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

A Single Dose Study to Assess Pharmacokinetics of SCH 54031 in Patients With Renal Impairment (P05655)

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: PegIFN-2b (Sylatron®)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Healthy Participants; 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.	Drug: PegIFN-2b (Sylatron®); Single 4.5 μg/kg dose; Other Names: SCH 054031; MK-4031; Peginterferon alfa-2b; PegIntron®
EXPERIMENTAL: Participants with Moderate Renal Impairment; 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.	Drug: PegIFN-2b (Sylatron®); Single 4.5 μg/kg dose; Other Names: SCH 054031; MK-4031; Peginterferon alfa-2b; PegIntron®
EXPERIMENTAL: Participants with Severe Renal Impairment; 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.	Drug: PegIFN-2b (Sylatron®); Single 4.5 μg/kg dose; Other Names: SCH 054031; MK-4031; Peginterferon alfa-2b; PegIntron®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞)	AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.	From hour 0 (pre-dose) to 288 hours post-dose
AUC From Time 0 to the Last Measurable Sample (AUC0-last)	AUC0-last is a measure of the total amount of drug in the plasma from the dose to the last measurable sample.	From hour 0 (pre-dose) up to 288 hours post-dose
Maximum Observed Serum Concentration (Cmax)	Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.	From hour 0 (pre-dose) to 288 hours post-dose
Time to Maximum Observed Serum Concentration (Tmax)	Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.	From hour 0 (pre-dose) up to 288 hours post-dose
Apparent Terminal Half-life (T1/2)	T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%.	From hour 0 (pre-dose) up to 288 hours post-dose
Apparent Total Body Clearance (CL/F)	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).	From hour 0 (pre-dose) up to 288 hours post-dose
Apparent Volume of Distribution (Vd/F)	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.	From hour 0 (pre-dose) up to 288 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: September 9, 2011
• First Submitted That Met QC Criteria: September 9, 2011
• First Posted (ESTIMATE): September 13, 2011

Study Record Updates

• Last Update Posted (ACTUAL): April 7, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2b
• Other Study ID Numbers: P05655; MK-4031-350 (OTHER: Merck protocol number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php