Evaluation of MK-1075 in Participants With Hepatitis C Virus (HCV) Infection (MK-1075-002)

Phase 1

Completed

• Conditions: Hepatitis C
• Interventions: Drug: MK-1075

• Registration Number: NCT02392494
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to evaluate the safety and pharmacokinetics of MK-1075, and to determine the ability of MK-1075 to reduce HCV viral load, following administration of a single dose in HCV-infected participants.

Detailed Description

Per protocol, panels may be omitted if the objectives of the study are met in preceding panels.

Study Timeline

• Study First Submitted: 2015-03-16
• Study First Submitted QC: 2015-03-16
• Study First Posted: 2015-03-19
• Study Start: 2015-04-28
• Primary Completion: 2015-08-10
• Study Completion: 2015-08-10
• Results First Submitted: 2018-05-30
• Results First Submitted QC: 2018-05-30
• Results First Posted: 2018-12-31
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-07
• Last Update Posted: 2019-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

• Male or female of non-child bearing potential
• In good health other than HCV genotype (GT) 1 infection

Exclusion Criteria

• Is mentally incapacitated or legally institutionalized
• Has a history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Has a history of cancer
• Is positive for hepatitis B surface antigen (HBsAg) or human immunodeficiency virus (HIV)
• Has participated in another investigational trial within 4 weeks (or 5 half-lives) prior to Screening
• Consumes >2 alcoholic beverages a day or uses illegal drugs
• Has evidence or history of chronic hepatitis not caused by HCV including but not limited to non-HCV viral hepatitis, non-alcoholic steatohepatitis (NASH), drug-induced hepatitis, or autoimmune hepatitis
• Has clinical or laboratory evidence of advanced or decompensated liver disease, evidence of bridging fibrosis or higher grade fibrosis (Metavir score ≥3) from prior liver biopsy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
MK-1075 400 mg (Panel C)	MK-1075	HCV-infected participants receive a single 400 mg dose of MK-1075.
MK-1075 100 mg (Panel A)	MK-1075	HCV-infected participants receive a single 100 mg dose of MK-1075.
MK-1075 200 mg (Panel B)	MK-1075	HCV-infected participants receive a single 200 mg dose of MK-1075.
MK-1075 800 mg (Panel D)	MK-1075	HCV-infected participants receive a single 800 mg dose of MK-1075.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing an Adverse Event (AE)	Up to Study Day 14	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants that experienced an AE was reported for each treatment panel.
Percentage of Participants Who Discontinued Study Due to an AE	Up to Study Day 14	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. The percentage of participants that discontinued the study due to an AE was reported for each treatment panel.
Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075	Pre-dose (baseline), 2, 4, 8, 12, 16, 24, 32, 48, 72, and 120 hours post-dose	For assessment of antiviral activity of MK-1075 at each study dose, baseline and post-dose HCV ribonucleic acid (RNA) (log10) were measured at pre-dose and 2, 4, 8, 12, 16, 24, 32, 48, 72, and 120 hours post-dose. For each participant, baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing. The estimated change from baseline in HCV RNA VL (log10) was calculated for each participant by time point after each single dose, and the maximum change (reduction) in HCV RNA was determined and reported for each treatment arm using an Analysis of Variance (ANOVA) model.