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

Phase 1

Completed

• Conditions: Hepatitis C
• Interventions: Drug: Daclatasvir, Asunaprevir and BMS-791325 FDC; Drug: BMS-791325; Drug: Rosuvastatin

• Registration Number: NCT02104843
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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

Detailed Description

IND Number: 79,599/101,943

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

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-02
• Study First Submitted QC: 2014-04-02
• Study First Posted: 2014-04-04
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Status Verified: 2014-07
• Last Update Submitted: 2014-07-17
• Last Update Posted: 2014-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1: DCV/ASV/BMS-791325 FDC + BMS-791325 + Rosuvastatin	Daclatasvir, Asunaprevir and BMS-791325 FDC	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
Arm 1: DCV/ASV/BMS-791325 FDC + BMS-791325 + Rosuvastatin	BMS-791325	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
Arm 1: DCV/ASV/BMS-791325 FDC + BMS-791325 + Rosuvastatin	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

Primary Outcome Measures

Name	Time	Method
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)
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 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

Name	Time	Method
Half life (T-HALF) 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
Safety measured by incidence of Adverse events (AEs), Serious adverse events (SAEs) and AEs leading to discontinuation	Days 1 through 19
Apparent total body clearance (CLT/F) of Rosuvastatin	Days 1 and 15 (predose through 96 hours)
Time of maximum observed concentration (Tmax) of Rosuvastatin	Days 1 and 15 (predose through 96 hours)
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 results of vital sign measurements, Electrocardiogram (ECGs), physical examinations and clinical laboratory tests	Days 1 through 19