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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Asunaprevir

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: June 24, 2013
• First Submitted That Met QC Criteria: June 24, 2013
• First Posted (Estimate): June 26, 2013

Study Record Updates

• Last Update Posted (Estimate): November 11, 2013
• Last Update Submitted That Met QC Criteria: November 8, 2013
• Last Verified: November 1, 2013

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: AI447-033