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

Phase 1

Completed

• Conditions: Hepatitis C
• Interventions: Drug: DCV 3DAA FDC; Drug: BMS-791325

• Registration Number: NCT02108639
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

Assess the effect of renal function on the blood levels of DCV, ASV, 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 Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-07
• Study First Submitted QC: 2014-04-07
• Study First Posted: 2014-04-09
• Status Verified: 2014-06
• Primary Completion: 2014-06
• Study Completion: 2014-06
• Last Update Submitted: 2014-07-09
• Last Update Posted: 2014-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DCV 3DAA FDC + BMS-791325	DCV 3DAA FDC	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
DCV 3DAA FDC + BMS-791325	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Cmax fraction unbound (Cmaxfu) 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	BMS-948158 may also be analyzed
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
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
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
AUC(TAU) fraction unbound (AUC(TAU) fu) 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	BMS-948158 may also be analyzed
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
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 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
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
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
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
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

Trial Locations

Locations (4)

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

Clinical Pharmacology Of Miami Inc.; 🇺🇸 Miami, Florida, United States

Davita Clinical Research; 🇺🇸 Minneapolis, Minnesota, United States

New Orleans Center For Clinical Research - Knoxville; 🇺🇸 Knoxville, Tennessee, United States