Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)
- Registration Number
- NCT01930058
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 9
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Panel A: HCV GT3 MK-8876 150 mg MK-8876 Participants infected with HCV GT3 received 150 mg MK-8876 once daily (q.d.) by mouth for 7 days. Panel B: HCV GT3 MK-8876 800 mg MK-8876 Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days. Panel E: HCV GT1a MK-8876 800 mg MK-8876 Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in HCV Viral Load Baseline and Day 7 The mean change (log10) in HCV ribonucleic acid (RNA) from baseline to Day 7 was determined for each panel of participants.
- Secondary Outcome Measures
Name Time Method Maximum Plasma Concentration (Cmax) of MK-8876 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7 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.
Time to Maximum Plasma Concentration (Tmax) of MK-8876 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7 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.
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7 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.
Trough Plasma Concentration (C24hr) of MK-8876 24 hours post-dose on Days 1 and 7 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.
Apparent Terminal Plasma Half-life (t½) of MK-8876 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Day 7 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.