Back to resultsSafety, PK and Efficacy Study of SJP-0132 in Subjects With Dry Eye Disease
Primary Purpose
Dry Eye Disease, Dry Eye Syndrome
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SJP-0132
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye Disease
Eligibility Criteria
Inclusion Criteria:
- Body mass index (BMI) within 18.5 to 30.0 kg/m2 (inclusive) and body weight between 45 kg and 100 kg
- Generally healthy as determined by medical history, physical examinations, clinical laboratory examination, and ophthalmologic examinations performed at Screening
- Have a subject reported history of Dry Eye Disease in both eyes for at least 6 months prior to Screening
- Non-smoker or ex-smoker for >12 months
Exclusion Criteria:
- Have clinically significant systemic or ophthalmic disease
- Has a positive serum pregnancy test at Screening or urine pregnancy test
- Have had significant blood loss or have donated or received one or more units (450 mL) of blood or plasma within 30 days before randomization
- Have used or anticipates use of any prescription or over-the-counter medication, including topical medications such as ophthalmic solutions, nasal drops or spray, vitamins, alternative and complementary medicines (including herbal formulations) within 14 days or 5 half-lives (whichever is longer) before randomization or at any time during the study
- Use or anticipates use of prescribed dry eye medications within 28 days prior to randomization or at any time during the study
- Have used or anticipates use CYP3A4 inducers, such as St. John's Wort, within 14 days before randomization or at any time during the study.
- Have consumed red wine, grapefruit or grapefruit juice, Seville oranges, star fruit, or any products containing these items, or any foods that may inhibit CYP3A4, within 48 hours before randomization and throughout the duration of the study
- Have a positive urine alcohol or urine drug test at Screening or Day -1
- Contact lens wearers who cannot discontinue the wear over the trial period
- Have undergone eye surgery (including laser surgery) within the last 12 months or whom the Investigator considers unsuitable
- Have a best corrected visual acuity (BCVA) worse than 20/100 in either eye
- History of permanent punctal occlusion (cautery or laser) or current use of punctal plugs
- Any corneal abnormality or disease which might impact normal tear film spreading
- Active or history of significant corneal disease
- Known allergy or sensitivity to fluorescein, lissamine green or any of the study medications
Other protocol-defined Inclusion/Exclusion Criteria may apply
Sites / Locations
- Senju Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Cohort 1-4: SJP-0132
Cohort 1-4: Placebo
Cohort 5-6: SJP-0132
Cohort 5-6: Placebo
Arm Description
Each cohort will receive a single dose of 1 of 4 strengths of SJP-0132
Single dose of placebo
Cohort 5 SJP-0132 will receive the second maximum acceptable dose from Cohorts 1-4 for 4 weeks. Cohort 6 SJP-0132 will receive the maximum acceptable dose from Cohorts 1-4 for 4 weeks
Multiple dose placebo for 4 weeks
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events by Severity in Each Cohort
Number of participants with adverse events by severity are summarize in each cohort. Adverse events are reported as Treatment-Emergent Adverse Events (TEAEs), which are defined as any event not present before exposure to the study drug or any event already presented that worsened in either intensity or frequency after exposure to the study drug.
Number of Subjects With Abnormal Changes in Laboratory Parameters, Vital Signs, and/or Physical and Ophthalmologic Observations in Each Cohort
Clinical laboratory parameters include hematology, clinical chemistry, urinalysis, and serology. Vital signs include diastolic blood pressure, systolic blood pressure, heart rate, respiratory rate, and body temperature. Ophthalmologic observations include examination of visual acuity, slit lamp biomicroscopy, Schirmer I, intraocular pressure, and ophthalmoscopy.
Maximum Plasma Concentration (Cmax)
The results are from the maximum plasma concentration (Cmax) on Day 1. The blood for pharmacokinetics assessment was collected at 0, 0.25, 0.5, 1, 2, 4, 8, and 12 hours after dosing on Day 1 for Cohorts 1 to 4. The blood for pharmacokinetics assessment was collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1 for Cohorts 5 and 6.
Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC0-last)
Area under the plasma concentration-time curves (AUCs) for Cohorts 1 to 4 were calculated using the plasma collected at 0, 0.25, 0.5, 1, 2, 4, 8, and 12 hours after dosing on Day 1, and those for Cohorts 5 and 6 were calculated using the plasma collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1.
Accumulation Ratio (Rac) After Multiple Dosing
Plasma were collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1, pre-dose on Day 2, Day 4 and Day 8. Accumulation ratios calculated as (predose plasma concentration [Ctrough] on Day 4) / (Ctrough on Day 2) and (Ctrough on Day 8) / (Ctrough on Day 2)
Change From Baseline in Eye Dryness Symptom (VAS) at 4hour on Day 29
Visual analog scale (VAS): "0" mean none, and "100" mean the worst imaginable for the symptom question.
Change From Baseline in Corneal Fluorescein Staining (CFS) Score at the Central Zone on Day 29
Change from baseline of central zone CFS score at the central zone on Day 29. CFS score at the central zone ranged from 0 to 5, where '0' represents no fluorescein staining, and '5' represents severe staining on the cornea. The higher scores mean worse outcomes. Results from the study eye are reported.
Secondary Outcome Measures
Change From Baseline in Eye Dryness Symptom by Visual Analog Scale (VAS) in Each Timepoints
Visual analog scale (VAS): "0" mean none, and "100" mean the worst imaginable for the symptom question. Results from pre-dose are reported.
Change From Baseline in Corneal Fluorescein Staining (CFS) Score at Total Zone in Each Timepoints
Change from baseline of CFS score at the total zone of pre-dose in each time point.
Total zone means a summary of central, superior, inferior, nasal, and temporal zones.
The range of the score in each zone is 0 to 5 points, and the total score is 25 points. The higher scores mean worse outcomes.
Change From Baseline in Conjunctival Lissamine Green Staining (CLGS) Score at Total Zone in Each Timepoints
The score in each zone is 0 to 5 points, and the maximum total score is 30 points. The higher scores mean worse outcomes. Results from the study eye are reported.
Change From Baseline in Lid Wiper Epitheliopathy Score in Each Timepoints
Lissamine green staining of the lid wiper was graded from 0 to 3. The higher scores mean worse outcomes. Results from the study eye are reported.
Change From Baseline in Tear Film Break-up Time (TFBUT) in Each Timepoints
Tear film break-up time is the time taken for the first dry spot to appear on the cornea after a complete blink.
Change From Baseline in Ocular Surface Disease Index (OSDI)
The OSDI questionnaire consists of 12 questions regarding ocular symptoms, environmental triggers, and vision-related functioning. The participant was asked to rate each question using a 5-point scale (0 to 4), where 0 = none of the time; 1 = some of the time; 2 = half of the time; 3 = most of the time; and 4 = all of the time. The total OSDI was calculated from the raw scores of each of the 12 questions based on the formula: ([sum of scores for all questions answered] X 25)/([total number of questions answered]).
The OSDI can range from 0 (normal) to 100 (abnormal).
Change From Baseline in Dry Eye Questionnaire 5 (DEQ-5) Scores
The participants rated the frequency on a scale of 0 (never) to 4 (constant) with which they have experienced 3 symptoms (watery eyes, discomfort and dryness). The participant was also asked to rate the intensity of discomfort and dryness on a scale of 0 (never have it) to 5 (very intense). Total DEQ-5 score was the sum of scores for frequency and intensity of dryness and discomfort plus frequency of watery eyes. Maximum score is 22.
Higher scores mean a worse outcome.
Change in Matrix Metalloproteinase-9 (MMP-9)
Levels of the inflammatory marker Matrix Metalloproteinase-9 (MMP-9) were measured in each eye using InflammaDry. The test was recorded as either positive or negative. Results from the study eye are reported.
Full Information
NCT ID
NCT04139122
First Posted
October 14, 2019
Last Updated
March 29, 2023
Sponsor
Senju Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04139122
Brief Title
Safety, PK and Efficacy Study of SJP-0132 in Subjects With Dry Eye Disease
Official Title
A Randomized, Double-Masked, Single-Center, Placebo-Controlled Single and Multiple Ascending Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Efficacy of SJP-0132 in Subjects With Dry Eye Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
October 5, 2019 (Actual)
Primary Completion Date
March 3, 2020 (Actual)
Study Completion Date
March 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Senju Pharmaceutical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is the first study in humans to evaluate the effectiveness of SJP-0132 in the treatment of dry eye disease. This study will evaluate the safety, tolerability, efficacy, and pharmacokinetics of single- and multiple-dose regimens of SJP-0132 in subjects with dry eye disease
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Disease, Dry Eye Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
89 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1-4: SJP-0132
Arm Type
Experimental
Arm Description
Each cohort will receive a single dose of 1 of 4 strengths of SJP-0132
Arm Title
Cohort 1-4: Placebo
Arm Type
Placebo Comparator
Arm Description
Single dose of placebo
Arm Title
Cohort 5-6: SJP-0132
Arm Type
Experimental
Arm Description
Cohort 5 SJP-0132 will receive the second maximum acceptable dose from Cohorts 1-4 for 4 weeks. Cohort 6 SJP-0132 will receive the maximum acceptable dose from Cohorts 1-4 for 4 weeks
Arm Title
Cohort 5-6: Placebo
Arm Type
Placebo Comparator
Arm Description
Multiple dose placebo for 4 weeks
Intervention Type
Drug
Intervention Name(s)
SJP-0132
Intervention Description
SJP-0132 is administered as an eye drop
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo is administered as an eye drop
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events by Severity in Each Cohort
Description
Number of participants with adverse events by severity are summarize in each cohort. Adverse events are reported as Treatment-Emergent Adverse Events (TEAEs), which are defined as any event not present before exposure to the study drug or any event already presented that worsened in either intensity or frequency after exposure to the study drug.
Time Frame
Day 2 for cohort 1-4, Day 29 for cohort 5-6
Title
Number of Subjects With Abnormal Changes in Laboratory Parameters, Vital Signs, and/or Physical and Ophthalmologic Observations in Each Cohort
Description
Clinical laboratory parameters include hematology, clinical chemistry, urinalysis, and serology. Vital signs include diastolic blood pressure, systolic blood pressure, heart rate, respiratory rate, and body temperature. Ophthalmologic observations include examination of visual acuity, slit lamp biomicroscopy, Schirmer I, intraocular pressure, and ophthalmoscopy.
Time Frame
Day 2 for cohort 1-4, Day 29 for cohort 5-6
Title
Maximum Plasma Concentration (Cmax)
Description
The results are from the maximum plasma concentration (Cmax) on Day 1. The blood for pharmacokinetics assessment was collected at 0, 0.25, 0.5, 1, 2, 4, 8, and 12 hours after dosing on Day 1 for Cohorts 1 to 4. The blood for pharmacokinetics assessment was collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1 for Cohorts 5 and 6.
Time Frame
Day 1
Title
Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC0-last)
Description
Area under the plasma concentration-time curves (AUCs) for Cohorts 1 to 4 were calculated using the plasma collected at 0, 0.25, 0.5, 1, 2, 4, 8, and 12 hours after dosing on Day 1, and those for Cohorts 5 and 6 were calculated using the plasma collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1.
Time Frame
Day 1
Title
Accumulation Ratio (Rac) After Multiple Dosing
Description
Plasma were collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1, pre-dose on Day 2, Day 4 and Day 8. Accumulation ratios calculated as (predose plasma concentration [Ctrough] on Day 4) / (Ctrough on Day 2) and (Ctrough on Day 8) / (Ctrough on Day 2)
Time Frame
Day 2, 4, 8
Title
Change From Baseline in Eye Dryness Symptom (VAS) at 4hour on Day 29
Description
Visual analog scale (VAS): "0" mean none, and "100" mean the worst imaginable for the symptom question.
Time Frame
Day 29
Title
Change From Baseline in Corneal Fluorescein Staining (CFS) Score at the Central Zone on Day 29
Description
Change from baseline of central zone CFS score at the central zone on Day 29. CFS score at the central zone ranged from 0 to 5, where '0' represents no fluorescein staining, and '5' represents severe staining on the cornea. The higher scores mean worse outcomes. Results from the study eye are reported.
Time Frame
Day 29
Secondary Outcome Measure Information:
Title
Change From Baseline in Eye Dryness Symptom by Visual Analog Scale (VAS) in Each Timepoints
Description
Visual analog scale (VAS): "0" mean none, and "100" mean the worst imaginable for the symptom question. Results from pre-dose are reported.
Time Frame
Day 29
Title
Change From Baseline in Corneal Fluorescein Staining (CFS) Score at Total Zone in Each Timepoints
Description
Change from baseline of CFS score at the total zone of pre-dose in each time point.
Total zone means a summary of central, superior, inferior, nasal, and temporal zones.
The range of the score in each zone is 0 to 5 points, and the total score is 25 points. The higher scores mean worse outcomes.
