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

NCT00635804 | Completed Phase 1 Results

• 3 other identifiers: 3281-0022008_5072007-006245-40
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Adverse Events (AEs)

  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.

  Up to 14 days after the last dose of study drug (up to 24 days maximum)

• Number of Participants Who Discontinued Study Medication Due to AEs

  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.

  Up to 14 days after the last dose of study drug (up to 24 days maximum)

Secondary Outcomes (9)

• Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281

  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)

• Maximum Plasma Concentration (Cmax) of MK-3281

  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)

• 12-Hour Concentration of MK-3281 in Plasma (C12hr)

  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)

• Time To Reach Cmax (Tmax) of MK-3281

  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)

• Apparent Half-Life (t ½) of MK-3281

  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)

Study Arms (8)

Pt 1: MK-3281 100 mg BID (Panel A)

EXPERIMENTAL

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.

Drug: MK-3281

Pt 1: MK-3281 200 mg BID (Panel B)

EXPERIMENTAL

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.

Drug: MK-3281

Pt 1: MK-3281 400 mg BID (Panel C)

EXPERIMENTAL

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.

Drug: MK-3281

Pt 1: MK-3281 800 mg BID (Panel D)

EXPERIMENTAL

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.

Drug: MK-3281

Pt 2: MK-3281 800 mg BID (Panel E)

EXPERIMENTAL

Genotype (GT)1 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.

Drug: MK-3281

Pt 2: MK-3281 800 mg BID (Panel F)

EXPERIMENTAL

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.

Drug: MK-3281

Pt 2: MK-3281 1200 mg BID (Panel G)

EXPERIMENTAL

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.

Drug: MK-3281

Placebo

PLACEBO COMPARATOR

Participants receive dose-matched placebo to MK-3281 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).

Drug: Placebo to MK-3281

Interventions

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)

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 1200 mg BID (Panel G); Pt 2: MK-3281 800 mg BID (Panel E); Pt 2: MK-3281 800 mg BID (Panel F)

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).

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hepatitis C

Interventions

14-cyclohexyl-7-((2-(dimethylamino)ethyl)(methyl)amino)-7,8-dihydro-6H-indolo(1,2-e)(1,5)benzoxazocine-11-carboxylic acid

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2008
• First Posted: March 14, 2008
• Study Start: February 19, 2008
• Primary Completion: December 22, 2009
• Study Completion: December 22, 2009
• Last Updated: September 5, 2018
• Results First Posted: May 4, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share