Phase I, Escalating, Multiple-Dose, ST-246 Safety, Tolerability and Pharmacokinetics 21-Day Trial in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of a single, daily, oral dose of ST-246 (either 250, 400 or 800mg) administered for 21 days to 30 healthy, fed volunteers.

Detailed Description
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This was a double-blind, placebo-controlled, dose-escalating, multiple-dose study of orally administered ST-246 to 30 healthy volunteers ages 18-50 years, randomized to receive either active drug (8 subjects) or placebo (2 subjects) in 1 of 3 dosing groups (250, 400 or 800mg groups). Each dose group of 10 was divided into two cohorts of 5 subjects (4 active and 1 placebo). The first cohort was dosed approximately 4-8 weeks before the second cohort of each dose group. Dose groups completed the study treatment approximately 5 weeks prior to the start of the following dose group. Study procedures included several overnight stays, medical history/exam, laboratory testing done by blood draw, and electrocardiograms.

Official Title
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Double-blind, Randomized, Placebo-controlled, Escalating, Multiple-dose, Phase I Trial to Assess Safety, Tolerability and Pharmacokinetics of ST-246 Administered as a Single Daily Dose for 21 Days in Healthy, Non-fasted Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: ST-246
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Subject Inclusion Criteria: Healthy volunteers Ability to Consent Not taking any other medication Adequate venous access Using adequate birth control Subject Exclusion Criteria: Inability to swallow study medication. Pregnant or breastfeeding Received experimental drug within 30 days of study entry or will participate in any experimental study during the study period. Current drug abuse, alcohol abuse, or homelessness. Taking concomitant medication Lactose Intolerance Medical condition; e.g., asthma, diabetes, thyroid disease, angioedema, BMI >35 or <18, hypertension, bleeding disorder, malignancy, seizure, neutropenia, Hepatitis B or C, HIV or AIDS. Any condition, occupational reason or other responsibility that, in the judgment of the Investigator, would jeopardize the safety or rights of a volunteer, or render the subject unable to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ST-246<br>250 mg, 400 mg or 800 mg of ST-246 given once daily for 21 days | Drug: ST-246<br>* 250 mg, 400 mg or 800 mg capsules given once daily for 21 days<br>* Other names: Tecovirimat;|
| Placebo Comparator: placebo<br>Placebo to match ST-246 | Drug: Placebo<br>* Capsules to match experimental drug<br>* Other names: Placebo to match ST-246;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Study Participants Who Tolerated ST-246 (250, 400 or 800mg) as Determined by Changes in Safety Parameters, According to the Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Events (AE) Grading Table | Evaluated safety parameters included: physical examination/vital signs electrocardiograms (heart rate, PR interval, QRS duration, QT interval, and QTc Bazett) laboratory safety tests (hematology, chemistry, urinalysis) adverse events (AEs) For a)-c), statistical values (mean, standard deviation, median, minimum, maximum) and changes from baseline (Day 1 pre-dose) to each time-point, were compared to laboratory normal reference ranges. If values for a)-d) were a Grade 3 or higher (in DAIDS AE Table)and ST-246-related, they were considered severe and significant, respectively. | Days 1, 6, 14-16, 21-24, 28-31, and 51-53 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax | Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data | Day 1 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax | Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data | Day 6 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax | Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data | Day 21 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax | Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles. | Day 1 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax | Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles. | Day 6 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax | Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles. | Day 21 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: t½ | t½: Observed terminal elimination half-life determined after the last dose on Day 21 | Day 21 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau | AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule | Day 1 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau | AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule | Day 6 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau | AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule | Day 21 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Ae(0-24) | Ae(0-24): Cumulative amount of drug excreted unchanged in urine over 24 hours (three 8-hour collection periods), determined on Days 1 and 21 | Day 1 | 
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Ae(0-24) | Ae(0-24): Cumulative amount of drug excreted unchanged in urine over 24 hours (three 8-hour collection periods), determined on Days 1 and 21 | Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers