study of efficacy and safety of grazoprevir (mk-5172) + elbasvir (mk-8742) in chronic hepatitis c participants with child-pugh (cp)-b hepatic insufficiency (mk-5172-059)

Conditions: Chronic Hepatitis C

Summary: this study is being done to evaluate the efficacy and safety of the drug combination grazoprevir (gzr; mk-5172) + elbasvir (ebr; mk-8742) in participants with chronic hepatitis c virus (hcv) genotype (gt) 1, 4, or 6 infection and who have cirrhosis and child-pugh (cp) score 7-9 moderate hepatic insufficiency (cp-b). the primary hypothesis is that the percentage of hcv-infected participants with hepatic insufficiency (the cp-b population) achieving sustained viral response (svr) 12 weeks after the end of all treatment (svr12) will be greater than 60%. additionally, ten non-cirrhotic (nc) hcv-infected gt1 participants will also be given gzr + ebr at the beginning of the study; this will be done for the purpose of collecting plasma pharmacokinetic (pk) data in hcv gt1-infected participants who do not have hepatic insufficiency.

the study will be conducted sequentially in 3 parts. each participant will participate in only one part. participants will be enrolled in either part a, part b, or part c: * part a: cp-b participants will receive gzr 50 mg+ ebr 50 mg; nc participants will receive gzr 100 mg/ebr 50 mg. * part b: cp-b participants will receive gzr 100 mg + ebr 50 mg. * part c: cp-b participants will receive either gzr 50 mg or 100 mg + ebr 50 mg. study progression from part a to part b and from part b to part c will be based upon a review of safety and efficacy in parts a and b, respectively. depending upon safety and efficacy in part a, the study may progress directly from part a to part c using gzr 50 mg + ebr 50 mg, without performing part b.

Eligibility criteria:
inclusion criteria: * has documented chronic hcv gt1 infection (for arm 4 participants may have gt4 or gt6 infection) with no evidence of non-typable or mixed genotype infection * has clinical evidence of hepatic cirrhosis with a score on the child-pugh scale from 7 to 9 and not anticipated to receive a liver transplant within the next 36 weeks (for arm 1, arm 3, and arm 4) * has no evidence of cirrhosis (only for arm 2 ) * agrees to remain truly abstinent or use (or have their partner use) an acceptable method of birth control from at least 2 weeks prior to day 1 and continue until at least 14 days after last dose of study drug, or longer if dictated by local regulations exclusion criteria: * is co-infected with hepatitis b virus or human immunodeficiency virus (hiv) * has previously received direct-acting antiviral therapy for hcv * has a history of malignancy \<=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or under evaluation for other active or suspected malignancy * has cirrhosis and liver imaging results within 4 weeks prior to screening showing evidence of hepatocellular carcinoma (hcc), or is under evaluation for hcc * is currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study * has clinically-relevant drug or alcohol abuse within 12 months of screening * is pregnant or breast-feeding, or expecting to conceive or donate eggs or sperm from at least 2 weeks prior to day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations * has received organ transplants (including hematopoietic stem cell transplants) other than cornea and hair * has poor venous access * has a history of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease) * requires, or likely to require, chronic systemic administration of corticosteroids during the course of the trial * has evidence or history of chronic hepatitis not caused by hcv, including but not limited to nonalcoholic steatohepatitis (nash), drug-induced hepatitis, and autoimmune hepatitis