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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Hepatitis C

Treatments: Drug: Cocktail; Drug: DCV 3DAA FDC; Drug: BMS-791325

Study type: Interventional

Funder types: Industry

Identifiers

NCT02045966

AI443-021

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

16 participants in 1 patient group

Arm 1: Cocktail + DCV 3DAA FDC + BMS-791325

Experimental group

Description:

Treatment A: Cocktail of CYP and transporter probe substrates orally as a single dose on Day 1 Treatment B: DCV 3DAA FDC tablet administered orally BID on Days 6 to 15 Treatment C: DCV 3DAA FDC tablet administered orally BID on Days 16 to 20, plus the cocktail of CYP and transporter probe substrates administered orally as a single dose on Day 16 only Treatment D: DCV 3DAA FDC tablet plus BMS-791325 75-mg single-agent tablet administered orally BID on Days 21 to 30 Treatment E: DCV 3DAA FDC tablet plus BMS-791325 75-mg single-agent tablet administered orally BID on Days 31 to 35, plus the cocktail of CYP and transporter probe substrates administered orally as a single dose on Day 31 only

Treatment:

Drug: Cocktail

Drug: DCV 3DAA FDC

Drug: BMS-791325