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Trial record 57 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

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

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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C
Interventions Drug: Grazoprevir
Drug: Uprifosbuvir
Drug: Elbasvir
Drug: Ruzasvir
Drug: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir
Drug: Ribavirin
Enrollment 443
Recruitment Details This trial was conducted at 95 study sites in Asia, the European Union, and North America.
Pre-assignment Details 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)
Hide 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
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0
Lost to Follow-up             0             0             0             0             0             1             0             0             0             0             2             0             3             0             0             0             0             0
Physician Decision             0             0             0             1             0             0             0             0             0             0             0             0             1             0             0             0             0             0
Withdrawal by Subject             0             0             1             0             0             0             0             0             0             3             0             0             0             0             0             0             0             0
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
Hide 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 Number of Baseline Participants 23 24 16 14 23 23 15 16 48 31 31 35 40 15 16 26 30 16 442
Hide Baseline Analysis Population Description
The Baseline Population consists of all randomized participants who received study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants 24 participants 16 participants 14 participants 23 participants 23 participants 15 participants 16 participants 48 participants 31 participants 31 participants 35 participants 40 participants 15 participants 16 participants 26 participants 30 participants 16 participants 442 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 24 participants 16 participants 14 participants 23 participants 23 participants 15 participants 16 participants 48 participants 31 participants 31 participants 35 participants 40 participants 15 participants 16 participants 26 participants 30 participants 16 participants 442 participants
Female
10
  43.5%
13
  54.2%
7
  43.8%
5
  35.7%
14
  60.9%
9
  39.1%
9
  60.0%
8
  50.0%
21
  43.8%
16
  51.6%
16
  51.6%
14
  40.0%
11
  27.5%
3
  20.0%
4
  25.0%
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
  40.0%
8
  50.0%
27
  56.3%
15
  48.4%
15
  48.4%
21
  60.0%
29
  72.5%
12
  80.0%
12
  75.0%
17
  65.4%
16
  53.3%
7
  43.8%
250
  56.6%
1.Primary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 23 24 16 14 23 23 30 15 16 16 48 30 30 35 39 15 16 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
100.0
(85.2 to 100.0)
100.0
(85.8 to 100.0)
68.8
(41.3 to 89.0)
71.4
(41.9 to 91.6)
100.0
(85.2 to 100.0)
91.3
(72.0 to 98.9)
100.0
(88.4 to 100.0)
60.0
(32.3 to 83.7)
93.8
(69.8 to 99.8)
87.5
(61.7 to 98.4)
100.0
(92.6 to 100.0)
83.3
(65.3 to 94.4)
100.0
(88.4 to 100.0)
97.1
(85.1 to 99.9)
100.0
(91.0 to 100.0)
100.0
(78.2 to 100.0)
100.0
(79.4 to 100.0)
100.0
(86.3 to 100.0)
2.Primary Outcome
Title Percentage of Participants Experiencing an Adverse Event (AE)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 23 24 16 14 23 23 30 15 16 16 48 31 31 35 40 15 16 26
Measure Type: Number
Unit of Measure: Percentage of Participants
60.9 83.3 56.3 71.4 73.9 60.9 62.3 86.7 75.0 68.8 72.9 80.6 71.0 57.1 72.5 53.3 81.3 69.2
3.Primary Outcome
Title Percentage of Participants Discontinuing From Study Treatment Due to an AE
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 23 24 16 14 23 23 30 15 16 16 48 31 31 35 40 15 16 26
Measure Type: Number
Unit of Measure: Percentage of Participants
0 0 0 0 0 0 0 0 0 0 0 6.5 0 0 2.5 0 12.5 0
4.Secondary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24)
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 23 24 16 14 23 22 30 15 16 16 48 30 29 35 35 15 16 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
100.0
(85.2 to 100.0)
100.0
(85.8 to 100.0)
68.8
(41.3 to 89.0)
71.4
(41.9 to 91.6)
100.0
(85.2 to 100.0)
90.9
(70.8 to 98.9)
100.0
(88.4 to 100.0)
60.0
(32.3 to 83.7)
93.8
(69.8 to 99.8)
87.5
(61.7 to 98.4)
100.0
(92.6 to 100.0)
83.3
(65.3 to 94.4)
100.0
(88.1 to 100.0)
97.1
(85.1 to 99.9)
100.0
(90.1 to 100.0)
100.0
(78.2 to 100.0)
100.0
(79.4 to 100.0)
100.0
(86.3 to 100.0)
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)
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide 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 (0.00%)      1/24 (4.17%)      1/16 (6.25%)      1/14 (7.14%)      0/23 (0.00%)      0/23 (0.00%)      0/15 (0.00%)      0/16 (0.00%)      0/30 (0.00%)      1/16 (6.25%)      0/48 (0.00%)      2/31 (6.45%)      0/31 (0.00%)      1/35 (2.86%)      3/40 (7.50%)      0/15 (0.00%)      0/16 (0.00%)      2/26 (7.69%)    
Cardiac disorders                                     
Atrial fibrillation  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Tachycardia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Eye disorders                                     
Retinal artery occlusion  1  0/23 (0.00%)  0 1/24 (4.17%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Gastrointestinal disorders                                     
Duodenal ulcer haemorrhage  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Oesophagitis  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Pancreatitis  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Vomiting  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Infections and infestations                                     
Device related infection  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Pilonidal cyst  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 1/35 (2.86%)  1 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Pneumonia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Septic shock  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Musculoskeletal and connective tissue disorders                                     
Arthralgia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                     
Squamous cell carcinoma  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 1/16 (6.25%)  1 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Psychiatric disorders                                     
Depression  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Substance-induced psychotic disorder  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                                     
Dyspnoea  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (56.52%)      19/24 (79.17%)      10/16 (62.50%)      10/14 (71.43%)      15/23 (65.22%)      13/23 (56.52%)      13/15 (86.67%)      12/16 (75.00%)      18/30 (60.00%)      11/16 (68.75%)      35/48 (72.92%)      24/31 (77.42%)      19/31 (61.29%)      19/35 (54.29%)      26/40 (65.00%)      8/15 (53.33%)      13/16 (81.25%)      14/26 (53.85%)    
Blood and lymphatic system disorders                                     
Anaemia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/15 (6.67%)  1 1/16 (6.25%)  2 0/26 (0.00%)  0
Lymphadenopathy  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 3/30 (10.00%)  4 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 0/31 (0.00%)  0 1/35 (2.86%)  1 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Cardiac disorders                                     
Atrial fibrillation  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 2/26 (7.69%)  2
Palpitations  1  1/23 (4.35%)  1 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 2/23 (8.70%)  3 0/23 (0.00%)  0 1/15 (6.67%)  1 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 1/31 (3.23%)  2 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 2/16 (12.50%)  3 0/26 (0.00%)  0
Sinus bradycardia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Ear and labyrinth disorders                                     
Excessive cerumen production  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Tinnitus  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 1/31 (3.23%)  1 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Vertigo  1  0/23 (0.00%)  0 1/24 (4.17%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 2/40 (5.00%)  3 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Endocrine disorders                                     
Androgen deficiency  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Hypothyroidism  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Eye disorders                                     
Blepharospasm  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Vision blurred  1  1/23 (4.35%)  1 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 1/16 (6.25%)  1 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Gastrointestinal disorders                                     
