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

Ebola Virus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02319772
• Other study ID #: BCX4430-101
• Secondary ID: DMID 14-0030
• Status: Completed
• Phase: Phase 1
• First received: December 11, 2014
• Last updated: July 6, 2016
• Start date: December 2014
• Est. completion date: April 2016

Study information

• Verified date: July 2016
• Source: BioCryst Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: April 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Weight = 50 kg (110 lbs) and = 100 kg (220 lbs)

2. Body mass index (BMI) of 19-32 kg/m2

3. Willing to abstain from alcohol consumption for a period of 2 days prior to and during the study

4. Sexually active women of child bearing potential and sexually active men must utilize 2 highly effective contraceptive methods

5. Abstain from caffeinated beverages

6. Normal vital signs at rest

7. Ability to provide written informed consent

Exclusion Criteria:

1. Subjects who are study site employees, or immediate family members of a study site or sponsor employee

2. Participation in a clinical research study within the previous 90 days

3. 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

4. Any screening laboratory test with an abnormal result that is grade 1 (mild) or greater

5. 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

6. 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

7. Family or personal history of sudden death or QT prolongation

8. 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

9. Inadequate muscle mass to receive IM injections

10. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse

11. Current smokers or history of smoking within the last 12 months

12. Serious adverse reaction or serious hypersensitivity to any drug

13. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active

14. Donation or loss of greater than 400 mL of blood within the previous 3 months

15. Positive serology for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) type 1

16. Pregnant or nursing females

17. Male subjects with pregnant female partners

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• Ebola Virus Infection
• Filovirus Infections
• Hemorrhagic Fever, Ebola
• Infection
• Virus Diseases

Intervention

Drug:
• BCX4430

• Placebo

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical	Ruddington

Sponsors (2)

Lead Sponsor	Collaborator
BioCryst Pharmaceuticals	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The levels of BCX6870, the triphosphate metabolite of BCX4430, in peripheral blood mononuclear cells following single (Part 1) and multiple (Part 2) doses of BCX4430		Part 1: 7 days. Part 2: 14 days	No
Primary	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	Yes
Secondary	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	No
Secondary	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	No