Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-3281 in Healthy and Hepatitis C Infected Male Participants (MK-3281-002)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00635804
First received: February 28, 2008
Last updated: March 31, 2016
Last verified: March 2016
Results First Received: February 18, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Hepatitis C
Interventions: Drug: MK-3281
Drug: Placebo to MK-3281

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Panel H, planned for GT1a/GT1b HCV-infected male participants to receive 400 mg MK-3281 orally BID for 7 consecutive days, did not enroll any participants.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
60 participants were enrolled in this study and received MK-3281 or placebo in Panels A through G.

Reporting Groups
  Description
Pt 1: MK-3281 100 mg BID (Panel A) Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.
Pt 1: MK-3281 200 mg BID (Panel B) Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.
Pt 1: MK-3281 400 mg BID (Panel C) Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.
Pt 1: MK-3281 800 mg BID (Panel D) Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.
Pt 2: MK-3281 800 mg BID (Panel E) Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.
Pt 2: MK-3281 800 mg BID (Panel F) GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.
Pt 2: MK-3281 1200 mg BID (Panel G) GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.
Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).

Participant Flow:   Overall Study
    Pt 1: MK-3281 100 mg BID (Panel A)     Pt 1: MK-3281 200 mg BID (Panel B)     Pt 1: MK-3281 400 mg BID (Panel C)     Pt 1: MK-3281 800 mg BID (Panel D)     Pt 2: MK-3281 800 mg BID (Panel E)     Pt 2: MK-3281 800 mg BID (Panel F)     Pt 2: MK-3281 1200 mg BID (Panel G)     Placebo  
STARTED     7     6     6     6     6     12     3     14  
COMPLETED     6     6     6     6     6     11     3     14  
NOT COMPLETED     1     0     0     0     0     1     0     0  
Adverse Event                 0                 0                 0                 0                 0                 1                 0                 0  
Withdrawal by Subject                 1                 0                 0                 0                 0                 0                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pt 1: MK-3281 100 mg BID (Panel A) Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.
Pt 1: MK-3281 200 mg BID (Panel B) Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.
Pt 1: MK-3281 400 mg BID (Panel C) Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.
Pt 1: MK-3281 800 mg BID (Panel D) Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.
Pt 2: MK-3281 800 mg BID (Panel E) Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.
Pt 2: MK-3281 800 mg BID (Panel F) GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.
Pt 2: MK-3281 1200 mg BID (Panel G) GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.
Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Total Total of all reporting groups

Baseline Measures
    Pt 1: MK-3281 100 mg BID (Panel A)     Pt 1: MK-3281 200 mg BID (Panel B)     Pt 1: MK-3281 400 mg BID (Panel C)     Pt 1: MK-3281 800 mg BID (Panel D)     Pt 2: MK-3281 800 mg BID (Panel E)     Pt 2: MK-3281 800 mg BID (Panel F)     Pt 2: MK-3281 1200 mg BID (Panel G)     Placebo     Total  
Number of Participants  
[units: participants]
  7     6     6     6     6     12     3     14     60  
Age  
[units: years]
Mean (Standard Deviation)
  37.1  (8.7)     36.3  (13.5)     37.0  (13.0)     34.0  (14.9)     39.2  (7.3)     47.5  (8.8)     45.0  (5.2)     39.4  (10.0)     39.9  (10.9)  
Gender  
[units: participants]
                 
Female     0     0     0     0     0     0     0     0     0  
Male     7     6     6     6     6     12     3     14     60  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Experiencing Adverse Events (AEs)   [ Time Frame: Up to 14 days after the last dose of study drug (up to 24 days maximum) ]

2.  Primary:   Number of Participants Who Discontinued Study Medication Due to AEs   [ Time Frame: Up to 14 days after the last dose of study drug (up to 24 days maximum) ]

3.  Secondary:   Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281   [ Time Frame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants) ]

4.  Secondary:   Maximum Plasma Concentration (Cmax) of MK-3281   [ Time Frame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants) ]

5.  Secondary:   12-Hour Concentration of MK-3281 in Plasma (C12hr)   [ Time Frame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants) ]

6.  Secondary:   Time To Reach Cmax (Tmax) of MK-3281   [ Time Frame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants) ]

7.  Secondary:   Apparent Half-Life (t ½) of MK-3281   [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose on Day 7 (HCV+ participants) or Day 10 (healthy participants) ]

8.  Secondary:   AUC (0-12hr) Accumulation Ratio of MK-3281   [ Time Frame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants) ]

9.  Secondary:   Cmax Accumulation Ratio of MK-3281   [ Time Frame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants) ]

10.  Secondary:   C12hr Accumulation Ratio of MK-3281   [ Time Frame: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants) ]

11.  Secondary:   Maximum HCV Viral Load Change From Baseline Over Study Following MK-3281 Dosing For 7 Days   [ Time Frame: Baseline (pre-dose Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com



Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00635804     History of Changes
Other Study ID Numbers: 3281-002
2008_507 ( Other Identifier: Merck Registration Number )
2007-006245-40 ( EudraCT Number )
Study First Received: February 28, 2008
Results First Received: February 18, 2016
Last Updated: March 31, 2016
Health Authority: Scotland: Scottish Executive Health Department