Clinical trial NCT02076100: Safety, Pharmacokinetics, and Pharmacodynamics of Ruzasvir (MK-8408) in Participants With Hepatitis C Infection (MK-8408-003)
Official title: A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-8408 in Subjects With Hepatitis C Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-03-03
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline
timeFrame: Baseline and up to Day 5
measure: Number of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to 61 days
measure: Number of Participants Who Discontinued Study Drug Due To An AE
timeFrame: Up to 5 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: