Back to resultsA First in Human Study of the Safety, Tolerability and Pharmacokinetics of PRV-002 in Healthy Volunteers
Primary Purpose
Traumatic Brain Injury (TBI)
Status
Unknown status
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
PRV-002
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Traumatic Brain Injury (TBI) focused on measuring Safety, Tolerability, Pharmacokinetics, PRV-002
Eligibility Criteria
Inclusion Criteria:
- Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
- Adult males and females, 18 to 55 years of age (inclusive) at screening.
- Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50 kg at screening.
- Be non-smokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration.
- Have a negative test for cotinine at the screening visit and at check-in on Day -1.
Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit in the Schedules of
Assessments (SoA), including:
- Physical examination without any clinically significant findings
- Systolic BP in the range of 90 to 160 mmHg (inclusive) and diastolic BP in the range of 50 to 95 mmHg (inclusive) after 5 minutes in supine position
- Heart rate in the range of 40 to 100 bpm (inclusive) after 5 minutes rest in supine position
- Body temperature (tympanic or oral) in the range 35.5°C to 37.7°C (inclusive)
- No clinically significant findings in serum chemistry, haematology, coagulation, and urinalysis tests
- Triplicate 12-lead ECG (taken after the volunteer has been supine for at least 5 minutes) with a QTcF ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities
- Pulmonary assessments must be within the normal range (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC] and FEV1/FVC ratio ≥ 80% of normal values; f forced expiratory flow over the middle one half of the FVC [FEF25-75%] > 75% of predicted)
- Oxygen saturation (SpO2) monitor ≥ 95%.
Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the timepoints indicated in the Schedules of Assessments (SoA), including:
- Physical examination without any clinically significant findings
- Systolic BP in the range of 90 to 160 mmHg (inclusive) and diastolic BP in the range of 50 to 95 mmHg (inclusive) after 5 minutes in supine position
- Heart rate in the range of 40 to 100 bpm (inclusive) after 5 minutes rest in supine position
- Body temperature (tympanic or oral) in the range 35.5°C to 37.7°C (inclusive)
- No clinically significant findings in serum chemistry, haematology, coagulation, and urinalysis tests
- Triplicate 12-lead ECG (taken after the volunteer has been supine for at least 5 minutes) with a QTcF ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities
- Pulmonary assessments must be within the normal range (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC] and FEV1/FVC ratio ≥ 80% of normal values; f forced expiratory flow over the middle one half of the FVC [FEF25-75%] > 75% of predicted)
- Oxygen saturation (SpO2) monitor ≥ 95%.
Female volunteers must:
- Be of nonchildbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause
- Have a follicle-stimulating hormone level >40 IU/L at the screening visit),or
- If of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception from signing the consent form until at least 30 days after the last dose of the study drug.
- Male volunteers must agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
- Have suitable venous access for blood sampling.
Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
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Exclusion Criteria:
- History or presence of significant cardiovascular disease
- History or presence of significant pulmonary disease
- History or presence of significant hepatic disease
- History or presence of significant renal disease
- History or presence of significant haematological disease
- History or presence of significant gastrointestinal disease
- History or presence of significant disease
- History or presence of significant endocrine disease
- History or presence of significant immunologic disease
- History or presence of significant dermatologic disease
- History or presence of significant or neurological disease
- No major surgery within the past 3 months determined by the PI to be clinically significant.
- Absence of any acute illness.
- Current infection that requires systemically absorbed antibiotic.
- Current infection that requires systemically absorbed antifungal.
- Current infection that requires systemically absorbed antiparasitic.
- Current infection that requires systemically absorbed antiviral medication.
- Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
- Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
- Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration.
- History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death).
- Known arrythmia
- Liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase, bilirubin (total, conjugated and unconjugated), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
- Liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase
- Liver function test results elevated more than 1.5-fold above the ULN for bilirubin (total)
- Liver function test results elevated more than 1.5-fold above the ULN for bilirubin (conjugated)
- Liver function test results elevated more than 1.5-fold above the ULN for ALP. Volunteers with ALP above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
- Liver function test results elevated more than 1.5-fold above the ULN for AST. Volunteers with AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
- Liver function test results elevated more than 1.5-fold above the ULN for ALT. Volunteers with ALT above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
- Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2) antibodies at the screening visit.
- Positive test results for active hepatitis B surface antigen (HBsAg) antibodies at the screening visit.
- Positive test results for active hepatitis C virus (HCV) antibodies at the screening visit.
- Presence or having sequelae of known to interfere with the absorption, distribution, metabolism, or excretion of drugs such as gastrointestinal, liver, kidney, or other conditions .
- Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN.
- History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) within 12 weeks prior to the screening visit.
- Positive drugs of abuse at the screening visit.
- Positive drugs of abuse at check-in (Day -1).
- Positive alcohol breath test results at the screening visit.
- Positive alcohol breath test results at check-in (Day -1).
- Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 10 days prior to the first study drug administration, - exceptions include use of contraceptives, occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days), ibuprofen (doses of 400 mg up to every 6 hours or 1.6 g per day maximum for no more than 3 consecutive days), topical ointments, and vitamins or dietary supplements.
- Consumption of grapefruit or Seville orange (or products containing grapefruit or Seville orange) within 10 days prior to the first administration of study drug.
- Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer's ability to participate in the trial.
- Known hypersensitivity to any of the study drug ingredients.
- Use of any vaccinations within 14 days prior to the first study drug administration.
- For women of childbearing potential, a positive serum pregnancy test at the screening visit.
- For women of childbearing potential, a positive urine pregnancy test (with confirmatory serum pregnancy test) at check-in (Day -1).
- Females who are breastfeeding or planning to breast feed at any time during the study.
- Donation of blood or plasma within 30 days prior to first study drug administration.
- Loss of whole blood of more than 500 mL within 30 days prior to first study drug administration.
- Receipt of a blood transfusion within 1 year of first study drug administration.
- Participation in another clinical trial of an investigational drug within 60 days of the first study drug administration.
Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
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Sites / Locations
- Nucleus Network Pty Ltd,Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
PRV-002
Placebo comparator
Arm Description
A single dose of PRV-002 will be administered to each study participant in this arm on study Day 1 at the following dose levels: Cohort 1: 9.66 mg Cohort 2: 19.38 mg Cohort 3: 38.7 mg.
A single dose of placebo comparator will be administered to each study participant in this arm on study Day 1. Placebo used is hydroxypropyl beta cyclodextrin (HPβCD)
Outcomes
Primary Outcome Measures
Safety endpoint - Evaluation of the Incidence, severity, and relationship of AEs/SAEs (or ADEs/SADEs) (including withdrawals due to AEs (or ADEs)).
AEs/SAEs (or ADEs/SADEs) to be recorded as written descriptions on case report forms
Safety endpoint - Change from baseline in physical examination findings (Full)
Full physical exam including general appearance, head, ears, eyes, nose and throat, neck (including thyroid and lymph nodes), respiratory system, cardiovascular system, gastrointestinal system, renal system, neurological condition, musculoskeletal system, skin and any other focused assessments suggested by the presence of specific symptoms and measured by written descriptions.
Safety endpoint - Change from baseline in physical examination findings (symptom directed)
Symptom-directed physical examination (focused assessments suggested by the presence of specific symptoms) will be performed if clinically indicated, as determined by the Investigator. The pre-dose physical examination assessment should be performed on the scheduled day, at any time prior to dosing. All other physical examinations will be performed within ± 1 hour of the nominated timepoint. Measured by written descriptions.
Safety endpoint - Change from baseline in vital signs (including changes from baseline in SpO2).
SpO2 measured as percent of oxygen (%)
Safety endpoint - Change from baseline in vital signs (including changes from baseline in blood pressure).
Blood pressure measured for systolic and diastolic pressure as mm of mercury.
Safety endpoint - Change from baseline in vital signs (including changes from baseline in heart rate).
Heart rate measured as beats per minute (BPM)
Safety endpoint - Change from baseline in vital signs (including changes from baseline in respiration rate).
Respiration rate measured as breaths per minute
Safety endpoint - Change from baseline in vital signs (including changes from baseline in body temperature).
Body temperature measured as degrees Celsius (C)
Safety endpoint - Changes from baseline in lung spirometry.
Lung spirometry measured as the ratio of forced expiratory value (FEV1)/ forced vital capacity (FVC) and reported as percentage (%)
Safety endpoint - Change from baseline in ECG parameters of heart rate
Heart ratel measured beats per minute (BPM)
Safety endpoint - Change from baseline in ECG parameters of PR interval, QRS interval, and QT interval
PR interval, QRS interval, and QT interval as measured in milliseconds (ms)
Safety endpoint - Change from baseline in hematocrit values
Hematocrit measured as the percentage of red blood cells in whole blood (%)
Safety endpoint - Change from baseline in hemoglobin values
Hemoglobin measured as the amount of hemoglobin in whole blood measured as grams per deciliter (g/dL)
Safety endpoint - Change from baseline in Red Blood Cell (RBC) indices
RBC measured as the number of million RBCs per microliter (mcL) of blood
Safety endpoint - Change from baseline in Thrombocyte Count (Platelets); White Blood Cells (WBC); Basophils; Eosinophils; Lymphocytes; Monocytes; and Neutrophils.
Platelets measured as the number of cells per microliter (mcL) of blood
Safety endpoint - Change from baseline in the blood hormone level of Dehydroepiandrosterone-sulfate (DHEAS)
Dehydroepiandrosterone sulfate (DHEAS) measured as the number of micrograms per deciliter (µg/dL) of blood
Safety endpoint - Change from baseline in the blood hormone level of dihydrotestosterone (DHT)
Dihydrotestosterone (DHT) measured as the number of nano moles per liter (nmol/L) of blood
Safety endpoint - Change from baseline in the blood hormone level of luteinizing hormone (LH)
Luteinizing hormone (LH) measured as the number of International units per liter (IU/L)
Safety endpoint - Change from baseline in the blood hormone level of dehydroepiandrosterone sulfate (DHEAS)
Dehydroepiandrosterone sulfate (DHEAS) measured as the number of micrograms per deciliter (mcg/dL)
Safety endpoint - Change from baseline in the blood hormone level of thyroid stimulating hormone (TSH)
Thyroid stimulating hormone (TSH) measured as the number of milli-international units per liter (mIU/L)
Safety endpoint - For postmenopausal women only, change from baseline in the blood hormone level of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hGH)
Follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hGH) measured as the number of milli-international units per milliliter (mIU/mL)
Safety endpoint - Change from baseline in the blood hormone level of free thyroxine (FT4), testosterone, and dihydrotestosterone (DHT)
Free thyroxine (FT4), testosterone, and dihydrotestosterone (DHT) measured as the number of nanograms per deciliter (ng/dL)
Safety endpoint - Change from baseline in the blood hormone level of progesterone
Progesterone measured as the number of nanograms per miiliiliter (ng/mL)
Safety endpoint - Change from baseline in the blood hormone level of estradiol (E2) and free trilodothyronine (FT3)
Estradiol (E2) and free trilodothyronine (FT3) measured as the number of picograms per milliliter (pg/mL)
Safety endpoint Change in baseline in clotting factors Partial thromboplastin time (aPTT) and Prothrombin time (PT)
Partial thromboplastin time (aPTT) and Prothrombin time (PT) measured as time to clot in seconds (sec)
Safety endpoint - Change from baseline in the clotting factor Fibrinogen
Fibrinogen measured as the number of milligrams per deciliter (mg/dL)
Safety endpoint - Change from baseline in the clotting factor International Normalized Ratio (INR)
International Normalized Ratio (INR) measured as the ratio of patient PT/control PT
Safety endpoint - Change from baseline in urinalysis parameters bilirubin, blood, glucose, nitrites, protein, and urobilinogen
Bilirubin, blood, glucose, nitrites, protein, and urobilinogen measured as the number of milligrams per deciliter (mg/dL)
Safety endpoint - Change from baseline in urinalysis parameter ketones
Ketones measured as the number of millimoles per liter (mmol/L)
Safety endpoint - Change from baseline in urinalysis parameter leukocyte esterase
Leukocyte esterase measured as negative or positive; number of WBCs per high power field
Safety endpoint - Change from baseline in urinalysis parameter pH
pH measured as pH units
Safety endpoint - Change from baseline in urinalysis parameter specific gravity
Specific gravity measured as specific gravity units as a ratio of density of urine/density of water
Safety endpoint - Change from baseline in serum chemistry parameters globulin, protein, and albumin
Globulin, protein, and albumin measured as grams per deciliter (g/dL)
Safety endpoint - Change from baseline in serum chemistry parameter alkaline phosphatase
Alkaline phosphatase measured as International units per liter (IU/L)
Safety endpoint - Change from baseline in serum chemistry parameters bicarbonate, chloride, sodium, and magnesium
Bicarbonate, chloride, sodium, and magnesium measured as milliequivalents per liter (mEq/L)
Safety endpoint - Change from baseline in serum calcium, glucose, phosphate, creatinine, urea, uric acid, bilirubin (conjugated and unconjugated), high density lipoproteins, low density lipoproteins, total bilirubin, total cholesterol
Calcium, glucose, phosphate, creatinine, urea, uric acid, bilirubin (conjugated and unconjugated), high density lipoproteins, low density lipoproteins, total bilirubin, total cholesterol, triglycerides measured as milligrams per deciliter (mg/dL)
Safety endpoint - Change from baseline in serum chemistry parameters potassium
Potassium measured as millimoles per liter (mmol/L)
Safety endpoint - Change from baseline in serum chemistry parameters lipase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, alanine aminotransferase, and amylase
Lipase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, alanine aminotransferase, and amylase measured as Units per liter (U/L)
Safety endpoint - Change from baseline in virology parameters HIV-1/-2; HBsAg; HCV; SARS-COV-2
HIV-1/-2; HBsAg; HCV; SARS-COV-2 test results measured as negative or positive
Safety endpoint - Change from baseline in drug screen findings for alcohol
Alcohol test results measured as percentage (%)
Safety endpoint - Change from baseline in urine drug screen findings for amphetamines, barbiturates, benzodiazepines, cocaine, cotinine, methamphetamines, opiates, phencyclidine, THC, and tricyclic antidepressants
Urine amphetamines, barbiturates, benzodiazepines, cocaine, cotinine, methamphetamines, opiates, phencyclidine, THC, and tricyclic antidepressants test results measured as nanograms per milliliter (ng/mL)
Safety endpoint - Change from baseline for pregnancy test for serum hCG and urine hCG
Serum hCG and Urine hCG levels measured in milli-international units per liter (mIU/L)
Safety endpoint - Change from baseline for confirmation of postmenopausal status test for FSH
FSH levels measured in milli-international units per liter (mIU/L)
Secondary Outcome Measures
Plasma pharmacokinetics - Cmax
Plasma PRV-002 Cmax measured as microgram per mL (mcg/mL)
Plasma pharmacokinetics - Tmax
Plasma PRV-002 time to Cmax
Plasma pharmacokinetics - area under the curve
Plasma PRV-002 Area under the concentration-time curve from 0 to time of last quantifiable concentration (AUC0-t) measured as min*kBq/mL
Plasma pharmacokinetics - area under the concentration-time curve
Plasma PRV-002 area under the concentration-time curve from 0 to infinity (AUC0-inf) measured as mg*h/L
Plasma pharmacokinetics - apparent terminal elimination half-life t1/2)
Plasma PRV-002 apparent terminal elimination half-life (t1/2) measured in minutes or hours
Plasma pharmacokinetics - terminal elimination rate constant (λz)
Plasma PRV-002 terminal elimination rate constant (λz) measured as elimination rate measured as constant K or Ke ((λz))
Plasma pharmacokinetics total apparent body clearance
Plasma PRV-002 total apparent body clearance measured as (CL/F)
Plasma pharmacokinetics - apparent volume of distribution
Plasma PRV-002 apparent volume of distribution measured as (Vz/F)
Urine pharmacokinetics - cumulative amount of unchanged drug excreted in urine
Urine PRV-002 cumulative amount of unchanged drug excreted (Ae) in urine measured in micrograms per milliliter (mcg/mL)
Urine pharmacokinetics - renal clearance
Urine PRV-002 renal clearance measured as (CLr)
Full Information
NCT ID
NCT05033444
First Posted
August 12, 2021
Last Updated
September 20, 2021
Sponsor
Odyssey Group International, Inc.
Collaborators
Avance Clinical Pty Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05033444
Brief Title
A First in Human Study of the Safety, Tolerability and Pharmacokinetics of PRV-002 in Healthy Volunteers
Official Title
A Phase 1, Randomised, Double-Blind, Placebo-Controlled, First in Human Study of the Safety, Tolerability and Pharmacokinetics of a Single Dose of PRV-002 in Healthy Volunteers.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
September 17, 2021 (Anticipated)
Primary Completion Date
November 30, 2021 (Anticipated)
Study Completion Date
November 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Odyssey Group International, Inc.
Collaborators
Avance Clinical Pty Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of different dose levels of PRV-002 in Health Volunteers
Detailed Description
This Phase 1 study is designed to assess the safety, tolerabilty and pharmcokinetics of different dose levels of PRV-002 in Healthy Volunteers. The study will evaluate 3 dose levels of the investigational product, PRV-002, in 3 cohorts of 8 healthy volunteers per cohort. In each cohort, 6 volunteers will receive the investigational product and 2 volunteers will receive placebo. Dose levels will be evaluated in a sequential manner starting at the lowest dose level.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury (TBI)
Keywords
Safety, Tolerability, Pharmacokinetics, PRV-002
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Randomized, double-blind, placebo-controlled, single ascending dose, multi-cohort study.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants will be randomized in a 3:1 ratio of PRV-002 and Placebo.
The following controls will be employed to maintain the double-blind status of the study:
Nasal Spray containing active drug and placebo will be indistinguishable in appearance
Randomization list will be provided to the study center pharmacist for dispensing purposes and kept in the pharmacy, accessible to the pharmacist and authorized personnel only
PK results for the SRC between cohorts will be presented in a blinded fashion.
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
PRV-002
Arm Type
Experimental
Arm Description
A single dose of PRV-002 will be administered to each study participant in this arm on study Day 1 at the following dose levels:
Cohort 1: 9.66 mg
Cohort 2: 19.38 mg
Cohort 3: 38.7 mg.
Arm Title
Placebo comparator
Arm Type
Placebo Comparator
Arm Description
A single dose of placebo comparator will be administered to each study participant in this arm on study Day 1. Placebo used is hydroxypropyl beta cyclodextrin (HPβCD)
Intervention Type
Drug
Intervention Name(s)
PRV-002
Other Intervention Name(s)
Experimental drug
Intervention Description
Eligible participants will be randomised to receive a single ascending dose of PRV-002 on study Day 1. Dose escalation will be conducted in a total of 3 cohorts. Within each cohort, 6 participants will be randomised to receive a single dose of PRV-002. The starting dose, dose increments and dose range to be evaluated are based on available nonclinical data. PRV-002 dose levels in the range of 0.161 to 0.645 mg/kg will be investigated.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo control
Intervention Description
Placebo used is hydroxypropyl beta cyclodextrin (HPβCD)
Primary Outcome Measure Information:
Title
Safety endpoint - Evaluation of the Incidence, severity, and relationship of AEs/SAEs (or ADEs/SADEs) (including withdrawals due to AEs (or ADEs)).
Description
AEs/SAEs (or ADEs/SADEs) to be recorded as written descriptions on case report forms
Time Frame
Baseline pre-intervention (Day -28 to Day -2 and Day -1); during intervention and immediately afterwards (Day 1); Day 2; and through Day 5.
Title
Safety endpoint - Change from baseline in physical examination findings (Full)
Description
Full physical exam including general appearance, head, ears, eyes, nose and throat, neck (including thyroid and lymph nodes), respiratory system, cardiovascular system, gastrointestinal system, renal system, neurological condition, musculoskeletal system, skin and any other focused assessments suggested by the presence of specific symptoms and measured by written descriptions.
Time Frame
Baseline pre-intervention Day -28 to -2.
Title
Safety endpoint - Change from baseline in physical examination findings (symptom directed)
Description
Symptom-directed physical examination (focused assessments suggested by the presence of specific symptoms) will be performed if clinically indicated, as determined by the Investigator. The pre-dose physical examination assessment should be performed on the scheduled day, at any time prior to dosing. All other physical examinations will be performed within ± 1 hour of the nominated timepoint. Measured by written descriptions.
Time Frame
Baseline pre-intervention Day -1 and and Day 1; Day 2
Title
Safety endpoint - Change from baseline in vital signs (including changes from baseline in SpO2).
Description
SpO2 measured as percent of oxygen (%)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in vital signs (including changes from baseline in blood pressure).
Description
Blood pressure measured for systolic and diastolic pressure as mm of mercury.
Time Frame
Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in vital signs (including changes from baseline in heart rate).
Description
Heart rate measured as beats per minute (BPM)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in vital signs (including changes from baseline in respiration rate).
Description
Respiration rate measured as breaths per minute
Time Frame
Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in vital signs (including changes from baseline in body temperature).
Description
Body temperature measured as degrees Celsius (C)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Changes from baseline in lung spirometry.
Description
Lung spirometry measured as the ratio of forced expiratory value (FEV1)/ forced vital capacity (FVC) and reported as percentage (%)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.25hr, 1hr, 10hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in ECG parameters of heart rate
Description
Heart ratel measured beats per minute (BPM)
Time Frame
Baseline pre-intervention; during intervention and immediately afterwards (Day 1); Day 2; and through Day 5.
Title
Safety endpoint - Change from baseline in ECG parameters of PR interval, QRS interval, and QT interval
Description
PR interval, QRS interval, and QT interval as measured in milliseconds (ms)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 pre-intervention; Day 1 at 0.5hr, 2hr, 6hr; 12hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in hematocrit values
Description
Hematocrit measured as the percentage of red blood cells in whole blood (%)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in hemoglobin values
Description
Hemoglobin measured as the amount of hemoglobin in whole blood measured as grams per deciliter (g/dL)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in Red Blood Cell (RBC) indices
Description
RBC measured as the number of million RBCs per microliter (mcL) of blood
Time Frame
Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in Thrombocyte Count (Platelets); White Blood Cells (WBC); Basophils; Eosinophils; Lymphocytes; Monocytes; and Neutrophils.
Description
Platelets measured as the number of cells per microliter (mcL) of blood
Time Frame
Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in the blood hormone level of Dehydroepiandrosterone-sulfate (DHEAS)
Description
Dehydroepiandrosterone sulfate (DHEAS) measured as the number of micrograms per deciliter (µg/dL) of blood
Time Frame
Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Title
Safety endpoint - Change from baseline in the blood hormone level of dihydrotestosterone (DHT)
Description
Dihydrotestosterone (DHT) measured as the number of nano moles per liter (nmol/L) of blood
Time Frame
Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Title
Safety endpoint - Change from baseline in the blood hormone level of luteinizing hormone (LH)
Description
Luteinizing hormone (LH) measured as the number of International units per liter (IU/L)
Time Frame
Baseline pre-intervention Days -28 to -2
Title
Safety endpoint - Change from baseline in the blood hormone level of dehydroepiandrosterone sulfate (DHEAS)
Description
Dehydroepiandrosterone sulfate (DHEAS) measured as the number of micrograms per deciliter (mcg/dL)
Time Frame
Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Title
Safety endpoint - Change from baseline in the blood hormone level of thyroid stimulating hormone (TSH)
Description
Thyroid stimulating hormone (TSH) measured as the number of milli-international units per liter (mIU/L)
Time Frame
Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Title
Safety endpoint - For postmenopausal women only, change from baseline in the blood hormone level of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hGH)
Description
Follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hGH) measured as the number of milli-international units per milliliter (mIU/mL)
Time Frame
Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Title
Safety endpoint - Change from baseline in the blood hormone level of free thyroxine (FT4), testosterone, and dihydrotestosterone (DHT)
Description
Free thyroxine (FT4), testosterone, and dihydrotestosterone (DHT) measured as the number of nanograms per deciliter (ng/dL)
Time Frame
Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Title
Safety endpoint - Change from baseline in the blood hormone level of progesterone
Description
Progesterone measured as the number of nanograms per miiliiliter (ng/mL)
Time Frame
Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Title
Safety endpoint - Change from baseline in the blood hormone level of estradiol (E2) and free trilodothyronine (FT3)
Description
Estradiol (E2) and free trilodothyronine (FT3) measured as the number of picograms per milliliter (pg/mL)
Time Frame
Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Title
Safety endpoint Change in baseline in clotting factors Partial thromboplastin time (aPTT) and Prothrombin time (PT)
Description
Partial thromboplastin time (aPTT) and Prothrombin time (PT) measured as time to clot in seconds (sec)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in the clotting factor Fibrinogen
Description
Fibrinogen measured as the number of milligrams per deciliter (mg/dL)
Time Frame
Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in the clotting factor International Normalized Ratio (INR)
Description
International Normalized Ratio (INR) measured as the ratio of patient PT/control PT
Time Frame
Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5
Title
Safety endpoint - Change from baseline in urinalysis parameters bilirubin, blood, glucose, nitrites, protein, and urobilinogen
Description
Bilirubin, blood, glucose, nitrites, protein, and urobilinogen measured as the number of milligrams per deciliter (mg/dL)
Time Frame
Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
Title
Safety endpoint - Change from baseline in urinalysis parameter ketones
Description
Ketones measured as the number of millimoles per liter (mmol/L)
Time Frame
Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
Title
Safety endpoint - Change from baseline in urinalysis parameter leukocyte esterase
Description
Leukocyte esterase measured as negative or positive; number of WBCs per high power field
Time Frame
Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
Title
Safety endpoint - Change from baseline in urinalysis parameter pH
Description
pH measured as pH units
Time Frame
Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
Title
Safety endpoint - Change from baseline in urinalysis parameter specific gravity
Description
Specific gravity measured as specific gravity units as a ratio of density of urine/density of water
Time Frame
Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
Title
Safety endpoint - Change from baseline in serum chemistry parameters globulin, protein, and albumin
Description
Globulin, protein, and albumin measured as grams per deciliter (g/dL)
Time Frame
Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
Title
Safety endpoint - Change from baseline in serum chemistry parameter alkaline phosphatase
Description
Alkaline phosphatase measured as International units per liter (IU/L)
Time Frame
Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
Title
Safety endpoint - Change from baseline in serum chemistry parameters bicarbonate, chloride, sodium, and magnesium
Description
Bicarbonate, chloride, sodium, and magnesium measured as milliequivalents per liter (mEq/L)
Time Frame
Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
Title
Safety endpoint - Change from baseline in serum calcium, glucose, phosphate, creatinine, urea, uric acid, bilirubin (conjugated and unconjugated), high density lipoproteins, low density lipoproteins, total bilirubin, total cholesterol
Description
Calcium, glucose, phosphate, creatinine, urea, uric acid, bilirubin (conjugated and unconjugated), high density lipoproteins, low density lipoproteins, total bilirubin, total cholesterol, triglycerides measured as milligrams per deciliter (mg/dL)
Time Frame
Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
Title
Safety endpoint - Change from baseline in serum chemistry parameters potassium
Description
Potassium measured as millimoles per liter (mmol/L)
Time Frame
Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
Title
Safety endpoint - Change from baseline in serum chemistry parameters lipase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, alanine aminotransferase, and amylase
Description
Lipase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, alanine aminotransferase, and amylase measured as Units per liter (U/L)
Time Frame
Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
Title
Safety endpoint - Change from baseline in virology parameters HIV-1/-2; HBsAg; HCV; SARS-COV-2
Description
HIV-1/-2; HBsAg; HCV; SARS-COV-2 test results measured as negative or positive
Time Frame
Baseline pre-intervention Day -28 to -2
Title
Safety endpoint - Change from baseline in drug screen findings for alcohol
Description
Alcohol test results measured as percentage (%)
Time Frame
Baseline pre-intervention Day -28 to -2; Day -1
Title
Safety endpoint - Change from baseline in urine drug screen findings for amphetamines, barbiturates, benzodiazepines, cocaine, cotinine, methamphetamines, opiates, phencyclidine, THC, and tricyclic antidepressants
Description
Urine amphetamines, barbiturates, benzodiazepines, cocaine, cotinine, methamphetamines, opiates, phencyclidine, THC, and tricyclic antidepressants test results measured as nanograms per milliliter (ng/mL)
Time Frame
Baseline pre-intervention Day -28 to -2; Day -1
Title
Safety endpoint - Change from baseline for pregnancy test for serum hCG and urine hCG
Description
Serum hCG and Urine hCG levels measured in milli-international units per liter (mIU/L)
Time Frame
Serum pregnancy test Days -28 to -2 and on Day 5; Urine pregnancy test Day -1
Title
Safety endpoint - Change from baseline for confirmation of postmenopausal status test for FSH
Description
FSH levels measured in milli-international units per liter (mIU/L)
Time Frame
Baseline pre-intervention on Days -28 to -2
Secondary Outcome Measure Information:
Title
Plasma pharmacokinetics - Cmax
Description
Plasma PRV-002 Cmax measured as microgram per mL (mcg/mL)
Time Frame
Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.
Title
Plasma pharmacokinetics - Tmax
Description
Plasma PRV-002 time to Cmax
Time Frame
Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.
Title
Plasma pharmacokinetics - area under the curve
Description
Plasma PRV-002 Area under the concentration-time curve from 0 to time of last quantifiable concentration (AUC0-t) measured as min*kBq/mL
Time Frame
Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.
Title
Plasma pharmacokinetics - area under the concentration-time curve
Description
Plasma PRV-002 area under the concentration-time curve from 0 to infinity (AUC0-inf) measured as mg*h/L
Time Frame
Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.
Title
Plasma pharmacokinetics - apparent terminal elimination half-life t1/2)
Description
Plasma PRV-002 apparent terminal elimination half-life (t1/2) measured in minutes or hours
Time Frame
Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.
Title
Plasma pharmacokinetics - terminal elimination rate constant (λz)
Description
Plasma PRV-002 terminal elimination rate constant (λz) measured as elimination rate measured as constant K or Ke ((λz))
Time Frame
Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.
Title
Plasma pharmacokinetics total apparent body clearance
Description
Plasma PRV-002 total apparent body clearance measured as (CL/F)
Time Frame
Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.
Title
Plasma pharmacokinetics - apparent volume of distribution
Description
Plasma PRV-002 apparent volume of distribution measured as (Vz/F)
Time Frame
Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.
Title
Urine pharmacokinetics - cumulative amount of unchanged drug excreted in urine
Description
Urine PRV-002 cumulative amount of unchanged drug excreted (Ae) in urine measured in micrograms per milliliter (mcg/mL)
Time Frame
Baseline pre-intervention on Day -1; Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24 hr.
Title
Urine pharmacokinetics - renal clearance
Description
Urine PRV-002 renal clearance measured as (CLr)
Time Frame
Baseline pre-intervention on Day -1; Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24 hr.
Other Pre-specified Outcome Measures:
Title
Exploratory endpoints - PRV-002 metabolites in plasma
Description
PRV-002 metabolites in plasma measured as micrograms per milliliter (mcg/mL)
Time Frame
Samples collected on Day 1, 2, and 5
Title
Nasal Spray Attributes Questionnaire
Description
Nasal Spray Attributes Questionnaire score, based on a scale of 0 to 6, for each immediate attribute assessed.
Time Frame
Nasal spray attributes questionare completed on Day 1 at 15 minutes post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
Adult males and females, 18 to 55 years of age (inclusive) at screening.
Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50 kg at screening.
Be non-smokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration.
Have a negative test for cotinine at the screening visit and at check-in on Day -1.
Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit in the Schedules of
Assessments (SoA), including:
Physical examination without any clinically significant findings
Systolic BP in the range of 90 to 160 mmHg (inclusive) and diastolic BP in the range of 50 to 95 mmHg (inclusive) after 5 minutes in supine position
Heart rate in the range of 40 to 100 bpm (inclusive) after 5 minutes rest in supine position
Body temperature (tympanic or oral) in the range 35.5°C to 37.7°C (inclusive)
No clinically significant findings in serum chemistry, haematology, coagulation, and urinalysis tests
Triplicate 12-lead ECG (taken after the volunteer has been supine for at least 5 minutes) with a QTcF ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities
Pulmonary assessments must be within the normal range (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC] and FEV1/FVC ratio ≥ 80% of normal values; f forced expiratory flow over the middle one half of the FVC [FEF25-75%] > 75% of predicted)
Oxygen saturation (SpO2) monitor ≥ 95%.
Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the timepoints indicated in the Schedules of Assessments (SoA), including:
Physical examination without any clinically significant findings
Systolic BP in the range of 90 to 160 mmHg (inclusive) and diastolic BP in the range of 50 to 95 mmHg (inclusive) after 5 minutes in supine position
Heart rate in the range of 40 to 100 bpm (inclusive) after 5 minutes rest in supine position
Body temperature (tympanic or oral) in the range 35.5°C to 37.7°C (inclusive)
No clinically significant findings in serum chemistry, haematology, coagulation, and urinalysis tests
Triplicate 12-lead ECG (taken after the volunteer has been supine for at least 5 minutes) with a QTcF ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities
Pulmonary assessments must be within the normal range (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC] and FEV1/FVC ratio ≥ 80% of normal values; f forced expiratory flow over the middle one half of the FVC [FEF25-75%] > 75% of predicted)
Oxygen saturation (SpO2) monitor ≥ 95%.
Female volunteers must:
Be of nonchildbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause
Have a follicle-stimulating hormone level >40 IU/L at the screening visit),or
If of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception from signing the consent form until at least 30 days after the last dose of the study drug.
Male volunteers must agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
Have suitable venous access for blood sampling.
Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
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Exclusion Criteria:
History or presence of significant cardiovascular disease
History or presence of significant pulmonary disease
History or presence of significant hepatic disease
History or presence of significant renal disease
History or presence of significant haematological disease
History or presence of significant gastrointestinal disease
History or presence of significant disease
History or presence of significant endocrine disease
History or presence of significant immunologic disease
History or presence of significant dermatologic disease
History or presence of significant or neurological disease
No major surgery within the past 3 months determined by the PI to be clinically significant.
Absence of any acute illness.
Current infection that requires systemically absorbed antibiotic.
Current infection that requires systemically absorbed antifungal.
Current infection that requires systemically absorbed antiparasitic.
Current infection that requires systemically absorbed antiviral medication.
Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration.
History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death).
Known arrythmia
Liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase, bilirubin (total, conjugated and unconjugated), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
Liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase
Liver function test results elevated more than 1.5-fold above the ULN for bilirubin (total)
Liver function test results elevated more than 1.5-fold above the ULN for bilirubin (conjugated)
Liver function test results elevated more than 1.5-fold above the ULN for ALP. Volunteers with ALP above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
Liver function test results elevated more than 1.5-fold above the ULN for AST. Volunteers with AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
Liver function test results elevated more than 1.5-fold above the ULN for ALT. Volunteers with ALT above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2) antibodies at the screening visit.
Positive test results for active hepatitis B surface antigen (HBsAg) antibodies at the screening visit.
Positive test results for active hepatitis C virus (HCV) antibodies at the screening visit.
Presence or having sequelae of known to interfere with the absorption, distribution, metabolism, or excretion of drugs such as gastrointestinal, liver, kidney, or other conditions .
Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN.
History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) within 12 weeks prior to the screening visit.
Positive drugs of abuse at the screening visit.
Positive drugs of abuse at check-in (Day -1).
Positive alcohol breath test results at the screening visit.
Positive alcohol breath test results at check-in (Day -1).
Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 10 days prior to the first study drug administration, - exceptions include use of contraceptives, occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days), ibuprofen (doses of 400 mg up to every 6 hours or 1.6 g per day maximum for no more than 3 consecutive days), topical ointments, and vitamins or dietary supplements.
Consumption of grapefruit or Seville orange (or products containing grapefruit or Seville orange) within 10 days prior to the first administration of study drug.
Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer's ability to participate in the trial.
Known hypersensitivity to any of the study drug ingredients.
Use of any vaccinations within 14 days prior to the first study drug administration.
For women of childbearing potential, a positive serum pregnancy test at the screening visit.
For women of childbearing potential, a positive urine pregnancy test (with confirmatory serum pregnancy test) at check-in (Day -1).
Females who are breastfeeding or planning to breast feed at any time during the study.
Donation of blood or plasma within 30 days prior to first study drug administration.
Loss of whole blood of more than 500 mL within 30 days prior to first study drug administration.
Receipt of a blood transfusion within 1 year of first study drug administration.
Participation in another clinical trial of an investigational drug within 60 days of the first study drug administration.
Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
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Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mike Lewandowski, BS
Phone
7276926196
Email
mlewandowski@odysseygi.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jake VanLandingham, PhD
Phone
850-544-2962
Email
jvanlandingham@odysseygi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philip Ryan, Dr.
Organizational Affiliation
Nucleus Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nucleus Network Pty Ltd,
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A First in Human Study of the Safety, Tolerability and Pharmacokinetics of PRV-002 in Healthy Volunteers
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