Time Frame
Day 8, 15, 22, 29
Title
Change From Baseline in Conjunctival Lissamine Green Staining (CLGS) Score at Total Zone in Each Timepoints
Description
The score in each zone is 0 to 5 points, and the maximum total score is 30 points. The higher scores mean worse outcomes. Results from the study eye are reported.
Time Frame
Day 8, 15, 22, 29
Title
Change From Baseline in Lid Wiper Epitheliopathy Score in Each Timepoints
Description
Lissamine green staining of the lid wiper was graded from 0 to 3. The higher scores mean worse outcomes. Results from the study eye are reported.
Time Frame
Day 8, 15, 22, 29
Title
Change From Baseline in Tear Film Break-up Time (TFBUT) in Each Timepoints
Description
Tear film break-up time is the time taken for the first dry spot to appear on the cornea after a complete blink.
Time Frame
Day 8, 15, 22, 29
Title
Change From Baseline in Ocular Surface Disease Index (OSDI)
Description
The OSDI questionnaire consists of 12 questions regarding ocular symptoms, environmental triggers, and vision-related functioning. The participant was asked to rate each question using a 5-point scale (0 to 4), where 0 = none of the time; 1 = some of the time; 2 = half of the time; 3 = most of the time; and 4 = all of the time. The total OSDI was calculated from the raw scores of each of the 12 questions based on the formula: ([sum of scores for all questions answered] X 25)/([total number of questions answered]).
The OSDI can range from 0 (normal) to 100 (abnormal).
Time Frame
Day 8, 15, 22, 29
Title
Change From Baseline in Dry Eye Questionnaire 5 (DEQ-5) Scores
Description
The participants rated the frequency on a scale of 0 (never) to 4 (constant) with which they have experienced 3 symptoms (watery eyes, discomfort and dryness). The participant was also asked to rate the intensity of discomfort and dryness on a scale of 0 (never have it) to 5 (very intense). Total DEQ-5 score was the sum of scores for frequency and intensity of dryness and discomfort plus frequency of watery eyes. Maximum score is 22.
Higher scores mean a worse outcome.
Time Frame
Day 29
Title
Change in Matrix Metalloproteinase-9 (MMP-9)
Description
Levels of the inflammatory marker Matrix Metalloproteinase-9 (MMP-9) were measured in each eye using InflammaDry. The test was recorded as either positive or negative. Results from the study eye are reported.
Time Frame
Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Body mass index (BMI) within 18.5 to 30.0 kg/m2 (inclusive) and body weight between 45 kg and 100 kg
Generally healthy as determined by medical history, physical examinations, clinical laboratory examination, and ophthalmologic examinations performed at Screening
Have a subject reported history of Dry Eye Disease in both eyes for at least 6 months prior to Screening
Non-smoker or ex-smoker for >12 months
Exclusion Criteria:
Have clinically significant systemic or ophthalmic disease
Has a positive serum pregnancy test at Screening or urine pregnancy test
Have had significant blood loss or have donated or received one or more units (450 mL) of blood or plasma within 30 days before randomization
Have used or anticipates use of any prescription or over-the-counter medication, including topical medications such as ophthalmic solutions, nasal drops or spray, vitamins, alternative and complementary medicines (including herbal formulations) within 14 days or 5 half-lives (whichever is longer) before randomization or at any time during the study
Use or anticipates use of prescribed dry eye medications within 28 days prior to randomization or at any time during the study
Have used or anticipates use CYP3A4 inducers, such as St. John's Wort, within 14 days before randomization or at any time during the study.
Have consumed red wine, grapefruit or grapefruit juice, Seville oranges, star fruit, or any products containing these items, or any foods that may inhibit CYP3A4, within 48 hours before randomization and throughout the duration of the study
Have a positive urine alcohol or urine drug test at Screening or Day -1
Contact lens wearers who cannot discontinue the wear over the trial period
Have undergone eye surgery (including laser surgery) within the last 12 months or whom the Investigator considers unsuitable
Have a best corrected visual acuity (BCVA) worse than 20/100 in either eye
History of permanent punctal occlusion (cautery or laser) or current use of punctal plugs
Any corneal abnormality or disease which might impact normal tear film spreading
Active or history of significant corneal disease
Known allergy or sensitivity to fluorescein, lissamine green or any of the study medications
Other protocol-defined Inclusion/Exclusion Criteria may apply
Facility Information:
Facility Name
Senju Investigational Site
City
Cypress
State/Province
California
ZIP/Postal Code
90630
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety, PK and Efficacy Study of SJP-0132 in Subjects With Dry Eye Disease
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