Study of the Pharmacokinetics and Safety of Asunaprevir in Patients With Kidney Disease

Study Overview
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Brief Summary
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The purpose of the study is to determine how Asunaprevir is handled by the body of subjects with kidney disease compared with subjects with normal kidney function

Detailed Description
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Primary Purpose: Other: The purpose of the study is to determine how Asunaprevir is handled by the body of subjects with kidney disease compared with subjects with normal kidney function

Official Title
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Open-Label, Parallel Group, Multiple-Dose Study to Evaluate the Pharmacokinetics and Safety of Asunaprevir in Subjects With Renal Function Impairment

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Asunaprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group A: Subjects with normal renal function Group B: Patients with end stage renal disease Group C: Patients with mild renal impairment Group D: Patients with moderate renal impairment Group E: Patients with severe renal impairment Exclusion Criteria: History of uncontrolled or unstable cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematopoietic, psychiatric and/or neurological disease Hepatitis B or C Human Immunodeficiency Virus (HIV) Recent gastrointestinal disease

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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Subjects with normal renal function<br>Asunaprevir 100 mg tablet by mouth twice daily for 7 days | Drug: Asunaprevir<br> <br> * Other names: BMS-650032;|
| Experimental: Arm B: Subjects with end stage renal disease<br>Asunaprevir 100 mg tablet by mouth twice daily for 7 days | Drug: Asunaprevir<br> <br> * Other names: BMS-650032;|
| Experimental: Arm C: Subjects with mild renal impairment<br>Asunaprevir 100 mg tablet by mouth twice daily for 7 days | Drug: Asunaprevir<br> <br> * Other names: BMS-650032;|
| Experimental: Arm D: Subjects with moderate renal impairment<br>Asunaprevir 100 mg tablet by mouth twice daily for 7 days | Drug: Asunaprevir<br> <br> * Other names: BMS-650032;|
| Experimental: Arm E: Subjects with severe renal impairment<br>Asunaprevir 100 mg tablet by mouth twice daily for 7 days | Drug: Asunaprevir<br> <br> * Other names: BMS-650032;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(TAU) of Asunaprevir assessed using plasma concentrations on Day 7 | Area under the concentration-time curve in one dosing interval [AUC(TAU)] will be calculated from the blood drug concentration versus time curve | 11 time points on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma protein binding (PB) of Asunaprevir will be determined from the 1 hour and 3 hour time points post-dose |  | 1 and 3 hours of Day 7 | 
| Maximum observed plasma concentration (Cmax) of Asunaprevir | Pharmacokinetic (PK) parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Unbound Maximum observed plasma concentrations (Cmaxu) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Time of maximum observed plasma concentration (Tmax) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Minimum observed plasma concentration at one dose interval (C12) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Minimum observed plasma concentration at Pre-AM dose (Ctrough) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 3 time points up to Day 7 (blood) and 2 time points on Days 1 and 7 (urine) | 
| Unbound area under the concentration-time curve in one dosing interval [AUC(TAU)u] of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Area under the concentration-time curve till time of last sampling [AUC(0-T)] of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 11 (blood) and 2 (urine) time points on Day 7 | 
| Terminal elimination half life (T-Half) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Percent urinary recovery (%UR) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 3 time points up to Day 7 (urine) | 
| Apparent total body clearance (CLT/F) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Unbound apparent clearance (CLU/F) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Renal clearance (CLR) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Apparent volume of distribution (Vd/F) of Asunaprevir | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 30 time points up to Day 10 (blood) and 3 time points up to Day 7 (urine) | 
| Accumulation index (AI): Ratio of AUC(TAU) on Day 7 to AUC(TAU) on Day 1 | PK parameters will be derived from plasma concentration versus time and urinary excretion data (not applicable for subjects who are anuric) | 22 (blood) and 3 (urine) time points on Days 1 and 7 | 
| Safety and tolerability endpoints include all AEs and serious AEs, clinical laboratory tests, ECGs, vital signs and physical examination results | All recorded adverse events (AEs) will be listed and tabulated by system organ class, preferred term and renal function group. Vital signs and clinical laboratory test results will be listed and summarized by renal function group and time. Any significant physical examination findings and clinical laboratory results will be listed. Electrocardiogram (ECG) readings will be evaluated by the investigator and abnormalities, if present, will be listed | Up to Day 15 and until 30 days post discontinuation of dosing |