Clinical trial NCT02112110: Absolute Bioavailability of BMS-791325
Official title: Study of the Absolute Oral Bioavailability of BMS-791325 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C Virus Infection
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2014-04-11
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The purpose of this study is to determine the absolute bioavailability of 150 mg oral dose of BMS-791325 relative to 100 µg IV infusion of \[13C\]-BMS-791325.

Detailed description: Primary Purpose: Other: Protocol is designed to assess the absolute bioavailability of 150 mg (2x75 mg tablets) BMS-791325 administered orally

Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

1. Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
2. Men and women ages 18 to 49 years, inclusive
3. Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding

   * WOCBP and men who are sexually active with WOCBP must agree to follow protocol mandated instructions for method(s) of contraception during and after the study

Exclusion Criteria:

1. Any significant acute or chronic medical illness
2. Any current or recent gastrointestinal disease or surgery that could impact upon the absorption of study drug
3. Inability to tolerate oral medication
4. Inability to be venipunctured and/or tolerate venous access
5. Use of tobacco-containing or nicotine-containing products within 6 months
6. Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders (4th Edition)(DSM IV), Diagnostic Criteria for Drug and Alcohol Abuse
7. Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration at screening or Day -1, confirmed by repeat

i)PR ≥ 210 msec

ii)QRS ≥ 120 msec

iii)QT ≥ 500 msec

iv)QTcF ≥ 450 msec

v)Second or third degree heart block

h) Positive urine screen for drugs of abuse

i) Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, r HIV-1, -2 antibodies

j) Any of the following screening or Day -1 laboratory results outside the ranges specified below as defined by the laboratory, confirmed by repeat analysis:

i)Serum creatinine \> upper limit of normal (ULN)

ii)Alanine aminotransferase (ALT) \> ULN

iii)Aspartate aminotransferase(AST) \> ULN

iv)Total bilirubin \> ULN

k) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)

Primary outcomes:
measure: Absolute oral bioavailability (F) of BMS-791325
timeFrame: 48 hours from time of oral dosing
Secondary outcomes:
measure: Safety and tolerability of BMS-791325 by the occurrence of AEs and SAEs, abnormalities in vital sign measurements exceeding pre-defined thresholds, findings on ECGs and PEs, and abnormalities and marked abnormalities in clinical laboratory test.
timeFrame: Day 1 predose and 2 hours post-dose, Day 2 and Day 3
measure: Maximum observed plasma concentration (Cmax) of BMS-791325 (oral dose) and [13C]-BMS-791325 (IV dose)
timeFrame: Pre-dose and at 0.5, 1, 1.5, 1.75, 1.97, 2, 2.125, 2.25, 2.5, 2.75, 3, 4, 5, 6, 8, 10, 12, 16, 24, 28, 32, 36 and 48 hours post oral dose
measure: Time of maximum observed plasma concentration (Tmax) of BMS-791325 (oral dose) and [13C]-BMS-791325 (IV dose)
timeFrame: Pre-dose and at 0.5, 1, 1.5, 1.75, 1.97, 2, 2.125, 2.25, 2.5, 2.75, 3, 4, 5, 6, 8, 10, 12, 16, 24, 28, 32, 36 and 48 hours post oral dose
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) of BMS-791325 (oral dose) and [13C]-BMS-791325 (IV dose)
timeFrame: Pre-dose and at 0.5, 1, 1.5, 1.75, 1.97, 2, 2.125, 2.25, 2.5, 2.75, 3, 4, 5, 6, 8, 10, 12, 16, 24, 28, 32, 36 and 48 hours post oral dose
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-791325 (oral dose) and [13C]-BMS-791325 (IV dose)
timeFrame: Pre-dose and at 0.5, 1, 1.5, 1.75, 1.97, 2, 2.125, 2.25, 2.5, 2.75, 3, 4, 5, 6, 8, 10, 12, 16, 24, 28, 32, 36 and 48 hours post oral dose
measure: Terminal plasma half-life (T-HALF) of BMS-791325 (oral dose) and [13C]-BMS-791325 (IV dose)
timeFrame: Pre-dose and at 0.5, 1, 1.5, 1.75, 1.97, 2, 2.125, 2.25, 2.5, 2.75, 3, 4, 5, 6, 8, 10, 12, 16, 24, 28, 32, 36 and 48 hours post oral dose
measure: Total clearance (CLT) of [13C]-BMS-791325 (IV dose)
timeFrame: Pre-dose and at 0.5, 1, 1.5, 1.75, 1.97, 2, 2.125, 2.25, 2.5, 2.75, 3, 4, 5, 6, 8, 10, 12, 16, 24, 28, 32, 36 and 48 hours post oral dose
measure: Volume of distribution at steady-state (Vss) of [13C]-BMS-791325 (IV dose)
timeFrame: Pre-dose and at 0.5, 1, 1.5, 1.75, 1.97, 2, 2.125, 2.25, 2.5, 2.75, 3, 4, 5, 6, 8, 10, 12, 16, 24, 28, 32, 36 and 48 hours post oral dose
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Local Institution
state: Nottinghamshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: