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

A Single Rising Dose Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MK-1075 in HCV-Infected Patients

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: MK-1075

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-1075 100 mg (Panel A); HCV-infected participants receive a single 100 mg dose of MK-1075.	Drug: MK-1075; MK-1075 supplied as 10 mg or 100 mg tablets for oral administration.
Experimental: MK-1075 200 mg (Panel B); HCV-infected participants receive a single 200 mg dose of MK-1075.	Drug: MK-1075; MK-1075 supplied as 10 mg or 100 mg tablets for oral administration.
Experimental: MK-1075 400 mg (Panel C); HCV-infected participants receive a single 400 mg dose of MK-1075.	Drug: MK-1075; MK-1075 supplied as 10 mg or 100 mg tablets for oral administration.
Experimental: MK-1075 800 mg (Panel D); HCV-infected participants receive a single 800 mg dose of MK-1075.	Drug: MK-1075; MK-1075 supplied as 10 mg or 100 mg tablets for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing an Adverse Event (AE)	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.	Up to Study Day 14
Percentage of Participants Who Discontinued Study Due to an AE	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.	Up to Study Day 14
Maximum HCV Viral Load (VL) Change From Baseline Over Time Following Single-Dose MK-1075	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.	Pre-dose (baseline), 2, 4, 8, 12, 16, 24, 32, 48, 72, and 120 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2015
• Primary Completion (Actual): August 10, 2015
• Study Completion (Actual): August 10, 2015

Study Registration Dates

• First Submitted: March 16, 2015
• First Submitted That Met QC Criteria: March 16, 2015
• First Posted (Estimate): March 19, 2015

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: 1075-002; 2015-000127-93 (EudraCT Number); MK-1075-002 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf