Clinical trial NCT02108639: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2014-04-09
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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)

Eligibility criteria: 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

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax) for DCV, ASV, BMS-791325 and BMS-794712
timeFrame: For Groups A-D: Day 1 to Day 10 and for Group E: Day 1 to Day 12
measure: Area under the concentration-time curve in 1 dosing interval (AUC(TAU)) for DCV, ASV, BMS-791325 and BMS-794712
timeFrame: For Groups A-D: Day 1 to Day 10 and for Group E: Day 1 to Day 12
Secondary outcomes:
measure: Concentration at 12 hours (C12) for (DCV, ASV, BMS-791325) and BMS-948158
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Time of maximum observed concentration (Tmax) for (DCV, ASV, BMS-791325) and BMS-948158
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Apparent total body clearance (CLT/F) for (DCV, ASV and BMS-791325 only)
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Trough observed plasma concentration (Ctrough) for (DCV, ASV, BMS-791325), BMS-794712 and BMS-948158
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Cmax fraction unbound (Cmaxfu) for (DCV, ASV, BMS-791325), BMS-794712 and BMS-948158
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: AUC(TAU) fraction unbound (AUC(TAU) fu) for (DCV, ASV, BMS-791325), BMS-794712 and BMS-948158
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Protein Binding for DCV, ASV, BMS-791325 and BMS-794712
timeFrame: 1 and 4 hours postdose on Day 10 (all subjects) and Day 12 (Group E only)
measure: Total amount recovered in urine (URt) for (DCV, ASV, BMS-791325) and BMS-794712
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Total percent of administered dose recovered in urine (%URt) for (DCV, ASV, and BMS-791325 only)
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Renal clearance (CLR) for DCV, ASV, BMS-791325, and BMS-794712
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Maximum observed concentration (Cmax) for BMS-948158
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Area under the concentration-time curve in 1 dosing interval (AUC (TAU)) for BMS-948158
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Safety based on occurrence of Adverse Event (AEs), Serious adverse event (SAEs) and AEs leading to discontinuation
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Safety based on abnormalities in vital sign measurements
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Safety based on findings on ECG measurements and physical examinations
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
measure: Safety based on Marked abnormalities in clinical laboratory test findings
timeFrame: For Groups A-D: Day 1 to Day 11 and for Group E: Day 1 to Day 13
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology Of Miami Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Minneapolis
country: United States
facility: Davita Clinical Research
state: Minnesota
city: Knoxville
country: United States
facility: New Orleans Center For Clinical Research - Knoxville
state: Tennessee
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: