Clinical trial NCT01930058: Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)
Official title: A Multiple Dose Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MK-8876 in Hepatitis C Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-08-28
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Mean Change From Baseline in HCV Viral Load
timeFrame: Baseline and Day 7
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876
timeFrame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
measure: Maximum Plasma Concentration (Cmax) of MK-8876
timeFrame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
measure: Trough Plasma Concentration (C24hr) of MK-8876
timeFrame: 24 hours post-dose on Days 1 and 7
measure: Time to Maximum Plasma Concentration (Tmax) of MK-8876
timeFrame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7
measure: Apparent Terminal Plasma Half-life (t½) of MK-8876
timeFrame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Day 7
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: