A Phase 1, Randomized, Double-Blind, Placebo-Controlled, First in Human Study of the Safety, Tolerability and Pharmacokinetics of PRV-002 in Healthy Volunteers.
Overview
- Phase
- Phase 1
- Intervention
- PRV-002
- Conditions
- Traumatic Brain Injury (TBI)
- Sponsor
- Odyssey Group International, Inc.
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Safety endpoint - Evaluation of the Incidence, severity, and relationship of AEs/SAEs (or ADEs/SADEs) (including withdrawals due to AEs (or ADEs)).
- Status
- Completed
- Last Updated
- last year
Overview
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 5 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. Cohorts 1 - 3 will receive a single dose of PRV-002 or placebo. Cohorts will receive one dose of PRV-002 or placebo per day for 5 consecutive days.
Investigators
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 -
- •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
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
Arms & Interventions
PRV-002
PRV-002 active formulation
Intervention: PRV-002
Placebo comparator
Placebo used is hydroxypropyl beta cyclodextrin (HPβCD)
Intervention: Placebo
Outcomes
Primary Outcomes
Safety endpoint - Evaluation of the Incidence, severity, and relationship of AEs/SAEs (or ADEs/SADEs) (including withdrawals due to AEs (or ADEs)).
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.
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)
Time Frame: Baseline pre-intervention Day -28 to -2.
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)
Time Frame: Baseline pre-intervention Day -1 and and Day 1; Day 2
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 respiration rate).
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
Respiration rate measured as breaths per minute
Safety endpoint - Change from baseline in vital signs (including changes from baseline in body temperature).
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
Body temperature measured as degrees Celsius (C)
Safety endpoint - Changes from baseline in lung spirometry.
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
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
Time Frame: Baseline pre-intervention; during intervention and immediately afterwards (Day 1); Day 2; and through Day 5.
Heart ratel measured beats per minute (BPM)
Safety endpoint - Change from baseline in ECG parameters of PR interval, QRS interval, and QT interval
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
PR interval, QRS interval, and QT interval as measured in milliseconds (ms)
Safety endpoint - Change from baseline in hematocrit values
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
Hematocrit measured as the percentage of red blood cells in whole blood (%)
Safety endpoint - Change from baseline in hemoglobin values
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
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
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
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.
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
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)
Time Frame: Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
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)
Time Frame: Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
Dihydrotestosterone (DHT) measured as the number of nano moles per liter (nmol/L) of blood
Safety endpoint - Change from baseline in vital signs (including changes from baseline in SpO2).
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
SpO2 measured as percent of oxygen (%)
Safety endpoint - Change from baseline in vital signs (including changes from baseline in blood pressure).
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
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).
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
Heart rate measured as beats per minute (BPM)
Safety endpoint - Change from baseline in the blood hormone level of luteinizing hormone (LH)
Time Frame: Baseline pre-intervention Days -28 to -2
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)
Time Frame: Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
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)
Time Frame: Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
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)
Time Frame: Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
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)
Time Frame: Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
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
Time Frame: Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
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)
Time Frame: Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5
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)
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
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
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
Fibrinogen measured as the number of milligrams per deciliter (mg/dL)
Safety endpoint - Change from baseline in the clotting factor International Normalized Ratio (INR)
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
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
Time Frame: Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
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
Time Frame: Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
Ketones measured as the number of millimoles per liter (mmol/L)
Safety endpoint - Change from baseline in urinalysis parameter leukocyte esterase
Time Frame: Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
Leukocyte esterase measured as negative or positive; number of WBCs per high power field
Safety endpoint - Change from baseline in urinalysis parameter pH
Time Frame: Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
pH measured as pH units
Safety endpoint - Change from baseline in urinalysis parameter specific gravity
Time Frame: Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr
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
Time Frame: Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
Globulin, protein, and albumin measured as grams per deciliter (g/dL)
Safety endpoint - Change from baseline in serum chemistry parameter alkaline phosphatase
Time Frame: Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
Alkaline phosphatase measured as International units per liter (IU/L)
Safety endpoint - Change from baseline in serum chemistry parameters bicarbonate, chloride, sodium, and magnesium
Time Frame: Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
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
Time Frame: Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
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
Time Frame: Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
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
Time Frame: Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.
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
Time Frame: Baseline pre-intervention Day -28 to -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
Time Frame: Baseline pre-intervention Day -28 to -2; Day -1
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
Time Frame: Baseline pre-intervention Day -28 to -2; Day -1
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
Time Frame: Serum pregnancy test Days -28 to -2 and on Day 5; Urine pregnancy test Day -1
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
Time Frame: Baseline pre-intervention on Days -28 to -2
FSH levels measured in milli-international units per liter (mIU/L)
Secondary Outcomes
- Plasma pharmacokinetics - Cmax(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.)
- Plasma pharmacokinetics - Tmax(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.)
- Plasma pharmacokinetics - area under the curve(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.)
- Plasma pharmacokinetics - area under the concentration-time curve(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.)
- Plasma pharmacokinetics - apparent terminal elimination half-life t1/2)(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.)
- Plasma pharmacokinetics - terminal elimination rate constant (λz)(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.)
- Plasma pharmacokinetics total apparent body clearance(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.)
- Plasma pharmacokinetics - apparent volume of distribution(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.)
- Urine pharmacokinetics - cumulative amount of unchanged drug excreted in urine(Baseline pre-intervention on Day -1; Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24 hr.)
- Urine pharmacokinetics - renal clearance(Baseline pre-intervention on Day -1; Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24 hr.)