A Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BCX4430

Study Overview
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Brief Summary
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This is a 2-part, first-in-human dose-ranging study to evaluate the safety, tolerability and pharmacokinetics of escalating doses of BCX4430 administered via intramuscular (IM) injection in healthy subjects. In part 1, subjects will receive a single dose of BCX4430; in part 2 subjects will receive BCX4430 for 7 days.

Detailed Description
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Part 1 of the study will evaluate the safety, tolerability and pharmacokinetics of single, ascending doses of BCX4430 versus placebo in healthy subjects. Up to 6 ascending dose cohorts will be enrolled in a sequential manner. Eight subjects will be treated with a single dose of study drug per dose cohort: 6 subjects per cohort will receive BCX4430, and 2 subjects per cohort will receive matching placebo. Part 2 of the study will be initiated following review of all available data from Part 1 by an independent Safety Monitoring Committee Part 2 of the study will evaluate the safety, tolerability, and pharmacokinetics of 7 days of daily dosing with BCX4430 versus placebo in healthy subjects. Up to 4 ascending dose cohorts will be treated in a sequential manner. Ten subjects will be treated with study drug per dose cohort (8 subjects will receive BCX4430 and 2 subjects will receive placebo per cohort). The planned doses and dosing regimens for each of the Part 2 cohorts will be determined based upon data collected during Part 1.

Official Title
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A Phase 1 Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BCX4430 Administered Via Intramuscular Injection (IM) in Healthy Subjects

Conditions
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Filovirus Infections, Ebola Virus Infection

Intervention / Treatment
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* Drug: BCX4430
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weight ≥ 50 kg (110 lbs) and ≤ 100 kg (220 lbs) Body mass index (BMI) of 19-32 kg/m2 Willing to abstain from alcohol consumption for a period of 2 days prior to and during the study Sexually active women of child bearing potential and sexually active men must utilize 2 highly effective contraceptive methods Abstain from caffeinated beverages Normal vital signs at rest Ability to provide written informed consent Exclusion Criteria: Subjects who are study site employees, or immediate family members of a study site or sponsor employee Participation in a clinical research study within the previous 90 days Any medical condition or medical history that, in the opinion of the investigator or sponsor, would interfere with the subject's ability to participate in the study or increase the risk of participation for that subject Any screening laboratory test with an abnormal result that is grade 1 (mild) or greater Abnormal ECG (defined as any screening or baseline QTc>450 msec, PR > 200 msec, or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping An abnormal cardiovascular exam including a confirmed elevated blood pressure at screening (systolic greater than 140, diastolic greater than 90) after 5 minutes of supine rest, tachycardia >100 bpm after 5 minutes of supine rest Family or personal history of sudden death or QT prolongation Use of prescription, over-the-counter (OTC) medications or herbal supplements, with the exception of acetaminophen and non-oral hormonal contraception, for a period of 7 days prior to and during the study Inadequate muscle mass to receive IM injections History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse Current smokers or history of smoking within the last 12 months Serious adverse reaction or serious hypersensitivity to any drug Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active Donation or loss of greater than 400 mL of blood within the previous 3 months Positive serology for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) type 1 Pregnant or nursing females Male subjects with pregnant female partners

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCX4430<br>BCX4430 administered as an IM injection | Drug: BCX4430<br> <br> |
| Placebo Comparator: Placebo<br>Matched placebo administered as an IM injection | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, measured by the frequency and severity of adverse events, laboratory abnormalities and other safety parameters following single (Part 1) and multiple (Part 2) doses of BCX4430 | Evaluation of the incidence and severity of adverse events, laboratory abnormalities, ECG findings, vital sign changes, injection site and physical examination findings | Part 1: 7 days. Part 2: 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma exposure of BCX4430, determined by the concentration time profile and PK parameters following single (Part 1) and multiple (Part 2) doses of BCX4430 |  | Part 1: 7 days. Part 2: 14 days | 
| The urinary elimination of BCX4430, determined by the concentration of drug following single (Part 1) and multiple (Part 2) doses of BCX4430 |  | Part 1: 7 days. Part 2: 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers, Ebola virus, Filovirus