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

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

Detailed Description
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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)

Official Title
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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

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: DCV 3DAA FDC
* Drug: BMS-791325


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DCV 3DAA FDC + BMS-791325<br>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<br> <br> * Other names: Fixed Dose Combination of Daclatasvir, Asunaprevir and BMS-791325;Drug: BMS-791325<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |