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

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

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

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: MK-1075


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: In each panel (A, B, C, and D), participants will receive a single dose of MK-1075 (100, 200, 400, and 800 mg, respectively) in a fasted state. Safety and viral load (VL) data from the previous panel will be assessed before dosing the subsequent panel.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |