Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)

Study Overview
=================
Brief Summary
-----------------
This adaptive design study will evaluate the safety, pharmacokinetics, and effect on hepatitis C virus (HCV) RNA levels of multiple doses of MK-8876 in participants with HCV infection. The study will consist of 4 parts evaluating participants infected with specific hepatitis C virus genotypes and up to 10 panels allowing for additional participants to enroll in each panel as specified in the study analysis. The hypothesis evaluated in the study is that a ≥2.5 log IU/mL reduction in HCV RNA from Baseline will accompany multiple dose administration of MK-8876 in participants with HCV infection.

Official Title
-----------------
A Multiple Dose Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MK-8876 in Hepatitis C Patients

Conditions
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: MK-8876


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: is male, or female of non-childbearing potential (non-childbearing potential is defined as postmenopausal without menses for ≥1 year or after medically documented hysterectomy, oophorectomy, or tubal ligation) agrees to use a medically acceptable method of contraception through 90 days after the last dose of study drug if participant has a female partner of childbearing potential must (males should use a condom and their partner of childbearing potential must use hormonal contraception, intrauterine device, diaphragm, cervical cap, or female condom) has a body mass index (BMI) between 18 and 37 kg/m^2 has a clinical diagnosis of chronic HCV infection defined by positive serology for HCV for ≥6 months agrees to follow the smoking and other trial restrictions Exclusion Criteria: is mentally or legally institutionalized or incapacitated, has significant emotional problems at study start or has clinically significant psychiatric disorder of the last 5 years has a history of clinically significant endocrine, gastrointestinal (except HCV infection), cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases has a history of stroke, chronic seizures, or major neurological disorder has a history of cancer (except adequately treated non-melanomatous skin carcinoma, carcinoma in situ of the cervix, or other malignancies which have been successfully treated for ≥10 years has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to drugs or food has a history of clinically significant hepatic disease, Gilbert's disease, biliary tract disease, or human immunodeficiency virus has had major surgery or donated or lost >1 unit of blood within 4 weeks before the study has participated in another investigational trial within 4 weeks before the study Is unable to refrain from or anticipates the use of any medication from 2 weeks before the study and throughout the study consumes >2 glasses of alcoholic beverages per day consumes >6 servings (1 serving is  120 mg caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day is a regular user of any illicit drugs or history of drug abuse within 12 months of the study has evidence or history of chronic hepatitis not caused by HCV (except acute non-HCV-related hepatitis that resolved >6 months before the study) has previously received treatment with another HCV non-nucleoside inhibitor (previous use of other HCV investigational therapies or marketed compounds is permitted if treatment ended ≥3 months before the study) has clinical or laboratory evidence of advanced or decompensated liver disease

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A: HCV GT3 MK-8876 150 mg<br>Participants infected with HCV GT3 received 150 mg MK-8876 once daily (q.d.) by mouth for 7 days. | Drug: MK-8876<br>* MK-8876 10 mg or 100 mg tablets taken q.d. by mouth.<br>|
| Experimental: Panel B: HCV GT3 MK-8876 800 mg<br>Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days. | Drug: MK-8876<br>* MK-8876 10 mg or 100 mg tablets taken q.d. by mouth.<br>|
| Experimental: Panel E: HCV GT1a MK-8876 800 mg<br>Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days. | Drug: MK-8876<br>* MK-8876 10 mg or 100 mg tablets taken q.d. by mouth.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in HCV Viral Load | The mean change (log10) in HCV ribonucleic acid (RNA) from baseline to Day 7 was determined for each panel of participants. | Baseline and Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876 | AUC0-24hr is a measure of the mean concentration of drug in plasma after dosing to 24 hr post-dose. Plasma AUC0-24hr was calculated on Day 1 and Day 7 of MK-8876 dosing. | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7 | 
| Maximum Plasma Concentration (Cmax) of MK-8876 | Cmax is a measure of the maximum plasma concentration of drug post-dose. Plasma Cmax was determined on Day 1 and Day 7 of MK-8876 dosing. | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7 | 
| Trough Plasma Concentration (C24hr) of MK-8876 | C24hr is a measure of the plasma drug concentration 24 hours post-dose (i.e., trough concentration). Plasma C24hr was determined on Day 1 and Day 7 of MK-8876 dosing. | 24 hours post-dose on Days 1 and 7 | 
| Time to Maximum Plasma Concentration (Tmax) of MK-8876 | Tmax is a measure of time required to reach the maximum plasma drug concentration post-dose. Plasma Tmax was calculated on Day 1 and Day 7 of MK-8876 dosing. | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7 | 
| Apparent Terminal Plasma Half-life (t½) of MK-8876 | t½ is the time required for the maximum plasma drug concentration to reduce by 50% post-dose. Plasma t½ was determined on Day 7 of MK-8876 dosing. | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Day 7 |