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

NCT02045966 | Completed Phase 1

• 1 other identifier: AI443-021
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] for each cocktail CYP and transporter probe substrate

  51 time points up to day 36

Secondary Outcomes (19)

• Maximum observed concentration (Cmax) for each cocktail CYP and transporter probe substrate

  51 time points up to day 36

• Area 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

  51 time points up to day 36

• Cmax for the measured metabolites of the cocktail CYP and transporter probe substrates

  51 time points up to day 36

• AUC(0-T) for the measured metabolites of the cocktail CYP and transporter probe substrates

  51 time points up to day 36

• AUC(INF) for the measured metabolites of the cocktail CYP and transporter probe substrates

  51 time points up to day 36

Study Arms (1)

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

EXPERIMENTAL

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

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

Interventions

Cocktail DRUG

Cocktail = Caffeine 200 mg, Metoprolol 50 mg, Montelukast 10 mg, Flurbiprofen 50 mg, Omeprazole 40 mg, Midazolam 5 mg, Digoxin 0.25 mg, and Pravastatin 40 mg

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

DCV 3DAA FDC DRUG

DCV 30 mg + ASV 200 mg + BMS-791325 75 mg

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

BMS-791325 DRUG

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

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

MeSH Terms

Conditions

Hepatitis C

Interventions

8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2014
• First Posted: January 27, 2014
• Study Start: February 1, 2014
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: June 17, 2014

Record last verified: 2014-06