Pharmacokinetics of Peginterferon Alfa-2b in Participants With Moderate and Severe Renal Impairment (P05655)

Phase 1

Completed

• Conditions: Renal Insufficiency
• Interventions: Drug: PegIFN-2b (Sylatron®)

• Registration Number: NCT01432535
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This study will compare the pharmacokinetics of a single dose of peginterferon alfa-2b (Sylatron®) in healthy participants to that in participants with moderate to severe impairment of kidney function.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-09
• Study First Submitted QC: 2011-09-09
• Study First Posted: 2011-09-13
• Study Start: 2011-11
• Primary Completion: 2012-08
• Study Completion: 2012-08
• Results First Submitted: 2013-07-23
• Results First Submitted QC: 2013-07-23
• Results First Posted: 2013-09-25
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-09
• Last Update Posted: 2017-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• Body Mass Index (BMI) between 19 to 40 kg/m^2, inclusive
• Moderate renal impairment and severe renal impairment and/or end-stage renal disease (ESRD) who may require hemodialysis and normal renal function
• Free of any clinically significant disease (except those related to renal disease and comorbid conditions) that requires a physician's care and would interfere with the study
• Females of reproductive potential must have used a medically accepted method of contraception for three months prior to screening and must agree to use an accepted contraceptive method during and for two months following the study
• Males must agree to use a medically accepted method of contraception during the trial and for 3 months after the study

Exclusion Criteria

• Pregnant, intend to become pregnant, or breastfeeding
• Surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
• History of any infectious disease within 4 weeks prior to study drug administration that affects ability to participate in the study
• Positive for hepatitis B surface antigen, and/or for human immunodeficiency virus (HIV) antibodies. Healthy participants positive for hepatitis C antibodies
• Previously received PegIntron®, Sylatron®, and/or Pegasys
• More than 10 cigarettes or equivalent tobacco use per day
• History of malignancy
• Hypothyroidism or hyperthyroidism
• History of depression requiring treatment with psychotherapy or medication
• History of suicidality or at risk of self-harm or harm to others
• History of autoimmune disorder requiring medical therapy
• Immune mediated renal insufficiency
• Removal of a kidney (healthy participants) or functioning renal transplant (participants with renal impairment)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Participants	PegIFN-2b (Sylatron®)	Participants with normal renal function defined as having a creatinine clearance test value of ≥80 mL/min/1.73 m\^2. Participants receive a single subcutaneous dose of PegIFN-2b, 4.5 μg/kg.
Participants with Severe Renal Impairment	PegIFN-2b (Sylatron®)	Participants with severe renal impairment defined as having a creatinine clearance test value of \<30 mL/min/1.73 m\^2 or end stage renal disease on hemodialysis. Participants receive a single subcutaneous dose of PegIFN-2b, 4.5 μg/kg.
Participants with Moderate Renal Impairment	PegIFN-2b (Sylatron®)	Participants with moderate renal impairment defined as having a creatinine clearance test value of 30-50 mL/min/1.73 m\^2. Participants receive a single subcutaneous dose of PegIFN-2b, 4.5 μg/kg.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Serum Concentration (Cmax)	From hour 0 (pre-dose) to 288 hours post-dose	Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Apparent Terminal Half-life (T1/2)	From hour 0 (pre-dose) up to 288 hours post-dose	T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%.
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞)	From hour 0 (pre-dose) to 288 hours post-dose	AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.
Time to Maximum Observed Serum Concentration (Tmax)	From hour 0 (pre-dose) up to 288 hours post-dose	Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.
Apparent Total Body Clearance (CL/F)	From hour 0 (pre-dose) up to 288 hours post-dose	CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes).
AUC From Time 0 to the Last Measurable Sample (AUC0-last)	From hour 0 (pre-dose) up to 288 hours post-dose	AUC0-last is a measure of the total amount of drug in the plasma from the dose to the last measurable sample.
Apparent Volume of Distribution (Vd/F)	From hour 0 (pre-dose) up to 288 hours post-dose	Vd/F is defined as the distribution of a medication between the plasma and the rest of the body after the dose. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug.