To Assess the Effect of Renal Impairment on the Blood Levels of Daclatasvir (DCV), Asunaprevir (ASV) and BMS-791325 After Multiple Doses of a Fixed Dose Combination Tablet

An Open-label, Multiple-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Fixed Dose Combination Formulation of DCV, ASV, and BMS-791325 in Subjects With Normal Renal Function and Subjects With Mild, Moderate, Severe, and End-stage Renal Dysfunction

Assess the effect of renal function on the blood levels of DCV, ASV, BMS-791325.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: DCV 3DAA FDC; Drug: BMS-791325

Detailed Description

IND Number: 79,599/101,943

Primary Purpose: Other - Phase 1 Clinical Pharmacology study to determine the effect of renal impairment on the exposure of DCV, ASV, BMS-791325 (fixed dosed combination) and BMS-791325 given in multiple doses

Fixed dose combination (FDC)

Fixed Dose Combination of Daclatasvir, Asunaprevir and BMS-791325 (DCV 3DAA FDC)

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology Of Miami Inc.
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Davita Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center For Clinical Research - Knoxville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Inclusion Criteria:

• Subjects in Group A must be in good health and have normal renal function
• Subjects in Groups B-E may have clinical, Electrocardiogram (ECG) and laboratory findings consistent with their degree of renal dysfunction
• Women of childbearing potential (WOCBP) and male participants must agree to follow the required contraceptive methods

Exclusion Criteria:

• Subjects in Group A must not have any significant acute or chronic illnesses
• Subjects in Groups B-E must not have uncontrolled or unstable cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematopoietic, and/or neurological disease within 6 months of screening
• Subjects in Groups B-E may not have evidence of rapidly deteriorating renal function, defined as a screening creatinine clearance (CLcr) which has decreased from a previous CLcr by 50% within the last 3 months
• Prior exposure to DCV, ASV or BMS-791325 within 3 months prior to study drug administration

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: DCV 3DAA FDC + BMS-791325; Group A to D: DCV 3DAA FDC + BMS-791325 oral tablets on specific days Group E: DCV 3DAA FDC + BMS-791325 oral tablets on specific days	Drug: DCV 3DAA FDC; Other Names: Fixed Dose Combination of Daclatasvir, Asunaprevir and BMS-791325; Drug: BMS-791325

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration (Cmax) for DCV, ASV, BMS-791325 and BMS-794712	For Groups A-D: Day 1 to Day 10 and for Group E: Day 1 to Day 12
Area under the concentration-time curve in 1 dosing interval (AUC(TAU)) for DCV, ASV, BMS-791325 and BMS-794712	For Groups A-D: Day 1 to Day 10 and for Group E: Day 1 to Day 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration at 12 hours (C12) for (DCV, ASV, BMS-791325) and BMS-948158		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Time of maximum observed concentration (Tmax) for (DCV, ASV, BMS-791325) and BMS-948158		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Apparent total body clearance (CLT/F) for (DCV, ASV and BMS-791325 only)		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Trough observed plasma concentration (Ctrough) for (DCV, ASV, BMS-791325), BMS-794712 and BMS-948158		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Cmax fraction unbound (Cmaxfu) for (DCV, ASV, BMS-791325), BMS-794712 and BMS-948158	BMS-948158 may also be analyzed	For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
AUC(TAU) fraction unbound (AUC(TAU) fu) for (DCV, ASV, BMS-791325), BMS-794712 and BMS-948158	BMS-948158 may also be analyzed	For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Protein Binding for DCV, ASV, BMS-791325 and BMS-794712		1 and 4 hours postdose on Day 10 (all subjects) and Day 12 (Group E only)
Total amount recovered in urine (URt) for (DCV, ASV, BMS-791325) and BMS-794712		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Total percent of administered dose recovered in urine (%URt) for (DCV, ASV, and BMS-791325 only)		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Renal clearance (CLR) for DCV, ASV, BMS-791325, and BMS-794712		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Maximum observed concentration (Cmax) for BMS-948158		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Area under the concentration-time curve in 1 dosing interval (AUC (TAU)) for BMS-948158		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Safety based on occurrence of Adverse Event (AEs), Serious adverse event (SAEs) and AEs leading to discontinuation		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Safety based on abnormalities in vital sign measurements		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Safety based on findings on ECG measurements and physical examinations		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Safety based on Marked abnormalities in clinical laboratory test findings		For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 7, 2014
• First Submitted That Met QC Criteria: April 7, 2014
• First Posted (Estimate): April 9, 2014

Study Record Updates

• Last Update Posted (Estimate): July 10, 2014
• Last Update Submitted That Met QC Criteria: July 9, 2014
• Last Verified: June 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; Protease Inhibitors; Asunaprevir
• Other Study ID Numbers: AI443-110

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No