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

Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01930058
• Other study ID #: 8876-003
• Secondary ID: 2013-002566-39
• Status: Completed
• Phase: Phase 1
• Start date: October 2, 2013
• Est. completion date: May 5, 2014

Study information

• Verified date: September 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: May 5, 2014
• Est. primary completion date: May 5, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• MK-8876
MK-8876 10 mg or 100 mg tablets taken q.d. by mouth.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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