Skip to main content
OpenTrials
Completed

NCT Number: NCT00635804

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

This study will examine the safety, tolerability and plasma pharmacokinetics of multiple doses of MK-3281 in healthy male participants in Part I, and in Hepatitis C Virus (HCV)-infected male participants in Part II. The clinical efficacy of MK-3281, as measured by viral load reduction, will also be assessed in Part II. The primary hypothesis is that twice daily administration of MK-3281 for 10 days in healthy adult male participants and for 7 days in HCV-infected male participants is sufficiently safe and well tolerated, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.

The results of this study will guide dose selection for future studies in both healthy participants and HCV-infected participants.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hepatitis C Blood-Borne Infections Communicable Diseases Digestive System Diseases Flaviviridae Infections Hepatitis Hepatitis, Viral, Human Infections Liver Diseases RNA Virus Infections Virus Diseases

Age range

18 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant is judged to be in good/stable health based on medical history, physical examination, vital signs, and laboratory safety tests performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug
  • Participant has no clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug
  • Participants with female partner(s) of childbearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
  • Participant has a clinical diagnosis of chronic HCV infection (for Part II only).

Exclusion criteria

  • Participant has a history of stroke, chronic seizures, or major neurological disorder
  • Participant has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • Participant has a history of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment
  • Participant has positive Hepatitis B surface antigen (or other evidence of active Hepatitis B infection) at the prescreening (study) visit
  • For Healthy Panel (Part I), participant has evidence of chronic Hepatitis C virus infection at the prescreening (study) visit
  • Participant has a history of documented Human Immunodeficiency Virus (HIV) infection

Treatment and study plan

MK-3281

Drug

MK-3281 capsule administered orally BID for 7 or 10 consecutive days depending on randomized dose. The PM dose of MK-3281 was not administered on Day 7 (for HCV-infected males) or Day 10 (for healthy males)

Placebo to MK-3281

Drug

Dose-matched placebo to MK-3281 capsule administered orally BID for 7 or 10 consecutive days depending on randomized dose of MK-3281 in serial panel. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).

Primary outcomes

  1. 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)

    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.

  2. 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)

    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.

Secondary outcomes

  1. 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)

    Blood samples were obtained from participants and MK-3281 AUC(0-12) was calculated at Days 1 and 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay.

  2. 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)

    Blood samples were obtained from participants and MK-3281 Cmax was calculated at Days 1 and 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay.

  3. 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)

    Blood samples were obtained from participants and MK-3281 plasma C12hr was calculated at Days 1 and 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay.

  4. 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)

    Blood samples were obtained from participants and MK-3281 Tmax was calculated at Days 1 and 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay.

  5. 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)

    Blood samples were obtained from participants and MK-3281 apparent t ½ was calculated at Day 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay. Harmonic mean t ½ and pseudo standard deviation were reported.

  6. 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)

    Blood samples were obtained from participants and the MK-3281 AUC(0-12hr) accumulation ratio was calculated for HCV+ participants and healthy participants. AUC(0-12hr) accumulation ratio calculated for healthy participants as Day 10 AUC (0-12hr) / Day 1 AUC (0-12hr). AUC(0-12hr) accumulation ratio calculated for HCV+ participants as Day 7 AUC (0-12hr) / Day 1 AUC (0-12hr).

  7. 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)

    Blood samples were obtained from participants and the MK-3281 Cmax accumulation ratio was calculated for HCV+ participants and healthy participants. Cmax accumulation ratio calculated for healthy participants as Day 10 Cmax / Day 1 Cmax. Cmax accumulation ratio calculated for HCV+ participants as Day 7 Cmax / Day 1 Cmax.

  8. 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)

    Blood samples were obtained from participants and the MK-3281 C12hr accumulation ratio was calculated for HCV+ participants and healthy participants. C12hr accumulation ratio calculated for healthy participants as Day 10 C12hr / Day 1 C12hr. C12hr accumulation ratio calculated for HCV+ participants as Day 7 C12hr / Day 1 C12hr.

  9. 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

    For evaluation of MK-3281 antiviral activity, the maximum reduction in HCV ribonucleic acid (RNA) levels over the course of the study was assessed by MK-3281 dose group in HCV+ participants and the mean maximum viral load reduction was summarized. HCV RNA levels were measured at predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours postdose on Day 1 and Day 7; pre-morning (AM) and pre-evening (PM) dose Day 2; and pre AM dose Days 3-6. For each participant, baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing, and change from baseline (difference) was calculated at each time point. The response for that participant was defined as: - (postbaseline time point - baseline) at the time point with the lowest HCV RNA level.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A 2-Part, Randomized, Double-Blind, Placebo-Controlled, Multiple-Rising Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-3281 in Healthy Male Subjects and Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-3281 in Hepatitis C Infected Male Patients

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Mar 14, 2008
Registry last updated
Sep 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.