Safety, Pharmacokinetics, and Pharmacodynamics of Ruzasvir (MK-8408) in Participants With Hepatitis C Infection (MK-8408-003)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatitis C Infection

Treatments: Drug: Ruzasvir

Study type: Interventional

Funder types: Industry

Identifiers

NCT02076100

8408-003

MK-8408-003 (Other Identifier)

2013-005094-41 (EudraCT Number)

Details and patient eligibility

About

This is a 3-part study of Ruzasvir (MK-8408) for participants with hepatitis C infection. Successive participants will be enrolled as dose levels are evaluated to find the maximum safe and well tolerated dose of Ruzasvir. Part I will be for participants with hepatitis C virus (HCV) genotype 3 (GT3) and will run first: Part II will be for participants with HCV genotype 1a (GT1a), and Part III will be for participants with HCV genotype 2b (GT2b). Parts II and III may run concurrently. The primary study hypothesis is that a safe and tolerable dose of Ruzasvir that reduces viral load will be found to support further clinical investigation.

Enrollment: 22 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Body mass index (BMI) >=18 to<=37 kg/m^2
• In general good health, except for HCV infection
• Clinical diagnosis of chronic HCV infection exclusively GT3 (Panels A-D) or exclusively GT1a (Panels E-F), or exclusively GT2b (Panels G-H).
• Must agree to follow the smoking restrictions defined by the CRU
• Must agree to use an acceptable method of contraception during the study and for 90 days after the last dose of ruzasvir

Exclusion criteria

• Clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
• History of clinically significant hepatic disease, Gilbert's disease or biliary tract disease
• History of cancer (malignancy) with the exception of adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, or successfully-treated malignancies ≥10 years prior to screening
• History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
• Positive for hepatitis B or human immunodeficiency virus (HIV)
• Major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening
• Participated in another investigational trial within 4 weeks prior to the screening visit
• QTc interval >=470 msec (for males) or >= 480 msec (for females)
• Unable to refrain from or anticipates use of any medication (prescription and/or non-prescription) or herbal remedies beginning approximately 2 weeks prior to first study drug dose, throughout the trial until the post-trial visit
• Consumes >2 glasses of alcoholic beverages per day
• Regular user (including "recreational use") of any illicit drugs or history of drug (including alcohol) abuse within approximately 12 months
• Evidence or history of chronic hepatitis not caused by HCV
• Previous treatment with other HCV NS5A inhibitors such as MK-8742, daclatasvir, or MK-8325
• Treatment with other HCV therapies such as the HCV protease
• Evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score >=3)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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22 participants in 3 patient groups

Part I GT3 Participants

Experimental group

Description:

Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.

Treatment:

Drug: Ruzasvir

Part II GT1a Participants

Experimental group

Description:

Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.

Treatment:

Drug: Ruzasvir

Part III GT2b Participants

Experimental group

Description:

Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.

Treatment:

Drug: Ruzasvir