Pharmacokinetic Study of BMS-914143 in Participants With Normal Renal Function and Mild, Moderate, Severe and End-stage Renal Dysfunction (PK)

An Open-label, Single Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of BMS-914143 in Subject With Normal Renal Function and Subjects With Mild, Moderate, Severe, and End-stage Renal Dysfunction

The purpose of this study is to determine the effect of renal impairment on pharmacokinetics (PK) of BMS-914143.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C Virus Infection; Chronic Hepatitis B Virus Infection
• Intervention / Treatment: Biological: BMS-914143 (Peginterferon Lambda-1a)

Detailed Description

Primary purpose: Protocol designed to evaluate the effect of renal impairment on pharmacokinetics of BMS-914143

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014-3616
      • Clinical Pharmacology Of Miami Inc.
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center For Clinical Research - Knoxville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Normal renal function or mild, moderate, severe or end-stage renal dysfunction

Exclusion Criteria:

• History of uncontrolled or unstable cardiovascular, respiratory, gastrointestinal, hepatic, endocrine, hematopoietic, psychiatric or neurological conditions within 6 months of Lambda administration
• History of chronic liver disease including cirrhosis, hepatitis B virus (HBV), hepatitis C virus (HCV), primary biliary cirrhosis, etc
• History of central nervous system or neuro-psychiatric disease. Subjects with severe depression and/or other uncontrolled psychiatric conditions should not be enrolled in this study
• History of of suicide attempt within the 5 years preceding BMS-914143 administration
• Inability to tolerate subcutaneous injections
• Donation of >400 mL of blood within 8 weeks or plasma within 4 weeks of planned dosing

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: Group 1: BMS-914143 (eGFR ≥ 80 mL/min/1.73 m2); BMS-914143 (Peginterferon Lambda-1a) single 180 µg Solution, Subcutaneous injection for subjects with normal renal function with eGFR ≥ 80 mL/min/1.73 m2	Biological: BMS-914143 (Peginterferon Lambda-1a); Other Names: Lambda
Experimental: Group 2: BMS-914143 (eGFR 60 to 79 mL/min/1.73 m2); BMS-914143 (Peginterferon Lambda-1a) single 180 µg Solution, Subcutaneous injection for subjects with mild renal dysfunction with eGFR 60 to 79 mL/min/1.73 m2	Biological: BMS-914143 (Peginterferon Lambda-1a); Other Names: Lambda
Experimental: Group 3: BMS-914143 (eGFR 30 to 59 mL/min/1.73 m2); BMS-914143 (Peginterferon Lambda-1a) single 180 µg Solution, Subcutaneous injection for subjects with moderate renal dysfunction with eGFR 30 to 59 mL/min/1.73 m2	Biological: BMS-914143 (Peginterferon Lambda-1a); Other Names: Lambda
Experimental: Group 4: BMS-914143 (eGFR 15 to 29 mL/min/1.73 m2); BMS-914143 (Peginterferon Lambda-1a) single 180 µg Solution, Subcutaneous injection for subjects with severe renal dysfunction with eGFR 15 to 29 mL/min/1.73 m2	Biological: BMS-914143 (Peginterferon Lambda-1a); Other Names: Lambda
Experimental: Group 5: BMS-914143 (eGFR < 15 mL/min/1.73 m2); BMS-914143 (Peginterferon Lambda-1a) single 180 µg Solution, Subcutaneous injection for subjects with end-stage renal dysfunction with eGFR < 15 mL/min/1.73 m2 (on hemodialysis [HD] or non-HD)	Biological: BMS-914143 (Peginterferon Lambda-1a); Other Names: Lambda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the serum concentration-time curve from time 0 extrapolated to infinity [AUC(INF)] of a single 180-μg subcutaneous (SC) dose of Lambda in subjects with normal renal function and subjects with renal dysfunction	18 time points up to Day 29
Area under the serum concentration-time curve from time 0 to the time of last quantifiable concentration [AUC(0-T)] of a single 180-μg subcutaneous (SC) dose of Lambda in subjects with normal renal function and subjects with renal dysfunction	18 time points up to Day 29
Maximum observed serum concentration (Cmax) of a single 180-μg subcutaneous (SC) dose of Lambda in subjects with normal renal function and subjects with renal dysfunction	18 time points up to Day 29
Apparent volume of distribution (Vz/F) of a single 180-μg subcutaneous (SC) dose of Lambda in subjects with normal renal function and subjects with renal dysfunction	18 time points up to Day 29
Total body clearance (CLT/F) of a single 180-μg subcutaneous (SC) dose of Lambda in subjects with normal renal function and subjects with renal dysfunction	18 time points up to Day 29

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to maximum observed serum concentration (Tmax) using serum levels of Lambda	18 time points up to Day 29
Half life (T-HALF) using serum levels of Lambda	18 time points up to Day 29
Immunogenicity assessed by serum levels of anti-Lambda antibodies	5 time points up to Day 43
Safety assessed by Vital signs measurements, electrocardiograms (ECGs), clinical laboratory tests, marked laboratory abnormalities, physical measurements, and adverse events (AEs)	Up to Day 43
Serious adverse events (SAEs) Safety assessed by Vital signs measurements, electrocardiograms (ECGs), clinical laboratory tests, marked laboratory abnormalities, physical measurements, and adverse events (AEs)	Approximately up to Day 73

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimate): October 17, 2012

Study Record Updates

• Last Update Posted (Estimate): June 5, 2013
• Last Update Submitted That Met QC Criteria: June 4, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Blood-Borne Infections; Kidney Diseases; Urologic Diseases; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Infections; Communicable Diseases; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Hepatitis B, Chronic; Hepatitis, Chronic; Renal Insufficiency; Hepatitis C, Chronic; Herpesviridae Infections
• Other Study ID Numbers: AI452-019