Drug Interaction Between Daclatasvir/Asunaprevir/BMS-791325 and Rosuvastatin

Effect of Daclatasvir/Asunaprevir/BMS-791325 Three Drug Antiviral Combination Therapy on the Pharmacokinetics of Rosuvastatin

The primary purpose is to assess the effect of Daclatasvir (DCV)/Asunaprevir (ASV)/BMS-791325 combination therapy on the exposure of Rosuvastatin.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Rosuvastatin; Drug: BMS-791325; Drug: Daclatasvir, Asunaprevir and BMS-791325 FDC

Detailed Description

IND Number: 79,599/101,943

Primary Purpose: Other - Phase 1 Clinical Pharmacology drug interaction study in healthy subjects

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Inclusion Criteria:

• Healthy subjects with no clinically significant deviations from normal in medical history, physical exam findings, 12 lead ECG measurements and clinical laboratory tests
• Females must be of non-childbearing potential

Exclusion Criteria:

• Women of childbearing potential
• Any significant acute or chronic medical condition
• Inability to tolerate oral medications
• Inability to be venipunctured and/or tolerate venous access
• Abnormal liver function tests
• Current or recent (within 3 months of dosing) gastrointestinal disease

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: DCV/ASV/BMS-791325 FDC + BMS-791325 + Rosuvastatin; Treatment A: Rosuvastatin tablet orally on specified days Treatment B: Daclatasvir, Asunaprevir and BMS-791325 Fixed dose combination (FDC) + BMS-791325 tablet orally on specified days Treatment C: Daclatasvir, Asunaprevir and BMS-791325 FDC + BMS-791325 + Rosuvastatin tablet orally on specified days	Drug: Rosuvastatin; Other Names: Crestor®; Drug: BMS-791325; Drug: Daclatasvir, Asunaprevir and BMS-791325 FDC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax) of Rosuvastatin	Day 1 (predose) to Day 5 (96 hours) and Day 15 (predose) to Day 19 (96 hours)
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T)) of Rosuvastatin	Day 1 (predose) to Day 5 (96 hours) and Day 15 (predose) to Day 19 (96 hours)
Area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of Rosuvastatin	Day 1 (predose) to Day 5 (96 hours) and Day 15 (predose) to Day 19 (96 hours)

Secondary Outcome Measures

Outcome Measure	Time Frame
Time of maximum observed concentration (Tmax) of Rosuvastatin	Days 1 and 15 (predose through 96 hours)
Half life (T-HALF) of Rosuvastatin	Days 1 and 15 (predose through 96 hours)
Apparent total body clearance (CLT/F) of Rosuvastatin	Days 1 and 15 (predose through 96 hours)
Maximum observed concentration (Cmax) of Daclatasvir, Asunaprevir and BMS-791325 and BMS-794712	Day 15 (predose through 12 hours) and Days 13 and 14 pre-AM-dose
Trough observed plasma concentration (predose) (Ctrough) of Daclatasvir, Asunaprevir and BMS-791325 and BMS-794712	Day 15 (predose through 12 hours) and Days 13 and 14 pre-AM-dose
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of Daclatasvir, Asunaprevir and BMS-791325 and BMS-794712	Day 15 (predose through 12 hours) and Days 13 and 14 pre-AM-dose
Time of maximum observed concentration (Tmax) of Daclatasvir, Asunaprevir and BMS-791325 and BMS-794712	Day 15 (predose through 12 hours) and Days 13 and 14 pre-AM-dose
Observed plasma concentration at 12 hours after dosing in a pharmacokinetic (PK) profile (C12) of Daclatasvir, Asunaprevir and BMS-791325 and BMS-794712	Day 15 (predose through 12 hours) and Days 13 and 14 pre-AM-dose
Safety measured by incidence of Adverse events (AEs), Serious adverse events (SAEs) and AEs leading to discontinuation	Days 1 through 19
Safety measured by results of vital sign measurements, Electrocardiogram (ECGs), physical examinations and clinical laboratory tests	Days 1 through 19

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (Estimate): April 4, 2014

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Asunaprevir
• Other Study ID Numbers: AI443-115