Abdominal discomfort  1  2/23 (8.70%)  2 2/24 (8.33%)  2 0/16 (0.00%)  0 1/14 (7.14%)  1 1/23 (4.35%)  1 1/23 (4.35%)  1 1/15 (6.67%)  1 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 1/31 (3.23%)  1 1/35 (2.86%)  1 0/40 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 1/26 (3.85%)  1
Abdominal pain  1  2/23 (8.70%)  2 1/24 (4.17%)  1 2/16 (12.50%)  2 0/14 (0.00%)  0 0/23 (0.00%)  0 2/23 (8.70%)  2 1/15 (6.67%)  1 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 1/48 (2.08%)  1 1/31 (3.23%)  1 0/31 (0.00%)  0 1/35 (2.86%)  1 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 3/26 (11.54%)  3
Abdominal pain lower  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 1/15 (6.67%)  2 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 1/35 (2.86%)  1 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Abdominal pain upper  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 1/23 (4.35%)  1 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 1/31 (3.23%)  1 2/35 (5.71%)  2 0/40 (0.00%)  0 1/15 (6.67%)  1 1/16 (6.25%)  1 4/26 (15.38%)  4
Constipation  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 2/15 (13.33%)  2 0/16 (0.00%)  0 2/30 (6.67%)  2 2/16 (12.50%)  2 1/48 (2.08%)  1 2/31 (6.45%)  2 0/31 (0.00%)  0 1/35 (2.86%)  1 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Diarrhoea  1  1/23 (4.35%)  1 1/24 (4.17%)  1 1/16 (6.25%)  1 0/14 (0.00%)  0 4/23 (17.39%)  4 1/23 (4.35%)  1 0/15 (0.00%)  0 2/16 (12.50%)  2 3/30 (10.00%)  3 1/16 (6.25%)  1 5/48 (10.42%)  5 4/31 (12.90%)  4 1/31 (3.23%)  1 1/35 (2.86%)  1 1/40 (2.50%)  1 2/15 (13.33%)  2 1/16 (6.25%)  1 1/26 (3.85%)  1
Dry mouth  1  0/23 (0.00%)  0 2/24 (8.33%)  2 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/15 (0.00%)  0 1/16 (6.25%)  1 3/30 (10.00%)  3 0/16 (0.00%)  0 2/48 (4.17%)  2 1/31 (3.23%)  1 1/31 (3.23%)  1 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 2/26 (7.69%)  2
Dyspepsia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 3/15 (20.00%)  3 0/16 (0.00%)  0 0/30 (0.00%)  0 1/16 (6.25%)  2 0/48 (0.00%)  0 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Flatulence  1  1/23 (4.35%)  2 2/24 (8.33%)  2 1/16 (6.25%)  1 0/14 (0.00%)  0 2/23 (8.70%)  3 1/23 (4.35%)  1 3/15 (20.00%)  3 2/16 (12.50%)  2 0/30 (0.00%)  0 0/16 (0.00%)  0 3/48 (6.25%)  3 0/31 (0.00%)  0 2/31 (6.45%)  2 1/35 (2.86%)  1 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 2/26 (7.69%)  3
Gastrointestinal disorder  1  1/23 (4.35%)  1 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Gastrooesophageal reflux disease  1  0/23 (0.00%)  0 1/24 (4.17%)  1 1/16 (6.25%)  1 1/14 (7.14%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 2/48 (4.17%)  2 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 2/40 (5.00%)  2 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Gingival pain  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 1/16 (6.25%)  1 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Nausea  1  2/23 (8.70%)  2 3/24 (12.50%)  3 1/16 (6.25%)  1 2/14 (14.29%)  3 3/23 (13.04%)  3 0/23 (0.00%)  0 6/15 (40.00%)  8 3/16 (18.75%)  3 5/30 (16.67%)  5 2/16 (12.50%)  3 7/48 (14.58%)  7 5/31 (16.13%)  6 1/31 (3.23%)  1 1/35 (2.86%)  1 3/40 (7.50%)  3 2/15 (13.33%)  2 3/16 (18.75%)  3 4/26 (15.38%)  4
Rectal haemorrhage  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Vomiting  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 2/30 (6.67%)  2 0/16 (0.00%)  0 2/48 (4.17%)  2 1/31 (3.23%)  1 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 3/16 (18.75%)  3 2/26 (7.69%)  3
Abdominal distension  1  0/23 (0.00%)  0 1/24 (4.17%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 1/16 (6.25%)  1 1/48 (2.08%)  1 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Epigastric discomfort  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 1/16 (6.25%)  1 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 1/35 (2.86%)  1 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
General disorders                                     
Asthenia  1  0/23 (0.00%)  0 2/24 (8.33%)  2 3/16 (18.75%)  3 0/14 (0.00%)  0 2/23 (8.70%)  2 0/23 (0.00%)  0 1/15 (6.67%)  1 1/16 (6.25%)  1 0/30 (0.00%)  0 2/16 (12.50%)  2 0/48 (0.00%)  0 3/31 (9.68%)  3 1/31 (3.23%)  1 1/35 (2.86%)  1 0/40 (0.00%)  0 0/15 (0.00%)  0 3/16 (18.75%)  5 1/26 (3.85%)  2
Chills  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/30 (3.33%)  1 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 2/31 (6.45%)  2 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Crying  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Drug withdrawal syndrome  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/26 (0.00%)  0
Energy increased  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Fatigue  1  4/23 (17.39%)  5 3/24 (12.50%)  3 2/16 (12.50%)  2 2/14 (14.29%)  2 6/23 (26.09%)  6 4/23 (17.39%)  4 6/15 (40.00%)  6 6/16 (37.50%)  6 4/30 (13.33%)  4 3/16 (18.75%)  4 8/48 (16.67%)  9 4/31 (12.90%)  4 1/31 (3.23%)  1 3/35 (8.57%)  3 3/40 (7.50%)  3 1/15 (6.67%)  1 5/16 (31.25%)  5 3/26 (11.54%)  4
Feeling cold  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Influenza like illness  1  0/23 (0.00%)  0 1/24 (4.17%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 1/16 (6.25%)  1 1/48 (2.08%)  1 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 2/40 (5.00%)  2 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Oedema peripheral  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Peripheral swelling  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/26 (0.00%)  0
Pyrexia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Vessel puncture site reaction  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  3 0/26 (0.00%)  0
Hepatobiliary disorders                                     
Hepatic pain  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Infections and infestations                                     
Bronchitis  1  0/23 (0.00%)  0 1/24 (4.17%)  1 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Cellulitis  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 2/40 (5.00%)  2 1/15 (6.67%)  1 0/16 (0.00%)  0 0/26 (0.00%)  0
Cystitis  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  3 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 2/35 (5.71%)  3 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Ear infection  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Gastroenteritis  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 2/31 (6.45%)  2 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Gingivitis  1  1/23 (4.35%)  1 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 1/30 (3.33%)  1 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Influenza  1  0/23 (0.00%)  0 1/24 (4.17%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 3/48 (6.25%)  3 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Nasopharyngitis  1  0/23 (0.00%)  0 1/24 (4.17%)  2 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 3/15 (20.00%)  4 3/16 (18.75%)  3 0/30 (0.00%)  0 1/16 (6.25%)  1 1/48 (2.08%)  1 3/31 (9.68%)  3 1/31 (3.23%)  1 1/35 (2.86%)  1 3/40 (7.50%)  4 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  2
Oral herpes  1  1/23 (4.35%)  1 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 1/48 (2.08%)  2 0/31 (0.00%)  0 0/31 (0.00%)  0 1/35 (2.86%)  1 0/40 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Pneumonia  1  1/23 (4.35%)  1 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Sialoadenitis  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Sinusitis  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Tooth abscess  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/30 (3.33%)  2 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Upper respiratory tract infection  1  0/23 (0.00%)  0 2/24 (8.33%)  2 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 1/23 (4.35%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 2/30 (6.67%)  3 2/16 (12.50%)  2 1/48 (2.08%)  1 1/31 (3.23%)  1 3/31 (9.68%)  3 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 1/16 (6.25%)  2 0/26 (0.00%)  0
Urinary tract infection  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 1/31 (3.23%)  1 1/35 (2.86%)  1 1/40 (2.50%)  1 0/15 (0.00%)  0 1/16 (6.25%)  1 1/26 (3.85%)  1
Injury, poisoning and procedural complications                                     
Accidental overdose  1  0/23 (0.00%)  0 1/24 (4.17%)  1 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 1/15 (6.67%)  1 1/16 (6.25%)  1 1/30 (3.33%)  1 0/16 (0.00%)  0 2/48 (4.17%)  2 2/31 (6.45%)  2 0/31 (0.00%)  0 1/35 (2.86%)  1 0/40 (0.00%)  0 1/15 (6.67%)  1 1/16 (6.25%)  1 0/26 (0.00%)  0
Contusion  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Sunburn  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Investigations                                     
Aspartate aminotransferase increased  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Blood creatine phosphokinase increased  1  1/23 (4.35%)  1 1/24 (4.17%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  3 1/30 (3.33%)  1 1/16 (6.25%)  1 0/48 (0.00%)  0 1/31 (3.23%)  1 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Blood potassium increased  1  0/23 (0.00%)  0 1/24 (4.17%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Electrocardiogram QT prolonged  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/30 (3.33%)  1 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Haemoglobin decreased  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 2/15 (13.33%)  2 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 2/16 (12.50%)  2 0/26 (0.00%)  0
Lipase increased  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Liver function test increased  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/26 (0.00%)  0
Pulse abnormal  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Weight decreased  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 1/26 (3.85%)  1
Weight increased  1  1/23 (4.35%)  1 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/26 (0.00%)  0
Heart rate decreased  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 1/16 (6.25%)  1 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Metabolism and nutrition disorders                                     
Decreased appetite  1  0/23 (0.00%)  0 1/24 (4.17%)  1 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Diabetes mellitus inadequate control  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Increased appetite  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 2/16 (12.50%)  2 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Musculoskeletal and connective tissue disorders                                     
Arthralgia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 3/23 (13.04%)  4 1/23 (4.35%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 2/30 (6.67%)  3 3/16 (18.75%)  3 1/48 (2.08%)  2 3/31 (9.68%)  3 1/31 (3.23%)  1 1/35 (2.86%)  1 3/40 (7.50%)  3 0/15 (0.00%)  0 0/16 (0.00%)  0 2/26 (7.69%)  2
Back pain  1  2/23 (8.70%)  2 2/24 (8.33%)  2 3/16 (18.75%)  3 0/14 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/15 (0.00%)  0 2/16 (12.50%)  2 1/30 (3.33%)  1 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 1/31 (3.23%)  1 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Bursitis  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Muscle spasms  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/30 (0.00%)  0 1/16 (6.25%)  1 0/48 (0.00%)  0 1/31 (3.23%)  3 0/31 (0.00%)  0 0/35 (0.00%)  0 2/40 (5.00%)  3 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Muscular weakness  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Musculoskeletal stiffness  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Myalgia  1  0/23 (0.00%)  0 1/24 (4.17%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 3/15 (20.00%)  3 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 2/48 (4.17%)  3 1/31 (3.23%)  1 2/31 (6.45%)  3 1/35 (2.86%)  1 2/40 (5.00%)  2 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Pain in extremity  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 1/35 (2.86%)  1 0/40 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 1/26 (3.85%)  2
Musculoskeletal pain  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 2/16 (12.50%)  2 0/48 (0.00%)  0 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 1/40 (2.50%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Nervous system disorders                                     
Disturbance in attention  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/30 (0.00%)  0 0/16 (0.00%)  0 0/48 (0.00%)  0 1/31 (3.23%)  1 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/26 (0.00%)  0
Dizziness  1  1/23 (4.35%)  1 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 4/23 (17.39%)  5 0/23 (0.00%)  0 4/15 (26.67%)  5 0/16 (0.00%)  0 1/30 (3.33%)  1 0/16 (0.00%)  0 1/48 (2.08%)  4 0/31 (0.00%)  0 0/31 (0.00%)  0 1/35 (2.86%)  1 1/40 (2.50%)  1 0/15 (0.00%)  0 1/16 (6.25%)  1 0/26 (0.00%)  0
Dysgeusia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/23 (0.00%)  0 2/23 (8.70%)  2 0/15 (0.00%)  0 1/16 (6.25%)  1 1/30 (3.33%)  1 0/16 (0.00%)  0 1/48 (2.08%)  1 2/31 (6.45%)  2 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/26 (0.00%)  0
Headache  1  3/23 (13.04%)  5 7/24 (29.17%)  9 3/16 (18.75%)  4 2/14 (14.29%)  2 8/23 (34.78%)  9 3/23 (13.04%)  4 5/15 (33.33%)  5 9/16 (56.25%)  10 2/30 (6.67%)  2 3/16 (18.75%)  3 15/48 (31.25%)  25 8/31 (25.81%)  8 7/31 (22.58%)  7 5/35 (14.29%)  6 5/40 (12.50%)  11 2/15 (13.33%)  2 2/16 (12.50%)  2 4/26 (15.38%)  10
Hypoaesthesia  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/30 (0.00%)  0 0/16 (0.00%)  0 1/48 (2.08%)  1 0/31 (0.00%)  0 0/31 (0.00%)  0 0/35 (0.00%)  0 0/40 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/26 (3.85%)  1
Lethargy  1  0/23 (0.00%)  0 0/24 (0.00%)  0 0/16 (0.00%)  0 2/14 (14.29%)  2 0/23 (0.00%)  0 0/23 (0.00%)  0