diastolic blood pressure) ≥ 45 beats per minute (bpm) and ≤ 100 bpm (heart rate) Body temperature >35.5℃ and ≤37.7℃ Standard 12-lead ECG parameters after ≥5 minutes resting in supine or semi-supine position with PR > 120 ms and < 220 ms, QRS < 120 ms, QTcF ≤ 450 ms for males and ≤ 470 ms for females, and otherwise normal ECG (all data limits are based on average readings of the ECGs). Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use highly effective contraceptive method as assessed by the PI (OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD) from screening until study completion, including the follow up period for at least 30 days after the last dose of study drug, or be post-menopausal for ≥ 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels at screening for amenorrheic female participants. Females who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible for participation. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study. Males must be surgically sterile (> 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method as assessed by the PI from screening until study completion, including the follow up period, for at least 30 days after the last dose of study drug. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long- acting implantable hormones, injectable hormones, a vaginal ring, or an IUD. Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse as part of their usual lifestyle and are not planning to conceive will also be eligible. Male participants must agree to refrain from donating sperm and female participants from donating ova from screening until study completion, including the follow up period, for at least 90 days after the last dose of study drug. Provides written informed consent and is willing and able to undergo all study procedures and attend the scheduled follow up visit/s per protocol. Are willing to consume clinical research unit (CRU) provided standard meals. Have no neck or back issues which prevents the participant having their head tilted back for dosing at the discretion of the Investigator. For Part A: Single Ascending Dose in Healthy Volunteers Males and females aged 18 to 55 years old (inclusive) Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests, and ECG. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local MM and Sponsor MM as required. Have no abnormal results or abnormal not clinically significant (as determined by the Investigator) results of ocular examinations of both eyes (including slit-lamp examination, corneal fluorescein staining test, light response pupil test, extraocular movement test, visual field test, posterior OCT eye examination, dilated fundus examination) For Part B: Multiple Ascending Doses in Participants with Allergic Conjunctivitis Male and female participants aged 18 to 65 years (inclusive) Positive conjunctival allergen challenge (CAC) for both eyes at screening. During the screening period CAC tests that are positive for the first test will be confirmed by a second test at least 7 days later. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests, vital signs, and ECG, with the exception of abnormal clinically significant results related to allergic conjunctivitis. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local medical monitor (MM) and Sponsor MM as required. Have no abnormal results or have abnormal but not clinically significant (as determined by the investigator) results of ocular examinations of both eyes (including slit-lamp examination, corneal fluorescein staining test, light response pupil test, extraocular movement test, visual field test, posterior optical coherence tomography (OCT) eye examination, dilated fundus examination), except for abnormal signs caused by allergic conjunctivitis (AC) (such as: conjunctival hyperemia, edema, and papillary hypertrophy conjunctiva). Exclusion Criteria: Have a current or past history of clinically significant eye disorder (allergic conjunctivitis condition is not applicable for Part B), circulatory system diseases, respiratory disorders, hepatobiliary disorders, digestive disorders, urinary system diseases, renal disorders, endocrine disorders, immune system disorders, malignancies, metabolic disorders, mental disorders, or nervous system diseases that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the participant by virtue of their participation in the study. Participant with a history of uncomplicated kidney stones (defined as spontaneous passage and no recurrence in the last 5 years); uncomplicated cholecystectomy; Gilbert's syndrome; a past history of being treated by non-current depression may be enrolled in the study at the discretion of the Investigator. Participants with a history of childhood asthma (without hospitalization) that has symptomatically resolved and remains untreated may participant. Have healed eye disorders (such as infection, trauma) in either eye within 1 month prior to the first dose. Have a history of intraocular surgery and laser eye surgery in either eye. Used any ocular products (including various eye drops or eye gel) within 14 days or 5 half-lives (whichever is longer) prior to screening. Wore contact lenses within 7 days prior to baseline or need to wear contact lenses throughout the clinical study. Current evidence or history of COVID-19 or influenza-like illness as defined by fever (> 37.7°C) and 2 or more of the following symptoms within 7 days before dosing: cough, sore throat, runny nose, sneezing, limb/joint pain, headache, vomiting/diarrhea in the absence of a known cause, other than influenza or COVID-19 infection. A history of Hepatitis B, Hepatitis C, or HIV infection and/or a positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. Participants who are intolerant of venipuncture blood collection or have poor venous access and/or have a history of fear of needles and hemophobia. Used Janus kinase (JAK) inhibitors or immunosuppressants or any other prescription drugs, traditional Chinese medicines or Chinese patent medicines within 4 weeks prior to Day -1; or used over-the-counter (OTC) drugs or health products within 2 weeks prior to Day -1, unless with a washout period of more than 5 half-lives for products with a longer half-life. Was vaccinated within 2 weeks prior to screening or plan to be vaccinated during the study. Had major surgery within 6 months prior to screening or plan to undergo surgery during the study. Participants who smoked more than 5 cigarettes/pipes/vaping per day on average or excessive use of any nicotine product (> 5 products on average per day) within 3 months prior to screening and not able to abstain from smoking from screening to end of study (EoS). Any other serious medical condition or abnormality that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the study. A positive pre-study drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing (up to 1 false positive result permitted) and may be followed up at the discretion of the Investigator. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of > 21 units for males or > 14 units for females. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits. The participant is unwilling to abstain from alcohol consumption from 24 hours prior to dosing until discharge from the CRU, and for 24 hours prior to all other outpatient visits to the CRU. Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human or humanized antibodies, fusion proteins, MDI-1228_mesylate Ophthalmic Solution excipients, any material used for assessments (e.g., fluorescein, tropicamide, etc), or a history of drug or other allergy including severe allergic reaction that in the opinion of the Investigator contraindicates their participation. Participation in a clinical trial within 30 days before randomization; use of any experimental therapy within 30 days or 5 half-lives prior to randomization, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to randomization, whichever is greater. Pregnant or breastfeeding WOCBP. Donation within the last 3 months of > 499 mL whole blood or within 2 weeks of any volume of plasma. Participant unable to provide written informed consent or participant under guardianship. Unwilling or unable to follow protocol requirements, including attendance at follow up visit/s. Any history of severe ocular trauma in either eye at any time. Any history of previous intraocular or ocular laser surgery or any refractive surgery procedure within the past 6 months of the screening visit in either eye; Current or chronic history of clinically significant ocular disease within the past 3 months of screening visit in either eye. Current or chronic history of ocular infection (bacterial, viral, or fungal) or corneal irritation within the past 3 months of screening visit in either eye. Abnormal tearing, OR expected regular use of prescription or expected use of OTC tear substitutes within 4 weeks prior to Day -1, and for the duration of the study. Previous or expected use of ocular (topical, periocular, intravitreal), local (inhaled or nasal), or systemic steroid or glucocorticoid medications within 4 weeks prior to Day -1, and for the duration of the study. At the ophthalmic Investigator's discretion, any participants who have a history of any significant ocular conditions in either eye that would contraindicate the use of the study medication, or that might affect the study conduct, or the interpretation of the study results. For Part A: Single Ascending Dose in Healthy Volunteers Clinically significant findings as determined by the Investigator in other ocular examinations (e.g., conjunctival hyperemia grade >1, corneal fluorescein staining score ≥ 2, or other chronic or acute eye disorders). History of or presence of Inflammatory ocular disease (iritis, uveitis, herpetic keratitis, AC). Presence of an ocular pathology such as blepharitis, conjunctivitis, uveitis, or any other ocular infection or inflammation. For Part B: Multiple Ascending Doses in Participants with Allergic Conjunctivitis Clinically significant findings in other ocular examinations, except for abnormal signs caused by AC (such as: conjunctival hyperemia, edema, and papillary hypertrophy conjunctiva). Inflammation or infectious disease of the anterior segment other than AC in either eye. Be willing and able to stop current treatment (topical and systemic) for conjunctival allergy for the study duration.

Sites / Locations

  • CMAX Clinical ResearchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental group

Comparator group

Arm Description

Including single dose groups at 2 dose levels (0.1% and 0.3%) and multiple-dose groups at 2 dose levels (0.1% and 0.3%): In Part A, 8 (80%) healthy participants in cohort 1a will receive a single dose of 0.1% MDI-1228_mesylate Ophthalmic Solution; 8 (80%) healthy participants in cohort 2a will receive a single dose 0.3% MDI-1228_mesylate Ophthalmic Solution. In Part B, 8 (80%) participants with allergic conjunctivitis in cohort 1b will receive 0.1% MDI-1228_mesylate Ophthalmic Solution twice daily on Days 1 to 6 and a single dose in the morning of Day 7; 8 (80%) participants with allergic conjunctivitis in cohort 2b will receive 0.3% MDI-1228_mesylate Ophthalmic Solution twice daily on Days 1 to 6 and a single dose in the morning of Day 7.

In Part A, 2 (20%) healthy participants in cohort 1a will receive a single dose of placebo as comparator of 0.1% MDI-1228_mesylate Ophthalmic Solution; 2 (20%) healthy participants in cohort 2a will receive a single dose of placebo as comparator of 0.3% MDI-1228_mesylate Ophthalmic Solution. In Part B, 2 (20%) participants with allergic conjunctivitis in cohort 1b will receive placebo twice daily on Days 1 to 6 and a single dose in the morning of Day 7 as comparator of 0.1% MDI-1228_mesylate Ophthalmic Solution; 2 (20%) participants with allergic conjunctivitis in cohort 2b will receive placebo twice daily on Days 1 to 6 and a single dose in the morning of Day 7 as comparator of 0.3% MDI-1228_mesylate Ophthalmic Solution.

Outcomes

Primary Outcome Measures

Part A and B - Incidence and severity of all systemic or ocular treatment emergent adverse events (TEAEs)
Systemic or ocular TEAEs will be collected from spontaneous reports and direct observation. The investigator will make an assessment of intensity for each TEAE and assign it to one of the Common Terminology Criteria for Adverse Events (CTCAE) categories: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death).
Part A and B - Assessment of vital sign measurement results - respiratory rate
Respiratory rate (breaths/minute) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
Part A and B - Assessment of vital sign measurement results - heart rate
Heart rate (beats/minute) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
Part A and B - Assessment of vital sign measurement results - blood pressure
Blood pressure (mmHg) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
Part A and B - Assessment of vital sign measurement results - body temperature
Body temperature (℃) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
Part A and B - Assessment of physical examination results - general appearance
Assessment of general appearance (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - head, eyes, ears, nose, and throat (HEENT)
Assessment of HEENT (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - neck (including thyroid and nodes)
Assessment of neck (including thyroid and nodes) (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - cardiovascular system
Assessment of cardiovascular system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - respiratory system
Assessment of respiratory system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - gastrointestinal system
Assessment of gastrointestinal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - renal system
Assessment of renal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - neurological system
Assessment of neurological system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - musculoskeletal system
Assessment of musculoskeletal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of physical examination results - skin
Assessment of skin (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of 12-lead electrocardiogram (ECG) results - heart rate
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in heart rate (beats/min) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate (repeat for 3 times), with 1- to 2-minute intervals between ECG readings.
Part A and B - Assessment of 12-lead ECG results - PR interval
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in PR interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
Part A and B - Assessment of 12-lead ECG results - QRS complex
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in QRS complex as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
Part A and B - Assessment of 12-lead ECG results - QT interval corrected with Fridericia Formula (QTcF)
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in QTcF (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
Part A and B - Assessment of 12-lead ECG results - RR interval
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in RR interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
Part A and B - Ophthalmic assessment - corrected visual acuity (CVA)
CVA (6/6 or 20/20 system) will be assessed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Ophthalmic assessment - best corrected visual acuity (BCVA) (for subjects with CVA below 6/6 or 20/20 only)
BCVA examination is required to confirm whether the subject's best-corrected visual acuity is reduced in subjects with visual acuity below 6/6 or 20/20 during the follow-up after the screening period.
Part A and B - Ophthalmic assessment - intraocular pressure
Intraocular pressure (mmHg) will be assessed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Ophthalmic assessment - light response pupil test
Light response pupil test (positive/negative) will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Ophthalmic assessment - extraocular movement test
Extraocular movement test will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Ophthalmic assessment - visual field test
Visual field test will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Ophthalmic assessment - slit-lamp examination
Slit-lamp examination will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Ophthalmic assessment - corneal fluorescein staining test
Corneal fluorescein staining test will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Ophthalmic assessment - dilated fundus examination
Dilated fundus examination will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Ophthalmic assessment - optical coherence tomography (OCT) eye examination
OCT eye examination will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Part A and B - Assessment of hematology results - hemoglobin
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in hemoglobin (g/dL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - hematocrit
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in hematocrit (%) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - red blood cell count
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in red blood cell count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - white blood cell count
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in white blood cell count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - neutrophil count
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in neutrophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - lymphocyte count
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in lymphocyte count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - monocyte count
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in monocyte count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - basophil count
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in basophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - eosinophil count
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in eosinophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of hematology results - platelet count
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in platelet count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of coagulation results - international normalized ratio (INR)
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in INR from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of coagulation results - activated partial thromboplastin time (aPTT)
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in aPTT (seconds) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of coagulation results - prothrombin time (PT)
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in PT (seconds) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - sodium
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood sodium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - potassium
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood potassium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - chloride
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood chloride (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - calcium
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - bicarbonate
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in blood bicarbonate (mmol/L) and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - albumin
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in blood albumin (g/dL) and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - total protein
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in total protein (g/dL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - creatinine
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood creatinine (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - estimated glomerular filtration rate (GFR)
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in estimated GFR (mL/min) and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - urea
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood urea (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - aspartate aminotransferase (AST)
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in AST (units/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - alanine aminotransferase (ALT)
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ALT (units/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - gamma glutamyl transpeptidase (GGT)
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in GGT (units/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - alkaline phosphatase (ALP)
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ALP (units/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - phosphorous
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood phosphorous (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - total bilirubin (direct and indirect)
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in total bilirubin (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - amylase
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood amylase (units/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - cholesterol
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in cholesterol (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - triglycerides
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in triglycerides (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - uric acid
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in uric acid (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - creatine phosphokinase
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in creatine phosphokinase (units/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - lactate dehydrogenase
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in lactate dehydrogenase (units/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - magnesium
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood magnesium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - fasting glucose
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in fasting glucose (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - anion gap
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in anion gap (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - adjusted calcium
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in adjusted calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - globulin
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in globulin (g/dL) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of blood biochemistry results - ionized calcium
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ionized calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of urinalysis results - pH
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in pH from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of urinalysis results - specific gravity
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in specific gravity from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of urinalysis results - urine glucose
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine glucose (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of urinalysis results - urine protein
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine protein (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of urinalysis results - urine ketones
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine ketones (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of urinalysis results - urine blood
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine blood (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
Part A and B - Assessment of scores of conjunctival hyperemia
Scores of conjunctival hyperemia (0 to 4 scores, a higher score indicates a more severe condition) will be assessed to record the change from the pre-dose (Day -1) scores to the post-dose scores (Day 2 for Part A, Day 8 for Part B) in the study eye.
Part A and B - Assessment of scores of corneal staining
Scores of corneal staining (0 to 4 scores, a higher score indicates a more severe condition) will be assessed to record the change from the pre-dose (Day -1) scores to the post-dose scores (Day 2 for Part A, Day 8 for Part B) in the study eye.

Secondary Outcome Measures

Part A - Maximum concentration (Cmax) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Cmax means the highest concentration a drug reaches in the plasma after administration. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Part A and B - Time to maximum concentration (Tmax) of MDI-1228_mesylate Ophthalmic Solution
Tmax refers to the time a drug takes to reach the highest concentration in the plasma after administration. It will be measured after the subject receives a single dose (Part A) or multiple doses (Part B) of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Part A and B - Half-life (T1/2) of MDI-1228_mesylate Ophthalmic Solution
T1/2 refers to the time a drug takes to be eliminated to half of the highest concentration in the plasma after administration. It will be measured after the subject receives a single dose (Part A) or multiple doses (Part B) of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Part A - Systemic clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Systemic CL refers to the total volume of fluid cleared of drug from the body per unit of time, usually expressed in mL/min. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Part A - Volume of distribution (Vd) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Vd refers to fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Part A - Mean retention time (MRT) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
MRT reflects the average time a drug molecule spends in the body. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Part A - Area under curve until time t (AUC0-t) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
AUC0-t refers to area under the plasma concentration-time curve until time t and reflects the actual body exposure to drug after administration at time t. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Part A - Area under curve until infinity (AUC0-∞) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
AUC0-∞ refers to area under the plasma concentration-time curve until infinity and reflects the total body exposure to drug. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Part B - Trough concentration at steady state (Css_min) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Css_min means the lowest concentration of drug in the blood within a steady-state dosing interval. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Part B - Maximum plasma concentration at steady state (Css_max) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Css_max means the highest concentration of drug in the blood observed after intermittent dosage administration. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Part B - Average plasma concentration at steady state (Css_av) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Css_av means the average drug concentration reached during a steady-state intermittent dosing interval. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Part B - Clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
CL means the volume of fluid cleared of drug from the body per unit of time, usually expressed in mL/min. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Part B - Area under the plasma concentration-time curve at steady state (AUCss) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
AUCss reflects the exposure of drug in the body at steady state. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Part B - Coefficient of fluctuation (DF) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
DF reflects difference between the highest and lowest concentration of drug in the body at steady state. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Part B - Assessment of scores in the study and fellow eye of eye itching
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be evaluated using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of eye itching (0 to 4 scores, a higher score indicates a more severe condition) between the following timepoints will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (3, 5 and 7 minutes [±1 minute]) post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (3, 5 and 7 minutes [±1 minute])
Part B - Assessment of scores in the study and fellow eye of eye redness
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of eye redness (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).
Part B - Assessment of scores in the study and fellow eye of tearing
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of tearing (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).
Part B - Assessment of scores in the study and fellow eye of chemosis
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of chemosis (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).

Full Information

First Posted
July 24, 2023
Last Updated
July 24, 2023
Sponsor
Shanghai Medinno Pharmaceutical Technology Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT05969236
Brief Title
A Study of MDI-1228_mesylate Ophthalmic Solution in Healthy Adults and Participants With Allergic Conjunctivitis
Official Title
A Phase 1, First-in-Human, Single-center, Randomized, Double-masked, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy of Single and Multiple Ascending Doses of MDI-1228_mesylate Ophthalmic Solution by Local Instillation in Adult Healthy Volunteers and Participants With Allergic Conjunctivitis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 2023 (Anticipated)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Medinno Pharmaceutical Technology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The goal of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics (PK) profiles* of MDI-1228_mesylate Ophthalmic Solution in patients with allergic conjunctivitis and healthy adult participants. This trial also aims to study the preliminary efficacy of MDI-1228_mesylate Ophthalmic Solution in patients with allergic conjunctivitis. Participants will receive either of the following treatment: MDI-1228_mesylate Ophthalmic Solution, or Placebo** Researchers will observe any changes in heath (if any) in participants receiving the study treatment to evaluate the safety of study drug. Researchers will also focus on any changes in symptoms of patients with allergic conjunctivitis to evaluate the efficacy of study drug. Note: *PK profiles: how the drug interacts with the body. **placebo: a harmless substance that contains no active agents.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allergic Conjunctivitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
This study consists of two parts: Part A: Single ascending dose in healthy volunteers Part B: Multiple ascending doses in participants with allergic conjunctivitis For each part, 20 healthy participants are planned to be enrolled into 1 of the 2 dose cohorts. Within each cohort, participants will be randomized to receive either MDI-1228_mesylate Ophthalmic Solution or placebo. The randomization code and the randomization list will be generated using SAS version 9.4 or the latest available version at time of randomization. Part A Cohort 1a: 0.1% MDI-1228_mesylate Ophthalmic Solution or placebo Cohort 2a: 0.3% MDI-1228_mesylate Ophthalmic Solution or placebo Part B Cohort 1b: 0.1% MDI-1228_mesylate Ophthalmic Solution or placebo Cohort 2b: 0.3% MDI-1228_mesylate Ophthalmic Solution or placebo
Masking
ParticipantInvestigator
Masking Description
The Investigator, other clinical research unit staff, and study participants will remain masked throughout the conduct of the study, except in circumstances where unmasking is determined by the Investigator or Sponsor or Safety review committee to be important for the safety of a participant, or for the purposes of meeting expedited safety reporting requirements, as applicable. In addition, the clinical site monitor, the clinical research organization (CRO; excluding unmasked statistical and clinical monitoring teams) and the Sponsor will be masked to the assigned treatment. The following personnel will remain unmasked: unmasked CRO staff personnel at the bioanalytical laboratory involved in the determination of plasma concentrations of MDI-1228_mesylate Ophthalmic Solution. If an emergency unmasking is required, the Investigator will have immediate access to individual sealed participant codes.
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental group
Arm Type
Experimental
Arm Description
Including single dose groups at 2 dose levels (0.1% and 0.3%) and multiple-dose groups at 2 dose levels (0.1% and 0.3%): In Part A, 8 (80%) healthy participants in cohort 1a will receive a single dose of 0.1% MDI-1228_mesylate Ophthalmic Solution; 8 (80%) healthy participants in cohort 2a will receive a single dose 0.3% MDI-1228_mesylate Ophthalmic Solution. In Part B, 8 (80%) participants with allergic conjunctivitis in cohort 1b will receive 0.1% MDI-1228_mesylate Ophthalmic Solution twice daily on Days 1 to 6 and a single dose in the morning of Day 7; 8 (80%) participants with allergic conjunctivitis in cohort 2b will receive 0.3% MDI-1228_mesylate Ophthalmic Solution twice daily on Days 1 to 6 and a single dose in the morning of Day 7.
Arm Title
Comparator group
Arm Type
Placebo Comparator
Arm Description
In Part A, 2 (20%) healthy participants in cohort 1a will receive a single dose of placebo as comparator of 0.1% MDI-1228_mesylate Ophthalmic Solution; 2 (20%) healthy participants in cohort 2a will receive a single dose of placebo as comparator of 0.3% MDI-1228_mesylate Ophthalmic Solution. In Part B, 2 (20%) participants with allergic conjunctivitis in cohort 1b will receive placebo twice daily on Days 1 to 6 and a single dose in the morning of Day 7 as comparator of 0.1% MDI-1228_mesylate Ophthalmic Solution; 2 (20%) participants with allergic conjunctivitis in cohort 2b will receive placebo twice daily on Days 1 to 6 and a single dose in the morning of Day 7 as comparator of 0.3% MDI-1228_mesylate Ophthalmic Solution.
Intervention Type
Drug
Intervention Name(s)
MDI-1228_mesylate Ophthalmic Solution
Intervention Description
MDI-1228_mesylate Ophthalmic Solution includes 2 strengths: 0.1% (0.4 mL [0.4 mg] free base) 0.3% (0.4 mL [1.2 mg] free base) For each dose, MDI-1228_mesylate Ophthalmic Solution is administered by clinical research unit staff via conjunctival instillation with 2 drops to the right eye (ie, study eye). In Part B of the study, the participants will receive 12 ±1 hours between doses. The manufacturing site for MDI-1228_mesylate Ophthalmic Solution of the clinical supply materials was Tianjin Kingyork Hebei Univision Pharmaceutical Co., Ltd.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The components employed in the placebo formulation are the same as those used for the active formulation except MDI-1228_mesylate is absent. For each dose, the placebo is administered via conjunctival instillation with 2 drops to the right eye (ie, study eye). The manufacturing site for placebo of the clinical supply materials was Tianjin Kingyork Hebei Univision Pharmaceutical Co., Ltd.
Primary Outcome Measure Information:
Title
Part A and B - Incidence and severity of all systemic or ocular treatment emergent adverse events (TEAEs)
Description
Systemic or ocular TEAEs will be collected from spontaneous reports and direct observation. The investigator will make an assessment of intensity for each TEAE and assign it to one of the Common Terminology Criteria for Adverse Events (CTCAE) categories: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death).
Time Frame
From first dose to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of vital sign measurement results - respiratory rate
Description
Respiratory rate (breaths/minute) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of vital sign measurement results - heart rate
Description
Heart rate (beats/minute) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of vital sign measurement results - blood pressure
Description
Blood pressure (mmHg) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of vital sign measurement results - body temperature
Description
Body temperature (℃) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - general appearance
Description
Assessment of general appearance (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - head, eyes, ears, nose, and throat (HEENT)
Description
Assessment of HEENT (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - neck (including thyroid and nodes)
Description
Assessment of neck (including thyroid and nodes) (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - cardiovascular system
Description
Assessment of cardiovascular system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - respiratory system
Description
Assessment of respiratory system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - gastrointestinal system
Description
Assessment of gastrointestinal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - renal system
Description
Assessment of renal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - neurological system
Description
Assessment of neurological system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - musculoskeletal system
Description
Assessment of musculoskeletal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of physical examination results - skin
Description
Assessment of skin (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of 12-lead electrocardiogram (ECG) results - heart rate
Description
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in heart rate (beats/min) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate (repeat for 3 times), with 1- to 2-minute intervals between ECG readings.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of 12-lead ECG results - PR interval
Description
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in PR interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of 12-lead ECG results - QRS complex
Description
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in QRS complex as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of 12-lead ECG results - QT interval corrected with Fridericia Formula (QTcF)
Description
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in QTcF (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Assessment of 12-lead ECG results - RR interval
Description
12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in RR interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Ophthalmic assessment - corrected visual acuity (CVA)
Description
CVA (6/6 or 20/20 system) will be assessed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Ophthalmic assessment - best corrected visual acuity (BCVA) (for subjects with CVA below 6/6 or 20/20 only)
Description
BCVA examination is required to confirm whether the subject's best-corrected visual acuity is reduced in subjects with visual acuity below 6/6 or 20/20 during the follow-up after the screening period.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Ophthalmic assessment - intraocular pressure
Description
Intraocular pressure (mmHg) will be assessed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Ophthalmic assessment - light response pupil test
Description
Light response pupil test (positive/negative) will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Ophthalmic assessment - extraocular movement test
Description
Extraocular movement test will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Ophthalmic assessment - visual field test
Description
Visual field test will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Ophthalmic assessment - slit-lamp examination
Description
Slit-lamp examination will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Ophthalmic assessment - corneal fluorescein staining test
Description
Corneal fluorescein staining test will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Ophthalmic assessment - dilated fundus examination
Description
Dilated fundus examination will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Ophthalmic assessment - optical coherence tomography (OCT) eye examination
Description
OCT eye examination will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - hemoglobin
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in hemoglobin (g/dL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - hematocrit
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in hematocrit (%) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - red blood cell count
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in red blood cell count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - white blood cell count
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in white blood cell count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - neutrophil count
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in neutrophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - lymphocyte count
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in lymphocyte count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - monocyte count
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in monocyte count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - basophil count
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in basophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - eosinophil count
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in eosinophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of hematology results - platelet count
Description
Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in platelet count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of coagulation results - international normalized ratio (INR)
Description
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in INR from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of coagulation results - activated partial thromboplastin time (aPTT)
Description
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in aPTT (seconds) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of coagulation results - prothrombin time (PT)
Description
A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in PT (seconds) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - sodium
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood sodium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - potassium
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood potassium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - chloride
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood chloride (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - calcium
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - bicarbonate
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in blood bicarbonate (mmol/L) and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - albumin
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in blood albumin (g/dL) and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - total protein
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in total protein (g/dL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - creatinine
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood creatinine (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - estimated glomerular filtration rate (GFR)
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in estimated GFR (mL/min) and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - urea
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood urea (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - aspartate aminotransferase (AST)
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in AST (units/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - alanine aminotransferase (ALT)
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ALT (units/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - gamma glutamyl transpeptidase (GGT)
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in GGT (units/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - alkaline phosphatase (ALP)
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ALP (units/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - phosphorous
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood phosphorous (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - total bilirubin (direct and indirect)
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in total bilirubin (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - amylase
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood amylase (units/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - cholesterol
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in cholesterol (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - triglycerides
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in triglycerides (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - uric acid
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in uric acid (μmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - creatine phosphokinase
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in creatine phosphokinase (units/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - lactate dehydrogenase
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in lactate dehydrogenase (units/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - magnesium
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood magnesium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - fasting glucose
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in fasting glucose (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - anion gap
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in anion gap (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - adjusted calcium
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in adjusted calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - globulin
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in globulin (g/dL) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of blood biochemistry results - ionized calcium
Description
Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ionized calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of urinalysis results - pH
Description
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in pH from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of urinalysis results - specific gravity
Description
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in specific gravity from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of urinalysis results - urine glucose
Description
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine glucose (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of urinalysis results - urine protein
Description
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine protein (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of urinalysis results - urine ketones
Description
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine ketones (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of urinalysis results - urine blood
Description
Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine blood (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.
Time Frame
From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of scores of conjunctival hyperemia
Description
Scores of conjunctival hyperemia (0 to 4 scores, a higher score indicates a more severe condition) will be assessed to record the change from the pre-dose (Day -1) scores to the post-dose scores (Day 2 for Part A, Day 8 for Part B) in the study eye.
Time Frame
From pre-dose to post-dose (Day 2 in Part A, Day 8 in Part B)
Title
Part A and B - Assessment of scores of corneal staining
Description
Scores of corneal staining (0 to 4 scores, a higher score indicates a more severe condition) will be assessed to record the change from the pre-dose (Day -1) scores to the post-dose scores (Day 2 for Part A, Day 8 for Part B) in the study eye.
Time Frame
From pre-dose to post-dose (Day 2 in Part A, Day 8 in Part B)
Secondary Outcome Measure Information:
Title
Part A - Maximum concentration (Cmax) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Description
Cmax means the highest concentration a drug reaches in the plasma after administration. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 7±1 day)
Title
Part A and B - Time to maximum concentration (Tmax) of MDI-1228_mesylate Ophthalmic Solution
Description
Tmax refers to the time a drug takes to reach the highest concentration in the plasma after administration. It will be measured after the subject receives a single dose (Part A) or multiple doses (Part B) of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A and B - Half-life (T1/2) of MDI-1228_mesylate Ophthalmic Solution
Description
T1/2 refers to the time a drug takes to be eliminated to half of the highest concentration in the plasma after administration. It will be measured after the subject receives a single dose (Part A) or multiple doses (Part B) of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 7±1 day in Part A, Day 14±1 day in Part B)
Title
Part A - Systemic clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Description
Systemic CL refers to the total volume of fluid cleared of drug from the body per unit of time, usually expressed in mL/min. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 7±1 day)
Title
Part A - Volume of distribution (Vd) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Description
Vd refers to fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 7±1 day)
Title
Part A - Mean retention time (MRT) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Description
MRT reflects the average time a drug molecule spends in the body. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 7±1 day)
Title
Part A - Area under curve until time t (AUC0-t) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Description
AUC0-t refers to area under the plasma concentration-time curve until time t and reflects the actual body exposure to drug after administration at time t. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 7±1 day)
Title
Part A - Area under curve until infinity (AUC0-∞) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution
Description
AUC0-∞ refers to area under the plasma concentration-time curve until infinity and reflects the total body exposure to drug. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 7±1 day)
Title
Part B - Trough concentration at steady state (Css_min) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Description
Css_min means the lowest concentration of drug in the blood within a steady-state dosing interval. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 14±1 day)
Title
Part B - Maximum plasma concentration at steady state (Css_max) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Description
Css_max means the highest concentration of drug in the blood observed after intermittent dosage administration. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 14±1 day)
Title
Part B - Average plasma concentration at steady state (Css_av) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Description
Css_av means the average drug concentration reached during a steady-state intermittent dosing interval. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 14±1 day)
Title
Part B - Clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Description
CL means the volume of fluid cleared of drug from the body per unit of time, usually expressed in mL/min. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 14±1 day)
Title
Part B - Area under the plasma concentration-time curve at steady state (AUCss) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Description
AUCss reflects the exposure of drug in the body at steady state. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 14±1 day)
Title
Part B - Coefficient of fluctuation (DF) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution
Description
DF reflects difference between the highest and lowest concentration of drug in the body at steady state. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).
Time Frame
Post-first dose on Day 1 to EOS (Day 14±1 day)
Title
Part B - Assessment of scores in the study and fellow eye of eye itching
Description
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be evaluated using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of eye itching (0 to 4 scores, a higher score indicates a more severe condition) between the following timepoints will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (3, 5 and 7 minutes [±1 minute]) post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (3, 5 and 7 minutes [±1 minute])
Time Frame
Post-first dose on Day 1 to end of treatment (Day 7)
Title
Part B - Assessment of scores in the study and fellow eye of eye redness
Description
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of eye redness (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).
Time Frame
Post-first dose on Day 1 to end of treatment (Day 7)
Title
Part B - Assessment of scores in the study and fellow eye of tearing
Description
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of tearing (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).
Time Frame
Post-first dose on Day 1 to end of treatment (Day 7)
Title
Part B - Assessment of scores in the study and fellow eye of chemosis
Description
Preliminarily efficacy after multiple doses of MDI-1228_mesylate Ophthalmic Solution in participants with allergic conjunctivitis will be performed using the conjunctival allergen challenge (CAC) Model. Changes in scores in the study and fellow eye of chemosis (0 to 3 scores, a higher score indicates a more severe condition) between the following time points will be assessed: post-first dose on Day 1 compared to the pre- dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]). post-dose on Day 7 compared to the pre-dose scores at baseline post-CAC (7, 15, and 20 minutes [±1 minute]).
Time Frame
Post-first dose on Day 1 to end of treatment (Day 7)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Weight ≥ 50 kg for males, ≥ 45 kg for females, with the BMI (BMI = weight[kg]/height[m]2) between 18 and 32 (inclusive) The corrected visual acuity (CVA) of both eyes should be 6/6 or 20/20 (Snellen chart), with an intraocular pressure between 10 and 21 mmHg (inclusive) and a difference in intraocular pressure between the 2 eyes < 5 mmHg. Normal vital signs after ≥ 5 minutes resting supine or semi supine position: ≥ 90 mmHg and ≤160 mmHg (systolic blood pressure) ≥50 mmHg and ≤ 95 mmHg (diastolic blood pressure) ≥ 45 beats per minute (bpm) and ≤ 100 bpm (heart rate) Body temperature >35.5℃ and ≤37.7℃ Standard 12-lead ECG parameters after ≥5 minutes resting in supine or semi-supine position with PR > 120 ms and < 220 ms, QRS < 120 ms, QTcF ≤ 450 ms for males and ≤ 470 ms for females, and otherwise normal ECG (all data limits are based on average readings of the ECGs). Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use highly effective contraceptive method as assessed by the PI (OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD) from screening until study completion, including the follow up period for at least 30 days after the last dose of study drug, or be post-menopausal for ≥ 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels at screening for amenorrheic female participants. Females who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible for participation. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study. Males must be surgically sterile (> 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method as assessed by the PI from screening until study completion, including the follow up period, for at least 30 days after the last dose of study drug. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long- acting implantable hormones, injectable hormones, a vaginal ring, or an IUD. Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse as part of their usual lifestyle and are not planning to conceive will also be eligible. Male participants must agree to refrain from donating sperm and female participants from donating ova from screening until study completion, including the follow up period, for at least 90 days after the last dose of study drug. Provides written informed consent and is willing and able to undergo all study procedures and attend the scheduled follow up visit/s per protocol. Are willing to consume clinical research unit (CRU) provided standard meals. Have no neck or back issues which prevents the participant having their head tilted back for dosing at the discretion of the Investigator. For Part A: Single Ascending Dose in Healthy Volunteers Males and females aged 18 to 55 years old (inclusive) Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests, and ECG. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local MM and Sponsor MM as required. Have no abnormal results or abnormal not clinically significant (as determined by the Investigator) results of ocular examinations of both eyes (including slit-lamp examination, corneal fluorescein staining test, light response pupil test, extraocular movement test, visual field test, posterior OCT eye examination, dilated fundus examination) For Part B: Multiple Ascending Doses in Participants with Allergic Conjunctivitis Male and female participants aged 18 to 65 years (inclusive) Positive conjunctival allergen challenge (CAC) for both eyes at screening. During the screening period CAC tests that are positive for the first test will be confirmed by a second test at least 7 days later. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests, vital signs, and ECG, with the exception of abnormal clinically significant results related to allergic conjunctivitis. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local medical monitor (MM) and Sponsor MM as required. Have no abnormal results or have abnormal but not clinically significant (as determined by the investigator) results of ocular examinations of both eyes (including slit-lamp examination, corneal fluorescein staining test, light response pupil test, extraocular movement test, visual field test, posterior optical coherence tomography (OCT) eye examination, dilated fundus examination), except for abnormal signs caused by allergic conjunctivitis (AC) (such as: conjunctival hyperemia, edema, and papillary hypertrophy conjunctiva). Exclusion Criteria: Have a current or past history of clinically significant eye disorder (allergic conjunctivitis condition is not applicable for Part B), circulatory system diseases, respiratory disorders, hepatobiliary disorders, digestive disorders, urinary system diseases, renal disorders, endocrine disorders, immune system disorders, malignancies, metabolic disorders, mental disorders, or nervous system diseases that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the participant by virtue of their participation in the study. Participant with a history of uncomplicated kidney stones (defined as spontaneous passage and no recurrence in the last 5 years); uncomplicated cholecystectomy; Gilbert's syndrome; a past history of being treated by non-current depression may be enrolled in the study at the discretion of the Investigator. Participants with a history of childhood asthma (without hospitalization) that has symptomatically resolved and remains untreated may participant. Have healed eye disorders (such as infection, trauma) in either eye within 1 month prior to the first dose. Have a history of intraocular surgery and laser eye surgery in either eye. Used any ocular products (including various eye drops or eye gel) within 14 days or 5 half-lives (whichever is longer) prior to screening. Wore contact lenses within 7 days prior to baseline or need to wear contact lenses throughout the clinical study. Current evidence or history of COVID-19 or influenza-like illness as defined by fever (> 37.7°C) and 2 or more of the following symptoms within 7 days before dosing: cough, sore throat, runny nose, sneezing, limb/joint pain, headache, vomiting/diarrhea in the absence of a known cause, other than influenza or COVID-19 infection. A history of Hepatitis B, Hepatitis C, or HIV infection and/or a positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. Participants who are intolerant of venipuncture blood collection or have poor venous access and/or have a history of fear of needles and hemophobia. Used Janus kinase (JAK) inhibitors or immunosuppressants or any other prescription drugs, traditional Chinese medicines or Chinese patent medicines within 4 weeks prior to Day -1; or used over-the-counter (OTC) drugs or health products within 2 weeks prior to Day -1, unless with a washout period of more than 5 half-lives for products with a longer half-life. Was vaccinated within 2 weeks prior to screening or plan to be vaccinated during the study. Had major surgery within 6 months prior to screening or plan to undergo surgery during the study. Participants who smoked more than 5 cigarettes/pipes/vaping per day on average or excessive use of any nicotine product (> 5 products on average per day) within 3 months prior to screening and not able to abstain from smoking from screening to end of study (EoS). Any other serious medical condition or abnormality that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the study. A positive pre-study drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing (up to 1 false positive result permitted) and may be followed up at the discretion of the Investigator. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of > 21 units for males or > 14 units for females. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits. The participant is unwilling to abstain from alcohol consumption from 24 hours prior to dosing until discharge from the CRU, and for 24 hours prior to all other outpatient visits to the CRU. Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human or humanized antibodies, fusion proteins, MDI-1228_mesylate Ophthalmic Solution excipients, any material used for assessments (e.g., fluorescein, tropicamide, etc), or a history of drug or other allergy including severe allergic reaction that in the opinion of the Investigator contraindicates their participation. Participation in a clinical trial within 30 days before randomization; use of any experimental therapy within 30 days or 5 half-lives prior to randomization, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to randomization, whichever is greater. Pregnant or breastfeeding WOCBP. Donation within the last 3 months of > 499 mL whole blood or within 2 weeks of any volume of plasma. Participant unable to provide written informed consent or participant under guardianship. Unwilling or unable to follow protocol requirements, including attendance at follow up visit/s. Any history of severe ocular trauma in either eye at any time. Any history of previous intraocular or ocular laser surgery or any refractive surgery procedure within the past 6 months of the screening visit in either eye; Current or chronic history of clinically significant ocular disease within the past 3 months of screening visit in either eye. Current or chronic history of ocular infection (bacterial, viral, or fungal) or corneal irritation within the past 3 months of screening visit in either eye. Abnormal tearing, OR expected regular use of prescription or expected use of OTC tear substitutes within 4 weeks prior to Day -1, and for the duration of the study. Previous or expected use of ocular (topical, periocular, intravitreal), local (inhaled or nasal), or systemic steroid or glucocorticoid medications within 4 weeks prior to Day -1, and for the duration of the study. At the ophthalmic Investigator's discretion, any participants who have a history of any significant ocular conditions in either eye that would contraindicate the use of the study medication, or that might affect the study conduct, or the interpretation of the study results. For Part A: Single Ascending Dose in Healthy Volunteers Clinically significant findings as determined by the Investigator in other ocular examinations (e.g., conjunctival hyperemia grade >1, corneal fluorescein staining score ≥ 2, or other chronic or acute eye disorders). History of or presence of Inflammatory ocular disease (iritis, uveitis, herpetic keratitis, AC). Presence of an ocular pathology such as blepharitis, conjunctivitis, uveitis, or any other ocular infection or inflammation. For Part B: Multiple Ascending Doses in Participants with Allergic Conjunctivitis Clinically significant findings in other ocular examinations, except for abnormal signs caused by AC (such as: conjunctival hyperemia, edema, and papillary hypertrophy conjunctiva). Inflammation or infectious disease of the anterior segment other than AC in either eye. Be willing and able to stop current treatment (topical and systemic) for conjunctival allergy for the study duration.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Liang Lu, PhD
Phone
+86 19921188051
Email
luliang@med-inno.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sepehr Shakib, PhD
Organizational Affiliation
CMAX Clinical Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Liang Lu, PhD
Organizational Affiliation
Shanghai Medinno Pharmaceutical Technology Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
CMAX Clinical Research
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sepehr Shakib, PhD
Phone
+61 0870887900
Email
Sepehr.shakib@sa.gov.au
First Name & Middle Initial & Last Name & Degree
Sepehr Shakib, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of MDI-1228_mesylate Ophthalmic Solution in Healthy Adults and Participants With Allergic Conjunctivitis

We'll reach out to this number within 24 hrs