Study to Determine the Potential DDIs When the Daclatasvir/Asunaprevir/BMS-791325 Three Drug Antiviral Combination Tablet (FDC) is Coadministered With a Cocktail of Cytochrome P450 (CYP) Probe Substrates and Transporter Probe Substrates (Digoxin and Pravastatin) in Healthy Subjects
Information source: Bristol-Myers Squibb
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatitis C
Intervention: Cocktail (Drug); DCV 3DAA FDC (Drug); BMS-791325 (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Bristol-Myers Squibb Official(s) and/or principal investigator(s): Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb
Summary
The primary purpose of this study is to assess the effect of the
Daclatasvir/Asunaprevir/BMS-791325 fixed dose combination (FDC) tablet on the
pharmacokinetics of the cocktail CYP and transporter probe substrates and to assess the
effect of the DCV 3DAA FDC [DCV 3DAA FDC = fixed dose combination formulation of 3
direct-acting antivirals (3DAA) (DCV 30 mg, ASV 200 mg, and BMS-791325 75 mg)] + BMS-791325
75-mg single-agent tablet on the Pharmacokinetic (PK) of the cocktail CYP and transporter
probe substrates.
Clinical Details
Official title: Effect of a Fixed Dose Combination Formulation of Daclatasvir/Asunaprevir/BMS-791325 on the Pharmacokinetics of a Cocktail of CYP Probe Substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, and Midazolam) and Transporter Probe Substrates (Digoxin and Pravastatin) in Healthy Subjects
Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label
Primary outcome: Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] for each cocktail CYP and transporter probe substrate
Secondary outcome: Maximum observed concentration (Cmax) for each cocktail CYP and transporter probe substrateArea under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] for each cocktail CYP and transporter probe substrate Cmax for the measured metabolites of the cocktail CYP and transporter probe substrates AUC(0-T) for the measured metabolites of the cocktail CYP and transporter probe substrates AUC(INF) for the measured metabolites of the cocktail CYP and transporter probe substrates Time of maximum observed concentration (Tmax) for each cocktail CYP and transporter probe substrate and their metabolites Half life (T-HALF) for each cocktail CYP and transporter probe substrate and their metabolites Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) for each cocktail CYP and transporter probe substrate and their metabolites Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)] for each cocktail CYP and transporter probe substrate and their metabolites Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] for each cocktail CYP and transporter probe substrate and their metabolites Apparent total body clearance (CLT/F) for each cocktail CYP and transporter probe substrate Cmax for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state Tmax for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state Concentration at 12 hours (C12) for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state Area under the concentration-time curve in one dosing interval [AUC(TAU)] for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state MR_Cmax for BMS-791325 and the metabolite, BMS-794712 Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] for BMS-791325 and the metabolite, BMS-794712 Trough observed plasma concentration (Ctrough) for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS-794712 Safety measured by the occurrence of AEs and SAEs, abnormalities in vital sign measurements exceeding pre-defined thresholds, findings on ECG measurements and physical examinations, and marked abnormalities in clinical laboratory test results
Detailed description:
IND number: 79,599 and 101,943
Primary purpose: Other: study is being conducted to investigate the potential drug-drug
interactions (DDIs) when the Daclatasvir/Asunaprevir/BMS-791325 FDC formulation is
coadministered with a cocktail of cytochrome P450 (CYP) probe substrates (Caffeine,
Metoprolol, Montelukast, Flurbiprofen, Omeprazole, and Midazolam) and transporter probe
substrates (Digoxin and Pravastatin) in healthy subjects. It is also intended to
characterize the PK of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325, and its major
metabolite, BMS-794712, at steady state.
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
Criteria:
For more information regarding BMS clinical trial participation, please visit
www. BMSStudyConnect. com
Inclusion Criteria:
- Healthy subjects as determined by no clinically significant deviation from normal in
medical history, physical examinations, vital sign measurements, 12-lead ECG
measurements, and clinical laboratory test results
- Body mass index (BMI) of 18. 0 to 32. 0 kg/m2, inclusive. BMI = weight (kg)/[height
(m)]2
- Men and women, ages 18 to 45 years, inclusive
- Women must not be of childbearing potential, must not be breastfeeding
Exclusion Criteria:
- Any significant acute or chronic medical illness
- History of important arrhythmias including, but not limited to, ventricular
fibrillation, ventricular tachycardia, complete atrioventricular (A-V) block,
Wolff-Parkinson-White syndrome
- History of cardiac arrhythmias or palpitations associated with presyncope or syncope,
or history of unexplained syncope
- History of heart disease
- History of prolonged QT interval or torsades de pointes (TdP)
- History of hypokalemia
- Family history of sudden cardiac death at a young age, TdP, or Long QT syndrome
- History of asthma, bronchospasm, or sleep apnea
- History of rhabdomyolysis
- History of a bleeding disorder
- History of Raynaud's disease
- History of peptic ulcer disease or significant gastrointestinal bleed
- History of biliary disorders, including Gilbert's disease or Dubin-Johnson disease
- Current or recent (within 3 months of study drug administration) gastrointestinal
disease
- Any major surgery within 4 weeks of study drug administration
- Any gastrointestinal surgery (including cholecystectomy) that could impact upon the
absorption of study drug
Locations and Contacts
Additional Information
Starting date: February 2014
Last updated: June 16, 2014
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