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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)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02332707
Collaborator
(none)
443
Enrollment
18
Arms
22.5
Actual Duration (Months)

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
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 :
Jan 22, 2015
Actual Primary Completion Date :
Sep 16, 2016
Actual Study Completion Date :
Dec 6, 2016

Arms and Interventions

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 Names:
  • 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 Names:
  • MK-3682

    • Drug: Elbasvir
    One EBR 50 mg tablet (Part A), taken q.d. by mouth.
    Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • MK-3682

    • Drug: Elbasvir
    One EBR 50 mg tablet (Part A), taken q.d. by mouth.
    Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • MK-3682

    • Drug: Elbasvir
    One EBR 50 mg tablet (Part A), taken q.d. by mouth.
    Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • MK-3682

    • Drug: Elbasvir
    One EBR 50 mg tablet (Part A), taken q.d. by mouth.
    Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • MK-3682B

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) [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) [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 [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) [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02332707
    Other Study ID Numbers:
    • 3682-011
    • 2014-003304-73
    • MK-3682-011
    First Posted:
    Jan 7, 2015
    Last Update Posted:
    Jul 23, 2019
    Last Verified:
    Jul 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis C
    Hepatitis
    Ribavirin
    Grazoprevir
    Uprifosbuvir
    Ruzasvir

    Study Results

    Participant Flow

    Recruitment Details This trial was conducted at 95 study sites in Asia, the European Union, and North America.
    Pre-assignment Detail The "Number Started" row reflects the number of randomized participants who received study treatment. A total of 443 participants were randomized but 1 participant withdrew consent prior to receiving any study treatment.
    Arm/Group Title A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV B16: GT2 C GZR+UPR+RZR (16 Weeks) B6: GT1 NC GZR+UPR+RZR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks)
    Arm/Group Description In Part A, Hepatitis C virus (HCV) genotype (GT)1-infected non-cirrhotic (NC) participants took grazoprevir (GZR) 100 mg + uprifosbuvir (UPR) 300 mg + elbasvir (EBR) 50 mg once daily (q.d.) by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 fixed dose combination (FDC) tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.
    Period Title: Overall Study
    STARTED 23 24 16 14 23 23 15 16 48 31 31 35 40 15 16 26 30 16
    COMPLETED 23 24 15 13 23 22 15 16 48 28 29 35 35 15 16 26 30 16
    NOT COMPLETED 0 0 1 1 0 1 0 0 0 3 2 0 5 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV B16: GT2 C GZR+UPR+RZR (16 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) Total
    Arm/Group Description In Part A, Hepatitis C virus (HCV) genotype (GT)1-infected non-cirrhotic (NC) participants took grazoprevir (GZR) 100 mg + uprifosbuvir (UPR) 300 mg + elbasvir (EBR) 50 mg once daily (q.d.) by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. Total of all reporting groups
    Overall Participants 23 24 16 14 23 23 15 16 48 31 31 35 40 15 16 26 30 16 442
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    50.2
    (13.5)
    45.0
    (14.5)
    49.4
    (15.8)
    52.6
    (11.6)
    49.0
    (11.2)
    46.7
    (13.9)
    52.9
    (12.1)
    48.3
    (8.8)
    48.8
    (13.9)
    49.8
    (13.0)
    55.6
    (14.4)
    58.8
    (9.6)
    56.9
    (11.1)
    61.8
    (6.8)
    59.8
    (8.0)
    64.0
    (9.3)
    47.4
    (11.7)
    51.4
    (10.8)
    52.6
    (13.0)
    Sex: Female, Male (Count of Participants)
    Female
    10
    43.5%
    13
    54.2%
    7
    43.8%
    5
    35.7%
    14
    60.9%
    9
    39.1%
    9
    60%
    8
    50%
    21
    43.8%
    16
    51.6%
    16
    51.6%
    14
    40%
    11
    27.5%
    3
    20%
    4
    25%
    9
    34.6%
    14
    46.7%
    9
    56.3%
    192
    43.4%
    Male
    13
    56.5%
    11
    45.8%
    9
    56.3%
    9
    64.3%
    9
    39.1%
    14
    60.9%
    6
    40%
    8
    50%
    27
    56.3%
    15
    48.4%
    15
    48.4%
    21
    60%
    29
    72.5%
    12
    80%
    12
    75%
    17
    65.4%
    16
    53.3%
    7
    43.8%
    250
    56.6%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12)
    Description 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.
    Time Frame Up to 28 weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had SVR12 results available are included.
    Arm/Group Title A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV 16: GT2 C GZR+UPR+RZR (16 Weeks)
    Arm/Group Description In Part A, Hepatitis C virus (HCV) genotype (GT)1-infected non-cirrhotic (NC) participants took grazoprevir (GZR) 100 mg + uprifosbuvir (UPR) 300 mg + elbasvir (EBR) 50 mg once daily (q.d.) by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.
    Measure Participants 23 24 16 14 23 23 30 15 16 16 48 30 30 35 39 15 16 25
    Number (95% Confidence Interval) [Percentage of Participants]
    100.0
    434.8%
    100.0
    416.7%
    68.8
    430%
    71.4
    510%
    100.0
    434.8%
    91.3
    397%
    100.0
    666.7%
    60.0
    375%
    93.8
    195.4%
    87.5
    282.3%
    100.0
    322.6%
    83.3
    238%
    100.0
    250%
    97.1
    647.3%
    100.0
    625%
    100.0
    384.6%
    100.0
    333.3%
    100.0
    625%
    2. Primary Outcome
    Title Percentage of Participants Experiencing an Adverse Event (AE)
    Description 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 18 weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug are included.
    Arm/Group Title A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV 16: GT2 C GZR+UPR+RZR (16 Weeks)
    Arm/Group Description In Part A, Hepatitis C virus (HCV) genotype (GT)1-infected non-cirrhotic (NC) participants took grazoprevir (GZR) 100 mg + uprifosbuvir (UPR) 300 mg + elbasvir (EBR) 50 mg once daily (q.d.) by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.
    Measure Participants 23 24 16 14 23 23 30 15 16 16 48 31 31 35 40 15 16 26
    Number [Percentage of Participants]
    60.9
    264.8%
    83.3
    347.1%
    56.3
    351.9%
    71.4
    510%
    73.9
    321.3%
    60.9
    264.8%
    62.3
    415.3%
    86.7
    541.9%
    75.0
    156.3%
    68.8
    221.9%
    72.9
    235.2%
    80.6
    230.3%
    71.0
    177.5%
    57.1
    380.7%
    72.5
    453.1%
    53.3
    205%
    81.3
    271%
    69.2
    432.5%
    3. Secondary Outcome
    Title Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24)
    Description 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.
    Time Frame Up to 40 weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had SVR24 results available are included.
    Arm/Group Title A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV 16: GT2 C GZR+UPR+RZR (16 Weeks)
    Arm/Group Description In Part A, Hepatitis C virus (HCV) genotype (GT)1-infected non-cirrhotic (NC) participants took grazoprevir (GZR) 100 mg + uprifosbuvir (UPR) 300 mg + elbasvir (EBR) 50 mg once daily (q.d.) by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.
    Measure Participants 23 24 16 14 23 22 30 15 16 16 48 30 29 35 35 15 16 25
    Number (95% Confidence Interval) [Percentage of Participants]
    100.0
    434.8%
    100.0
    416.7%
    68.8
    430%
    71.4
    510%
    100.0
    434.8%
    90.9
    395.2%
    100.0
    666.7%
    60.0
    375%
    93.8
    195.4%
    87.5
    282.3%
    100.0
    322.6%
    83.3
    238%
    100.0
    250%
    97.1
    647.3%
    100.0
    625%
    100.0
    384.6%
    100.0
    333.3%
    100.0
    625%
    4. Primary Outcome
    Title Percentage of Participants Discontinuing From Study Treatment Due to an AE
    Description 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 16 weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug are included.
    Arm/Group Title A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBV B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV 16: GT2 C GZR+UPR+RZR (16 Weeks)
    Arm/Group Description In Part A, Hepatitis C virus (HCV) genotype (GT)1-infected non-cirrhotic (NC) participants took grazoprevir (GZR) 100 mg + uprifosbuvir (UPR) 300 mg + elbasvir (EBR) 50 mg once daily (q.d.) by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.
    Measure Participants 23 24 16 14 23 23 30 15 16 16 48 31 31 35 40 15 16 26
    Number [Percentage of Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    6.5
    18.6%
    0
    0%
    0
    0%
    2.5
    15.6%
    0
    0%
    12.5
    41.7%
    0
    0%

    Adverse Events

    Time Frame Up to 18 weeks (14 days after completing treatment)
    Adverse Event Reporting Description All participants who received at least 1 dose of study drug are included.
    Arm/Group Title A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBVMax 62 Characters... B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV B16: GT2 C GZR+UPR+RZR (16 Weeks)
    Arm/Group Description In Part A, Hepatitis C virus (HCV) genotype (GT)1-infected non-cirrhotic (NC) participants took grazoprevir (GZR) 100 mg + uprifosbuvir (UPR) 300 mg + elbasvir (EBR) 50 mg once daily (q.d.) by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 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. In Part B, HCV GT2-infected C participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.
    All Cause Mortality
    A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBVMax 62 Characters... B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV B16: GT2 C GZR+UPR+RZR (16 Weeks)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBVMax 62 Characters... B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV B16: GT2 C GZR+UPR+RZR (16 Weeks)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 1/24 (4.2%) 1/16 (6.3%) 1/14 (7.1%) 0/23 (0%) 0/23 (0%) 0/15 (0%) 0/16 (0%) 0/30 (0%) 1/16 (6.3%) 0/48 (0%) 2/31 (6.5%) 0/31 (0%) 1/35 (2.9%) 3/40 (7.5%) 0/15 (0%) 0/16 (0%) 2/26 (7.7%)
    Cardiac disorders
    Atrial fibrillation 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Tachycardia 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Eye disorders
    Retinal artery occlusion 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Gastrointestinal disorders
    Duodenal ulcer haemorrhage 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Oesophagitis 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Pancreatitis 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Vomiting 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Infections and infestations
    Device related infection 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Pilonidal cyst 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Pneumonia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Septic shock 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Psychiatric disorders
    Depression 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Substance-induced psychotic disorder 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Other (Not Including Serious) Adverse Events
    A1: GT1 NC GZR+UPR+EBR (8 Weeks) A2: GT1 NC GZR+UPR+RZR (8 Weeks) A3: GT2 NC GZR+UPR+EBR (8 Weeks) A4: GT2 NC GZR+UPR+RZR (8 Weeks) A5: GT1 NC GZR+UPR+EBR (8 Weeks) A6: GT1 NC GZR+UPR+RZR (8 Weeks) A7: GT2 NC GZR+UPR+EBR (8 Weeks) A8: GT2 NC GZR+UPR+RZR (8 Weeks) B6: GT1 NC GZR+UPR+RVR (8 Weeks) B8: GT2 NC GZR+UPR+RZR (8 Weeks) B9: GT1 NC GZR+UPR+RZR (12 Weeks) B10: GT2 NC GZR+UPR+RZR (8 Weeks) + RBVMax 62 Characters... B11: GT2 NC GZR+UPR+RZR (12 Weeks) B12: GT1 C GZR+UPR+RZR (8 Weeks) B13: GT1 C GZR+UPR+RZR (12 Weeks) B14: GT2 C GZR+UPR+RZR (12 Weeks) B15: GT2 C GZR+UPR+RZR (12 Weeks) + RBV B16: GT2 C GZR+UPR+RZR (16 Weeks)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/23 (56.5%) 19/24 (79.2%) 10/16 (62.5%) 10/14 (71.4%) 15/23 (65.2%) 13/23 (56.5%) 13/15 (86.7%) 12/16 (75%) 18/30 (60%) 11/16 (68.8%) 35/48 (72.9%) 24/31 (77.4%) 19/31 (61.3%) 19/35 (54.3%) 26/40 (65%) 8/15 (53.3%) 13/16 (81.3%) 14/26 (53.8%)
    Blood and lymphatic system disorders
    Anaemia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 2 0/26 (0%) 0
    Lymphadenopathy 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 3/30 (10%) 4 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 2/26 (7.7%) 2
    Palpitations 1/23 (4.3%) 1 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 2/23 (8.7%) 3 0/23 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 1/31 (3.2%) 2 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 2/16 (12.5%) 3 0/26 (0%) 0
    Sinus bradycardia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Ear and labyrinth disorders
    Excessive cerumen production 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Tinnitus 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 1/31 (3.2%) 1 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Vertigo 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 1/23 (4.3%) 1 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 2/40 (5%) 3 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Endocrine disorders
    Androgen deficiency 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Hypothyroidism 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Eye disorders
    Blepharospasm 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Vision blurred 1/23 (4.3%) 1 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 2/23 (8.7%) 2 2/24 (8.3%) 2 0/16 (0%) 0 1/14 (7.1%) 1 1/23 (4.3%) 1 1/23 (4.3%) 1 1/15 (6.7%) 1 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 1/26 (3.8%) 1
    Abdominal pain 2/23 (8.7%) 2 1/24 (4.2%) 1 2/16 (12.5%) 2 0/14 (0%) 0 0/23 (0%) 0 2/23 (8.7%) 2 1/15 (6.7%) 1 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 1/31 (3.2%) 1 0/31 (0%) 0 1/35 (2.9%) 1 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 3/26 (11.5%) 3
    Abdominal pain lower 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 1/23 (4.3%) 1 1/15 (6.7%) 2 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Abdominal pain upper 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 1/23 (4.3%) 1 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 1/31 (3.2%) 1 2/35 (5.7%) 2 0/40 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 1 4/26 (15.4%) 4
    Constipation 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 2/15 (13.3%) 2 0/16 (0%) 0 2/30 (6.7%) 2 2/16 (12.5%) 2 1/48 (2.1%) 1 2/31 (6.5%) 2 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Diarrhoea 1/23 (4.3%) 1 1/24 (4.2%) 1 1/16 (6.3%) 1 0/14 (0%) 0 4/23 (17.4%) 4 1/23 (4.3%) 1 0/15 (0%) 0 2/16 (12.5%) 2 3/30 (10%) 3 1/16 (6.3%) 1 5/48 (10.4%) 5 4/31 (12.9%) 4 1/31 (3.2%) 1 1/35 (2.9%) 1 1/40 (2.5%) 1 2/15 (13.3%) 2 1/16 (6.3%) 1 1/26 (3.8%) 1
    Dry mouth 0/23 (0%) 0 2/24 (8.3%) 2 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 1/23 (4.3%) 1 0/15 (0%) 0 1/16 (6.3%) 1 3/30 (10%) 3 0/16 (0%) 0 2/48 (4.2%) 2 1/31 (3.2%) 1 1/31 (3.2%) 1 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 2/26 (7.7%) 2
    Dyspepsia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 3/15 (20%) 3 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 2 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Flatulence 1/23 (4.3%) 2 2/24 (8.3%) 2 1/16 (6.3%) 1 0/14 (0%) 0 2/23 (8.7%) 3 1/23 (4.3%) 1 3/15 (20%) 3 2/16 (12.5%) 2 0/30 (0%) 0 0/16 (0%) 0 3/48 (6.3%) 3 0/31 (0%) 0 2/31 (6.5%) 2 1/35 (2.9%) 1 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 2/26 (7.7%) 3
    Gastrointestinal disorder 1/23 (4.3%) 1 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Gastrooesophageal reflux disease 0/23 (0%) 0 1/24 (4.2%) 1 1/16 (6.3%) 1 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 2/48 (4.2%) 2 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 2/40 (5%) 2 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Gingival pain 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 1/16 (6.3%) 1 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Nausea 2/23 (8.7%) 2 3/24 (12.5%) 3 1/16 (6.3%) 1 2/14 (14.3%) 3 3/23 (13%) 3 0/23 (0%) 0 6/15 (40%) 8 3/16 (18.8%) 3 5/30 (16.7%) 5 2/16 (12.5%) 3 7/48 (14.6%) 7 5/31 (16.1%) 6 1/31 (3.2%) 1 1/35 (2.9%) 1 3/40 (7.5%) 3 2/15 (13.3%) 2 3/16 (18.8%) 3 4/26 (15.4%) 4
    Rectal haemorrhage 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Vomiting 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 2/30 (6.7%) 2 0/16 (0%) 0 2/48 (4.2%) 2 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 3/16 (18.8%) 3 2/26 (7.7%) 3
    Abdominal distension 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 1/48 (2.1%) 1 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Epigastric discomfort 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    General disorders
    Asthenia 0/23 (0%) 0 2/24 (8.3%) 2 3/16 (18.8%) 3 0/14 (0%) 0 2/23 (8.7%) 2 0/23 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 1 0/30 (0%) 0 2/16 (12.5%) 2 0/48 (0%) 0 3/31 (9.7%) 3 1/31 (3.2%) 1 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 3/16 (18.8%) 5 1/26 (3.8%) 2
    Chills 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/30 (3.3%) 1 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 2/31 (6.5%) 2 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Crying 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Drug withdrawal syndrome 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/26 (0%) 0
    Energy increased 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Fatigue 4/23 (17.4%) 5 3/24 (12.5%) 3 2/16 (12.5%) 2 2/14 (14.3%) 2 6/23 (26.1%) 6 4/23 (17.4%) 4 6/15 (40%) 6 6/16 (37.5%) 6 4/30 (13.3%) 4 3/16 (18.8%) 4 8/48 (16.7%) 9 4/31 (12.9%) 4 1/31 (3.2%) 1 3/35 (8.6%) 3 3/40 (7.5%) 3 1/15 (6.7%) 1 5/16 (31.3%) 5 3/26 (11.5%) 4
    Feeling cold 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Influenza like illness 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 2/40 (5%) 2 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Oedema peripheral 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Peripheral swelling 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 1/23 (4.3%) 1 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/26 (0%) 0
    Pyrexia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Vessel puncture site reaction 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 3 0/26 (0%) 0
    Hepatobiliary disorders
    Hepatic pain 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Infections and infestations
    Bronchitis 0/23 (0%) 0 1/24 (4.2%) 1 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Cellulitis 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 2/40 (5%) 2 1/15 (6.7%) 1 0/16 (0%) 0 0/26 (0%) 0
    Cystitis 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 3 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 2/35 (5.7%) 3 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Ear infection 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Gastroenteritis 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 2/31 (6.5%) 2 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Gingivitis 1/23 (4.3%) 1 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 1/30 (3.3%) 1 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Influenza 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 3/48 (6.3%) 3 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Nasopharyngitis 0/23 (0%) 0 1/24 (4.2%) 2 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 3/15 (20%) 4 3/16 (18.8%) 3 0/30 (0%) 0 1/16 (6.3%) 1 1/48 (2.1%) 1 3/31 (9.7%) 3 1/31 (3.2%) 1 1/35 (2.9%) 1 3/40 (7.5%) 4 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 2
    Oral herpes 1/23 (4.3%) 1 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 2 0/31 (0%) 0 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Pneumonia 1/23 (4.3%) 1 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Sialoadenitis 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Sinusitis 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Tooth abscess 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/30 (3.3%) 2 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Upper respiratory tract infection 0/23 (0%) 0 2/24 (8.3%) 2 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 1/23 (4.3%) 1 0/15 (0%) 0 0/16 (0%) 0 2/30 (6.7%) 3 2/16 (12.5%) 2 1/48 (2.1%) 1 1/31 (3.2%) 1 3/31 (9.7%) 3 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 1/16 (6.3%) 2 0/26 (0%) 0
    Urinary tract infection 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 1/23 (4.3%) 1 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 1/31 (3.2%) 1 1/35 (2.9%) 1 1/40 (2.5%) 1 0/15 (0%) 0 1/16 (6.3%) 1 1/26 (3.8%) 1
    Injury, poisoning and procedural complications
    Accidental overdose 0/23 (0%) 0 1/24 (4.2%) 1 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 1/23 (4.3%) 1 1/15 (6.7%) 1 1/16 (6.3%) 1 1/30 (3.3%) 1 0/16 (0%) 0 2/48 (4.2%) 2 2/31 (6.5%) 2 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 1 0/26 (0%) 0
    Contusion 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Sunburn 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Investigations
    Aspartate aminotransferase increased 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Blood creatine phosphokinase increased 1/23 (4.3%) 1 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 3 1/30 (3.3%) 1 1/16 (6.3%) 1 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Blood potassium increased 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Electrocardiogram QT prolonged 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/30 (3.3%) 1 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Haemoglobin decreased 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 2/15 (13.3%) 2 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 2/16 (12.5%) 2 0/26 (0%) 0
    Lipase increased 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Liver function test increased 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/26 (0%) 0
    Pulse abnormal 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Weight decreased 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 1/26 (3.8%) 1
    Weight increased 1/23 (4.3%) 1 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/26 (0%) 0
    Heart rate decreased 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/23 (0%) 0 1/24 (4.2%) 1 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Diabetes mellitus inadequate control 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Increased appetite 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 2/16 (12.5%) 2 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 3/23 (13%) 4 1/23 (4.3%) 1 0/15 (0%) 0 0/16 (0%) 0 2/30 (6.7%) 3 3/16 (18.8%) 3 1/48 (2.1%) 2 3/31 (9.7%) 3 1/31 (3.2%) 1 1/35 (2.9%) 1 3/40 (7.5%) 3 0/15 (0%) 0 0/16 (0%) 0 2/26 (7.7%) 2
    Back pain 2/23 (8.7%) 2 2/24 (8.3%) 2 3/16 (18.8%) 3 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 0/15 (0%) 0 2/16 (12.5%) 2 1/30 (3.3%) 1 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Bursitis 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Muscle spasms 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 0/48 (0%) 0 1/31 (3.2%) 3 0/31 (0%) 0 0/35 (0%) 0 2/40 (5%) 3 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Muscular weakness 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Musculoskeletal stiffness 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Myalgia 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 3/15 (20%) 3 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 2/48 (4.2%) 3 1/31 (3.2%) 1 2/31 (6.5%) 3 1/35 (2.9%) 1 2/40 (5%) 2 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Pain in extremity 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 1/26 (3.8%) 2
    Musculoskeletal pain 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 2/16 (12.5%) 2 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Nervous system disorders
    Disturbance in attention 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/26 (0%) 0
    Dizziness 1/23 (4.3%) 1 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 4/23 (17.4%) 5 0/23 (0%) 0 4/15 (26.7%) 5 0/16 (0%) 0 1/30 (3.3%) 1 0/16 (0%) 0 1/48 (2.1%) 4 0/31 (0%) 0 0/31 (0%) 0 1/35 (2.9%) 1 1/40 (2.5%) 1 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Dysgeusia 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 2/23 (8.7%) 2 0/15 (0%) 0 1/16 (6.3%) 1 1/30 (3.3%) 1 0/16 (0%) 0 1/48 (2.1%) 1 2/31 (6.5%) 2 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Headache 3/23 (13%) 5 7/24 (29.2%) 9 3/16 (18.8%) 4 2/14 (14.3%) 2 8/23 (34.8%) 9 3/23 (13%) 4 5/15 (33.3%) 5 9/16 (56.3%) 10 2/30 (6.7%) 2 3/16 (18.8%) 3 15/48 (31.3%) 25 8/31 (25.8%) 8 7/31 (22.6%) 7 5/35 (14.3%) 6 5/40 (12.5%) 11 2/15 (13.3%) 2 2/16 (12.5%) 2 4/26 (15.4%) 10
    Hypoaesthesia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Lethargy 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 2/14 (14.3%) 2 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 2 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Paraesthesia 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 1/23 (4.3%) 1 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 1/31 (3.2%) 1 0/31 (0%) 0 1/35 (2.9%) 1 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Syncope 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Psychiatric disorders
    Affective disorder 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Anxiety 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 2/48 (4.2%) 2 1/31 (3.2%) 1 2/31 (6.5%) 2 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Depression 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 2/15 (13.3%) 3 2/16 (12.5%) 2 0/30 (0%) 0 0/16 (0%) 0 2/48 (4.2%) 2 2/31 (6.5%) 3 2/31 (6.5%) 2 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 1/26 (3.8%) 1
    Flat affect 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Initial insomnia 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Insomnia 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 2/14 (14.3%) 2 1/23 (4.3%) 1 0/23 (0%) 0 2/15 (13.3%) 3 2/16 (12.5%) 2 3/30 (10%) 3 1/16 (6.3%) 1 4/48 (8.3%) 5 4/31 (12.9%) 4 2/31 (6.5%) 2 0/35 (0%) 0 3/40 (7.5%) 3 0/15 (0%) 0 2/16 (12.5%) 2 1/26 (3.8%) 1
    Irritability 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 1/14 (7.1%) 1 1/23 (4.3%) 1 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 2/16 (12.5%) 2 1/48 (2.1%) 1 2/31 (6.5%) 2 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Libido decreased 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/30 (3.3%) 1 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Mood altered 0/23 (0%) 0 1/24 (4.2%) 1 1/16 (6.3%) 1 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Sleep disorder 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/30 (3.3%) 1 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 2 0/26 (0%) 0
    Renal and urinary disorders
    Pollakiuria 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Renal pain 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Reproductive system and breast disorders
    Erectile dysfunction 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/26 (0%) 0
    Menstruation delayed 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Ovarian cyst 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 1/23 (4.3%) 1 1/23 (4.3%) 1 1/15 (6.7%) 1 0/16 (0%) 0 1/30 (3.3%) 1 0/16 (0%) 0 3/48 (6.3%) 3 4/31 (12.9%) 5 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 2/26 (7.7%) 2
    Dyspnoea 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 1/26 (3.8%) 1
    Dyspnoea exertional 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 2/15 (13.3%) 3 0/16 (0%) 0 1/30 (3.3%) 1 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 1 1/26 (3.8%) 1
    Oropharyngeal pain 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 1/15 (6.7%) 1 2/16 (12.5%) 2 0/30 (0%) 0 0/16 (0%) 0 2/48 (4.2%) 2 1/31 (3.2%) 1 1/31 (3.2%) 1 0/35 (0%) 0 2/40 (5%) 2 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Respiratory tract congestion 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 2/31 (6.5%) 2 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Rhinorrhoea 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/23 (4.3%) 1 0/23 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Throat irritation 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 1/23 (4.3%) 1 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 1/16 (6.3%) 1 0/48 (0%) 0 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Dry skin 0/23 (0%) 0 1/24 (4.2%) 1 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 1/23 (4.3%) 1 2/15 (13.3%) 2 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 3/31 (9.7%) 3 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Erythema 1/23 (4.3%) 1 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 1/31 (3.2%) 1 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Hyperhidrosis 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 2/48 (4.2%) 2 0/31 (0%) 0 2/31 (6.5%) 2 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Macule 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Pruritus 0/23 (0%) 0 1/24 (4.2%) 1 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 2/23 (8.7%) 2 3/15 (20%) 3 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 5/31 (16.1%) 5 1/31 (3.2%) 1 0/35 (0%) 0 1/40 (2.5%) 1 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Pruritus generalised 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/30 (3.3%) 3 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 1/16 (6.3%) 1 0/26 (0%) 0
    Rash 0/23 (0%) 0 2/24 (8.3%) 3 0/16 (0%) 0 1/14 (7.1%) 1 1/23 (4.3%) 2 0/23 (0%) 0 1/15 (6.7%) 1 1/16 (6.3%) 1 0/30 (0%) 0 0/16 (0%) 0 1/48 (2.1%) 1 3/31 (9.7%) 5 0/31 (0%) 0 0/35 (0%) 0 1/40 (2.5%) 1 1/15 (6.7%) 2 0/16 (0%) 0 1/26 (3.8%) 1
    Rash papular 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 2/16 (12.5%) 2 0/26 (0%) 0
    Vitiligo 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0
    Vascular disorders
    Hot flush 0/23 (0%) 0 2/24 (8.3%) 2 0/16 (0%) 0 1/14 (7.1%) 1 2/23 (8.7%) 2 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 2/48 (4.2%) 2 0/31 (0%) 0 1/31 (3.2%) 1 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Hypertension 0/23 (0%) 0 0/24 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 2/48 (4.2%) 2 0/31 (0%) 0 1/31 (3.2%) 1 3/35 (8.6%) 3 2/40 (5%) 2 0/15 (0%) 0 0/16 (0%) 0 1/26 (3.8%) 1
    Orthostatic hypotension 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/30 (0%) 0 0/16 (0%) 0 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 1/15 (6.7%) 1 0/16 (0%) 0 0/26 (0%) 0
    Essential hypertension 0/23 (0%) 0 0/24 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 0/23 (0%) 0 0/23 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 1/30 (3.3%) 1 1/16 (6.3%) 1 0/48 (0%) 0 0/31 (0%) 0 0/31 (0%) 0 0/35 (0%) 0 0/40 (0%) 0 0/15 (0%) 0 0/16 (0%) 0 0/26 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.

    Results Point of Contact

    Name/Title Senior VIce President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02332707
    Other Study ID Numbers:
    • 3682-011
    • 2014-003304-73
    • MK-3682-011
    First Posted:
    Jan 7, 2015
    Last Update Posted:
    Jul 23, 2019
    Last Verified:
    Jul 1, 2019