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Efficacy and Safety of Grazoprevir (MK-5172) and Uprifosbuvir (MK-3682) With Elbasvir (MK-8742) or Ruzasvir (MK-8408) for Chronic Hepatitis C Genotype (GT)1 and GT2 Infection (MK-3682-011)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02332707
Recruitment Status : Completed
First Posted : January 7, 2015
Results First Posted : December 21, 2017
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a randomized, three-part, open-label trial of grazoprevir (GZR; MK-5172) (100 mg) and uprifosbuvir (UPR; MK-3682) (300 mg or 450 mg), with either elbasvir (EBR; MK-8742) (50 mg) or ruzasvir (RZR; MK-8408) (60 mg), and with or without ribavirin (RBV), in treatment-naïve (TN) cirrhotic (C) or non-cirrhotic (NC) hepatitis C virus (HCV) participants with chronic HCV genotype (GT) 1 or GT2 infection. Part A will consist of 8 arms to evaluate the safety of dose combinations. In Part B, participants will take 2 UPR+GZR+RZR fixed dose combination (FDC) tablets once daily (q.d.) by mouth, with or without twice-daily (b.i.d.) RBV (200 mg capsules; weight-based dosing). Participants who relapse following completion of therapy in Part A will be offered the option of retreatment with 16 weeks of UPR+GZR+RZR with RBV in Part C (data obtained from Part C will not be used in the analysis of outcome measures).

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Grazoprevir Drug: Uprifosbuvir Drug: Elbasvir Drug: Ruzasvir Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir Drug: Ribavirin Phase 2

Detailed Description:
In Part A, study therapy will be administered as separate products, each taken q.d. by mouth. In Part B and Part C, participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg q.d. by mouth.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 443 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 With Either MK-8742 or MK-8408 in Subjects With Chronic HCV GT1 and GT2 Infection
Actual Study Start Date : January 22, 2015
Actual Primary Completion Date : September 16, 2016
Actual Study Completion Date : December 6, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: A1: GT1 NC GZR+UPR+EBR (8 weeks)
In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Elbasvir
One EBR 50 mg tablet (Part A), taken q.d. by mouth.
Other Name: MK-8742

Experimental: A2: GT1 NC GZR+UPR+RZR (8 weeks)
In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Experimental: A3: GT2 NC GZR+UPR+EBR (8 weeks)
In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Elbasvir
One EBR 50 mg tablet (Part A), taken q.d. by mouth.
Other Name: MK-8742

Experimental: A4: GT2 NC GZR+UPR+RZR (8 weeks)
In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Experimental: A5: GT1 NC GZR+UPR+EBR (8 weeks)
In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Elbasvir
One EBR 50 mg tablet (Part A), taken q.d. by mouth.
Other Name: MK-8742

Experimental: A6: GT1 NC GZR+UPR+RZR (8 weeks)
In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Experimental: B7: GT2 NC GZR+UPR+EBR (8 weeks)
In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Elbasvir
One EBR 50 mg tablet (Part A), taken q.d. by mouth.
Other Name: MK-8742

Experimental: A8: GT2 NC GZR+UPR+RZR (8 weeks)
In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Experimental: B9: GT1 NC GZR+UPR+RZR (12 weeks)
In Part B, HCV GT1-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Experimental: B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV
In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Drug: Ribavirin
RBV 200 mg capsules taken b.i.d. at a total daily dose of 800-1400 mg based on participant body weight.
Other Name: Rebetol®

Experimental: B11: GT2 NC GZR+UPR+RZR (12 weeks)
In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Experimental: B12: GT1 C GZR+UPR+RZR (8 weeks)
In Part B, HCV GT1-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Experimental: B13: GT1 C GZR+UPR+RZR (12 weeks)
In Part B, HCV GT1-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Experimental: B14: GT2 C GZR+UPR+RZR (12 weeks)
In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Experimental: B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV
In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Drug: Ribavirin
RBV 200 mg capsules taken b.i.d. at a total daily dose of 800-1400 mg based on participant body weight.
Other Name: Rebetol®

Experimental: B16: GT2 C GZR+UPR+RZR (16 weeks)
In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.
Drug: Grazoprevir
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Other Name: MK-5172

Drug: Uprifosbuvir
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682

Drug: Ruzasvir
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Other Name: MK-8408

Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Experimental: B6: GT1 NC GZR+UPR+RZR (8 weeks)
In Part B, HCV GT1-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.
Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B

Experimental: B8: GT2 NC GZR+UPR+RZR (8 weeks)
In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.
Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
Other Name: MK-3682B




Primary Outcome Measures :
  1. Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) [ Time Frame: Up to 28 weeks ]
    The percentage of participants with Hepatitis C virus (HCV) ribonucleic acid (RNA) < Lower Limit of Quantification (LLoQ) 12 weeks after completing treatment (i.e., SVR12) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL.

