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Completed

NCT Number: NCT02045966

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

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.

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Key information

Conditions

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

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

DCV 3DAA FDC

Drug

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

BMS-791325

Drug

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

    Time frame: 51 time points up to day 36

Secondary outcomes

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

    Time frame: 51 time points up to day 36

  2. 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

    Time frame: 51 time points up to day 36

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

    Time frame: 51 time points up to day 36

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

    Time frame: 51 time points up to day 36

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

    Time frame: 51 time points up to day 36

  6. Time of maximum observed concentration (Tmax) for each cocktail CYP and transporter probe substrate and their metabolites

    Time frame: 51 time points up to day 36

  7. Half life (T-HALF) for each cocktail CYP and transporter probe substrate and their metabolites

    Time frame: 51 time points up to day 36

  8. Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) for each cocktail CYP and transporter probe substrate and their metabolites

    Time frame: 51 time points up to day 36

  9. 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

    Time frame: 51 time points up to day 36

  10. 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

    Time frame: 51 time points up to day 36

  11. Apparent total body clearance (CLT/F) for each cocktail CYP and transporter probe substrate

    Time frame: 51 time points up to day 36

  12. Cmax for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state

    Time frame: 24 time points up to day 31

  13. Tmax for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state

    Time frame: 24 time points up to day 31

  14. Concentration at 12 hours (C12) for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state

    Time frame: 24 time points up to day 31

  15. 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

    Time frame: 24 time points up to day 31

  16. MR_Cmax for BMS-791325 and the metabolite, BMS-794712

    Time frame: 24 time points up to day 31

  17. Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] for BMS-791325 and the metabolite, BMS-794712

    Time frame: 24 time points up to day 31

  18. Trough observed plasma concentration (Ctrough) for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS-794712

    Time frame: 24 time points up to day 31

  19. 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

    Time frame: Up to day 36

    AEs = Adverse events

    SAEs = Serious Adverse events

    ECG = Electrocardiogram

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2014
Study completion
2014
First posted
Jan 27, 2014
Registry last updated
Jun 17, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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