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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.
EBR was supplied as 50 mg tablets and was taken q.d. by mouth.
MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.
Percentage of Participants Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12)
SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels below the lower limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time frame: Week 24
Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 14 weeks
Number of Participants Discontinuing Study Drug Due to an AE
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 12 weeks
Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants
The MELD score provides an objective and granular assessment of liver improvement as a continuous variable. The calculation of MELD score is based on three biochemical variables (serum bilirubin, creatinine and international normalized ratio \[INR\] of prothrombin time). The MELD equation is as follows: 9.57 x ln(creatinine mg/dL) +3.78 x ln(bilirubin mg/dL) +11.2 x ln (INR) + 6.43. Scores are multiplied by 10 and rounded to the nearest whole number and range from 6 (less ill) to 40 (gravely ill). MELD scores were determined at Baseline (Day 1) and again at Week 12, Follow-up (FU) Week 12 (Week 24), and FU Week 24 (Week 36). Change from baseline in MELD score = Post-baseline MELD score - baseline MELD score.
Time frame: Baseline and Weeks 12, 24, and 36
Percentage of Participants With HCV RNA Undetectable at Weeks 2, 4, and 12
HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time frame: Week 2, 4, and 12
Percentage of Participants With HCV RNA <LLoQ at Weeks 2, 4, and 12
HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time frame: Weeks 2, 4, and 12
Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4)
SVR4 was defined as HCV RNA levels \<LLoQ 4 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time frame: Week 16
Percentage of Participants Achieving Sustained Viral Response 24 Weeks After Completing Study Therapy (SVR24)
SVR24 was defined as HCV RNA levels \<LLoQ 24 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time frame: Week 36
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