  2. Percentage of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to 18 weeks ]
    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.

  3. Percentage of Participants Discontinuing From Study Treatment Due to an AE [ Time Frame: Up to 16 weeks ]
    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.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24) [ Time Frame: Up to 40 weeks ]
    The percentage of participants with HCV RNA < LLoQ 24 weeks after completing treatment (i.e., SVR24) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Parts A and B:

  • Previously untreated chronic HCV GT1 or GT2 with no evidence of non-typeable or mixed genotype infection
  • Has HCV ribonucleic acid (RNA) >= 10,000 IU/mL in peripheral blood at the time of screening
  • Is NC (Part A and B)
  • Is HCV treatment naïve (defined as no prior exposure to any interferon, ribavirin, or other approved or experimental HCV-specific direct-acting antiviral agent
  • Is of non-childbearing potential or agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug and either for 14 days after the last dose of study drug if not taking RBV or for 6 months after the last dose of study drug if taking RBV (or longer if dictated by local regulations). If not abstinent from heterosexual activity, participants in Part A must use 2 acceptable forms of barrier contraception whereas participants in Part B must use 2 acceptable forms of contraception which may include oral contraceptives

Part B only:

  • Has cirrhosis of the liver
  • If coinfected with human immunodeficiency virus (HIV) is not currently on antiretroviral therapy (ART) and has no plans to initiate ART treatment while participating in this study OR has well controlled HIV on ART (the ART regimen must contain only the following antiretroviral medications: tenofovir, abacavir, lamivudine, emtricitabine, raltegravir, dolutegravir, and rilpivirine with no dose modifications or changes in drugs in the 4 weeks prior to study entry [Day 1])
  • Has at least one viable ART regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of antiretroviral drug resistance

Exclusion Criteria:

Parts A, B, and C (unless noted otherwise):

  • Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease
  • For cirrhotics (Part B only), participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >5
  • Is coinfected with hepatitis B virus
  • Is coinfected with HIV (Part A only)
  • If coinfected with HIV (Part B only), has a history of opportunistic infection in the preceding 6 months prior to screening
  • 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 is under evaluation for other active or suspected malignancy
  • Has cirrhosis and has had liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
  • Has clinically-relevant drug or alcohol abuse within 12 months of screening
  • Pregnant or breast-feeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and 90 days after the last dose of study medication, or longer if dictated by local regulations
  • Has any of the following conditions:
  • organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
  • poor venous access that precludes routine peripheral blood sampling required for this trial
  • has a history of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease)
  • current or history of any clinically significant cardiac abnormalities/dysfunction, including but not limited to: angina, congestive heart failure, myocardial infarction, pulmonary hypertension, complex congenital heart disease, cardiomyopathy, significant arrhythmia, uncontrolled hypertension, a history of use of antianginal or anti-arrhythmic agents for cardiac conditions, prolonged electrocardiogram (ECG) QTc interval (>470 ms for males or >480 ms for females by the Fridericia formula) at the screening visit, personal or family history of Torsade de pointes
  • chronic pulmonary disease, including but not limited to: clinically significant chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis
  • central nervous system (CNS) trauma requiring intubation, intracranial pressure monitoring, brain meningeal or skull surgery, or resulting in seizure, coma, permanent neurologic deficits, abnormal brain imaging, or cerebral spinal fluid (CSF) leak. Prior brain hemorrhage and/or intracranial aneurysms (whether adequately repaired or not)
  • a current, or history of, seizure disorder unless seizure was >10 years ago, a single isolated event, no history of or current use of anti-seizure medications prescribed, and a normal neurological examination is documented in trial files within 6 months of Day 1
  • a history of stroke or transient ischemic attack
  • a history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures
  • a medical/surgical conditions that may result in a need for hospitalization during the period of the study
  • any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial
  • has any condition, prestudy laboratory or ECG abnormality or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the subject
  • experiences a life-threatening serious adverse event (SAE) during the screening period
  • evidence of history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, alcoholic liver disease, and autoimmune hepatitis
  • hemoglobinopathy, including, but not limited to, thalassemia major (Parts B and C only) Parts B and C only: is a male whose female partner(s) is/are pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02332707


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02332707     History of Changes
Other Study ID Numbers: 3682-011
2014-003304-73 ( EudraCT Number )
MK-3682-011 ( Other Identifier: Merck Protocol Number )
First Posted: January 7, 2015    Key Record Dates
Results First Posted: December 21, 2017
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
MK-5172
Uprifosbuvir
Ruzasvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents