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

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.

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Key information

Conditions

Hepatitis C Infection Blood-Borne Infections Communicable Diseases Digestive System Diseases Flaviviridae Infections Hepatitis Hepatitis C Hepatitis, Viral, Human Infections Liver Diseases RNA Virus Infections Virus Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Ruzasvir

Drug

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.

Other names: MK-8408

Primary outcomes

Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline

Time frame: Baseline and up to Day 5

Blood was collected at baseline and on Days 1, 2, 3, 4 and 5 to determine HCV RNA levels. Least squares means (LSM) and confidence intervals (CI) were obtained from an analysis of variance (ANOVA) model with maximum log10 HCV RNA change from baseline as response and a fixed effect for treatment. The primary hypothesis was that the mean change from baseline would be a reduction of ≥3 log10. A positive change from baseline indicates a reduction from baseline in log10 HCV RNA.
Number of Participants Who Experienced One or More Adverse Events (AEs)

Time frame: Up to 61 days

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Number of Participants Who Discontinued Study Drug Due To An AE

Time frame: Up to 5 days

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-8408 in Subjects With Hepatitis C Infection

Important dates

Study start: 2014
Primary completion: 2015
Study completion: 2015
First posted: Mar 3, 2014
Registry last updated: Dec 24, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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