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

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ClinicalTrials.gov Identifier: NCT01432535
Recruitment Status : Completed
First Posted : September 13, 2011
Results First Posted : September 25, 2013
Last Update Posted : April 7, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Renal Insufficiency
Intervention Drug: PegIFN-2b (Sylatron®)
Enrollment 25
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description 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 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. 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.
Period Title: Overall Study
Started 12 7 [1] 6
Completed 12 7 6
Not Completed 0 0 0
[1]
One participant later determined ineligible is not included in baseline/efficacy analyses.
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment Total
Hide Arm/Group Description 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 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 12 6 6 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 6 participants 6 participants 24 participants
57.33  (9.63) 64.00  (6.23) 52.67  (12.74) 57.83  (10.25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 6 participants 6 participants 24 participants
Female
1
   8.3%
0
   0.0%
1
  16.7%
2
   8.3%
Male
11
  91.7%
6
 100.0%
5
  83.3%
22
  91.7%
1.Primary Outcome
Title Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞)
Hide Description AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.
Time Frame From hour 0 (pre-dose) to 288 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with the exception of 1 moderate renal impairment participant found to be ineligible for this arm.
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 12 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pg*hr/mL
305315.22
(175840.19 to 530125.58)
435500.38
(248562.28 to 763030.40)
658413.69
(395164.74 to 10907032.58)
2.Primary Outcome
Title AUC From Time 0 to the Last Measurable Sample (AUC0-last)
Hide Description AUC0-last is a measure of the total amount of drug in the plasma from the dose to the last measurable sample.
Time Frame From hour 0 (pre-dose) up to 288 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with the exception of 1 moderate renal impairment participant found to be ineligible for this arm.
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 12 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pg*hr/mL
286946.43
(164687.09 to 499967.87)
408889.84
(232550.52 to 718944.43)
598863.88
(358269.15 to 1001029.37)
3.Primary Outcome
Title Maximum Observed Serum Concentration (Cmax)
Hide Description Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Time Frame From hour 0 (pre-dose) to 288 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with the exception of 1 moderate renal impairment participant found to be ineligible for this arm.
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 12 6 6
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
2547.85
(1115.61 to 5818.84)
3210.16
(1386.73 to 7431.24)
3551.03
(1653.85 to 7624.49)
4.Primary Outcome
Title Time to Maximum Observed Serum Concentration (Tmax)
Hide Description Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.
Time Frame From hour 0 (pre-dose) up to 288 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with the exception of 1 moderate renal impairment participant found to be ineligible for this arm.
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 12 6 6
Median (95% Confidence Interval)
Unit of Measure: hours
12.0
(9.0 to 72.0)
12.0
(12.0 to 72.0)
60.0
(24.0 to 96.3)
5.Primary Outcome
Title Apparent Terminal Half-life (T1/2)
Hide Description T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%.
Time Frame From hour 0 (pre-dose) up to 288 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with the exception of 1 moderate renal impairment participant found to be ineligible for this arm.
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 12 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours
41.9
(9.00% to 72.00%)
50.7
(12.00% to 72.00%)
58.1
(24.00% to 96.30%)
6.Primary Outcome
Title Apparent Total Body Clearance (CL/F)
Hide Description 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).
Time Frame From hour 0 (pre-dose) up to 288 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with the exception of 1 moderate renal impairment participant found to be ineligible for this arm.
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 12 6 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: mL/min
18.5
(10.42 to 32.85)
12.72
(7.10 to 22.81)
8.02
(4.71 to 13.64)
7.Primary Outcome
Title Apparent Volume of Distribution (Vd/F)
Hide Description 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.
Time Frame From hour 0 (pre-dose) up to 288 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with the exception of 1 moderate renal impairment participant found to be ineligible for this arm.
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description:
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 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.
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.
Overall Number of Participants Analyzed 12 6 6
Geometric Mean (95% Confidence Interval)
Unit of Measure: Liters
90.63
(41.76 to 196.69)
72.26
(32.88 to 158.82)
55.90
(27.30 to 114.49)
Time Frame [Not Specified]
Adverse Event Reporting Description One participant enrolled on the moderate renal impairment arm was later determined to be ineligible for this study arm; this participant is included in the safety analysis.
 
Arm/Group Title Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Hide Arm/Group Description 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 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. 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.
All-Cause Mortality
Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/12 (0.00%)      0/7 (0.00%)      1/6 (16.67%)    
Metabolism and nutrition disorders       
Hypoglycaemia  1  0/12 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Healthy Participants Participants With Moderate Renal Impairment Participants With Severe Renal Impairment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/12 (100.00%)      7/7 (100.00%)      6/6 (100.00%)    
Eye disorders       
Vision blurred  1  1/12 (8.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0
Gastrointestinal disorders       
Nausea  1  2/12 (16.67%)  2 2/7 (28.57%)  2 3/6 (50.00%)  3
Oesophagitis  1  0/12 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1
Vomiting  1  3/12 (25.00%)  3 2/7 (28.57%)  2 1/6 (16.67%)  1
Dry mouth  1  0/12 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0
General disorders       
Asthenia  1  1/12 (8.33%)  1 0/7 (0.00%)  0 1/6 (16.67%)  2
Chills  1  9/12 (75.00%)  9 5/7 (71.43%)  5 3/6 (50.00%)  3
Fatigue  1  0/12 (0.00%)  0 2/7 (28.57%)  2 0/6 (0.00%)  0
Feeling hot  1  0/12 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0
Injection site reaction  1  0/12 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0
Malaise  1  4/12 (33.33%)  4 1/7 (14.29%)  2 0/6 (0.00%)  0
Pain  1  2/12 (16.67%)  2 0/7 (0.00%)  0 1/6 (16.67%)  1
Pyrexia  1  9/12 (75.00%)  9 6/7 (85.71%)  7 4/6 (66.67%)  5
Thirst  1  0/12 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0
Infections and infestations       
Oral herpes  1  1/12 (8.33%)  1 0/7 (0.00%)  0 1/6 (16.67%)  1
Investigations       
Lymph node palpable  1  0/12 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1
Metabolism and nutrition disorders       
Decreased appetite  1  2/12 (16.67%)  2 3/7 (42.86%)  3 1/6 (16.67%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/12 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1
Back pain  1  1/12 (8.33%)  1 1/7 (14.29%)  1 0/6 (0.00%)  0
Muscle spasms  1  1/12 (8.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0
Myalgia  1  3/12 (25.00%)  3 1/7 (14.29%)  1 0/6 (0.00%)  0
Pain in extremity  1  0/12 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1
Nervous system disorders       
Dizziness  1  0/12 (0.00%)  0 2/7 (28.57%)  2 1/6 (16.67%)  1
Headache  1  8/12 (66.67%)  10 4/7 (57.14%)  4 3/6 (50.00%)  3
Hypogeusia  1  1/12 (8.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0
Psychiatric disorders       
Depression  1  0/12 (0.00%)  0 1/7 (14.29%)  1 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Epistaxis  1  0/12 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1
Nasal congestion  1  1/12 (8.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders       
Hyperhidrosis  1  1/12 (8.33%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0
Night sweats  1  1/12 (8.33%)  1 1/7 (14.29%)  1 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the Sponsor. The Investigator further agrees to provide review copies of abstracts or manuscripts for publication that report any results of the trial to the Sponsor 45 days prior to submission for publication or presentation. The Sponsor shall have the right to review and comment.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01432535     History of Changes
Other Study ID Numbers: P05655
MK-4031-350 ( Other Identifier: Merck protocol number )
First Submitted: September 9, 2011
First Posted: September 13, 2011
Results First Submitted: July 23, 2013
Results First Posted: September 25, 2013
Last Update Posted: April 7, 2017