Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Efficacy and Safety of Grazoprevir (MK-5172) and Uprifosbuvir (MK-3682) With Elbasvir (MK-8742) or Ruzasvir (MK-8408) for Chronic Hepatitis C Virus (HCV) Genotype (GT) 3, GT4, GT5, and GT6 Infection (MK-3682-012)

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: NCT02332720
Recruitment Status : Completed
First Posted : January 7, 2015
Results First Posted : July 2, 2018
Last Update Posted : July 30, 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: MK-3682B
Drug: Ribavirin (RBV)
Enrollment 413
Recruitment Details No participants were randomized to the 'B21: GT5 NC TN MK-3682B (12 weeks)' arm.
Pre-assignment Details Participants were enrolled into either Part A or Part B. Part A enrolled non-cirrhotic (NC), treatment-naïve (TN) participants with hepatitis C virus (HCV) genotype (GT) 3; Part B enrolled NC or cirrhotic (C), TN or treatment-experienced (TE) participants with HCV GT3, GT4, GT5 or GT6. Participants who relapsed in Part A were retreated in Part C.
Arm/Group Title A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) B4: GT3 NC TN MK-3682B (8 Weeks) B5: GT3 NC TN MK-3682B + RBV (8 Weeks) B6: GT3 NC TN MK-3682B (12 Weeks) B7: GT3 NC TN MK-3682B + RBV (12 Weeks) B8: GT3 NC TE MK-3682B (8 Weeks) B9: GT3 NC TE MK-3682B + RBV (8 Weeks) B10: GT3 NC TE MK-3682B (12 Weeks) B11: GT3 NC TE MK-3682B + RBV (12 Weeks) B12: GT3 NC TE MK-3682B (16 Weeks) B13: GT3 C TN MK-3682B (12 Weeks) B14: GT3 C TN MK-3682B + RBV (12 Weeks) B15: GT3 C TN MK-3682B (16 Weeks) B16: GT3 C TE MK-3682B (12 Weeks) B17: GT3 C TE MK-3682B + RBV (12 Weeks) B18: GT3 C TE MK-3682B (16 Weeks) B19: GT3 C TE MK-3682B + RBV (16 Weeks) B20: GT4 NC TN MK-3682B (8 Weeks) B21: GT5 NC TN MK-3682B (12 Weeks) B22: GT6 NC TN MK-3682B (12 Weeks)
Hide Arm/Group Description In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. In Part A, HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy received retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks. In Part B, HCV GT4-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT5-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT6-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
Period Title: Part A and Part B
Started 21 21 22 22 16 36 37 35 15 14 14 15 16 13 16 14 15 14 21 25 7 0 4
Treated 21 21 22 22 16 36 37 35 15 14 14 15 16 13 16 14 15 14 20 25 7 0 4
Completed 20 21 22 22 16 33 36 34 15 14 14 15 16 13 16 13 15 13 20 24 7 0 4
Not Completed 1 0 0 0 0 3 1 1 0 0 0 0 0 0 0 1 0 1 1 1 0 0 0
Reason Not Completed
Lost to Follow-up             1             0             0             0             0             2             1             1             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0
Adverse Event             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0
Physician Decision             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             1             0             0             0             0             0             0             0             0             0             0             0             0             0             1             0             0             0
Period Title: Part C
Started 2 [1] 1 [1] 3 [1] 2 [1] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 [2] 0 0 [2]
Completed 2 1 3 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
[1]
Part A participants who had relapsed were offered the option of retreatment in Part C.
[2]
Part B participants were not included in Part C.
Arm/Group Title A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) B4: GT3 NC TN MK-3682B (8 Weeks) B5: GT3 NC TN MK-3682B + RBV (8 Weeks) B6: GT3 NC TN MK-3682B (12 Weeks) B7: GT3 NC TN MK-3682B + RBV (12 Weeks) B8: GT3 NC TE MK-3682B (8 Weeks) B9: GT3 NC TE MK-3682B + RBV (8 Weeks) B10: GT3 NC TE MK-3682B (12 Weeks) B11: GT3 NC TE MK-3682B + RBV (12 Weeks) B12: GT3 NC TE MK-3682B (16 Weeks) B13: GT3 C TN MK-3682B (12 Weeks) B14: GT3 C TN MK-3682B + RBV (12 Weeks) B15: GT3 C TN MK-3682B (16 Weeks) B16: GT3 C TE MK-3682B (12 Weeks) B17: GT3 C TE MK-3682B + RBV (12 Weeks) B18: GT3 C TE MK-3682B (16 Weeks) B19: GT3 C TE MK-3682B + RBV (16 Weeks) B20: GT4 NC TN MK-3682B (8 Weeks) B21: GT5 NC TN MK-3682B (12 Weeks) B22: GT6 NC TN MK-3682B (12 Weeks) Total
Hide Arm/Group Description In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. In Part A, HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy received retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks In Part B, HCV GT4-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT5-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT6-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 21 21 22 22 16 36 37 35 15 14 14 15 16 13 16 14 15 14 20 25 7 0 4 412
Hide Baseline Analysis Population Description
Overall Number of Baseline Participants includes participants who received at least one dose of study drug. One 'B18: GT3 C TE MK-3682B (16 weeks)' participant did not receive any study drug.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 22 participants 22 participants 16 participants 36 participants 37 participants 35 participants 15 participants 14 participants 14 participants 15 participants 16 participants 13 participants 16 participants 14 participants 15 participants 14 participants 20 participants 25 participants 7 participants 0 participants 4 participants 412 participants
Less than 18 years 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
18 to 35 years 4 4 3 4 3 8 9 7 0 1 2 1 0 0 0 0 0 2 0 0 1 0 49
36 to 50 years 12 9 14 12 4 11 14 12 5 5 6 4 6 7 3 3 4 3 6 6 3 1 150
51 to 64 years 5 8 5 3 6 16 13 16 8 7 6 9 9 4 13 9 11 9 13 18 3 3 194
Over 64 years 0 0 0 3 3 1 1 0 2 1 0 1 1 2 0 2 0 0 1 1 0 0 19
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 22 participants 22 participants 16 participants 36 participants 37 participants 35 participants 15 participants 14 participants 14 participants 15 participants 16 participants 13 participants 16 participants 14 participants 15 participants 14 participants 20 participants 25 participants 7 participants 0 participants 4 participants 412 participants
Female
9
  42.9%
15
  71.4%
14
  63.6%
11
  50.0%
7
  43.8%
19
  52.8%
23
  62.2%
23
  65.7%
7
  46.7%
2
  14.3%
8
  57.1%
6
  40.0%
5
  31.3%
3
  23.1%
5
  31.3%
3
  21.4%
8
  53.3%
1
   7.1%
2
  10.0%
5
  20.0%
1
  14.3%
2
  50.0%
179
  43.4%
Male
12
  57.1%
6
  28.6%
8
  36.4%
11
  50.0%
9
  56.3%
17
  47.2%
14
  37.8%
12
  34.3%
8
  53.3%
12
  85.7%
6
  42.9%
9
  60.0%
11
  68.8%
10
  76.9%
11
  68.8%
11
  78.6%
7
  46.7%
13
  92.9%
18
  90.0%
20
  80.0%
6
  85.7%
2
  50.0%
233
  56.6%
1.Primary Outcome
Title Percentage of HCV GT3-infected Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12)
Hide Description SVR12 is defined as HCV ribonucleic acid (RNA) less than the lower limit of quantification (<LLOQ, 15 IU/mL) 12 weeks after the end of all study therapy. A4+B4: GT3 NC TN MK-3682B (8 weeks) arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B.
Time Frame Up to 20 weeks (Part A), up to 28 weeks (Part B)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included HCV GT3 participants who received treatment and did not have major protocol deviations that may substantially affect the results of the SVR endpoints. Therefore, only GT3 treatment arms are presented in the table below.
Arm/Group Title A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A4+B4: GT3 NC TN MK-3682B (8 Weeks) B4: GT3 NC TN MK-3682B (8 Weeks) B5: GT3 NC TN MK-3682B + RBV (8 Weeks) B6: GT3 NC TN MK-3682B (12 Weeks) B7: GT3 NC TN MK-3682B + RBV (12 Weeks) B8: GT3 NC TE MK-3682B (8 Weeks) B9: GT3 NC TE MK-3682B + RBV (8 Weeks) B10: GT3 NC TE MK-3682B (12 Weeks) B11: GT3 NC TE MK-3682B + RBV (12 Weeks) B12: GT3 NC TE MK-3682B (16 Weeks) B13: GT3 C TN MK-3682B (12 Weeks) B14: GT3 C TN MK-3682B + RBV (12 Weeks) B15: GT3 C TN MK-3682B (16 Weeks) B16: GT3 C TE MK-3682B (12 Weeks) B17: GT3 C TE MK-3682B + RBV (12 Weeks) B18: GT3 C TE MK-3682B (16 Weeks) B19: GT3 C TE MK-3682B + RBV (16 Weeks)
Hide Arm/Group Description:
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks.
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks.
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks.
In Part A, HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks.
HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks during Part A or 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks during Part B.
HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks during Part B
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks.
Overall Number of Participants Analyzed 21 21 22 22 38 16 35 36 35 15 14 14 15 16 13 16 13 15 14 20 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
90.5
(69.6 to 98.8)
95.2
(76.2 to 99.9)
86.4
(65.1 to 97.1)
90.9
(70.8 to 98.9)
92.1
(78.6 to 98.3)
93.8
(69.8 to 99.8)
100.0
(90.0 to 100.0)
97.2
(85.5 to 99.9)
100.0
(90.0 to 100.0)
100.0
(78.2 to 100.0)
92.9
(66.1 to 99.8)
100.0
(76.8 to 100.0)
93.3
(68.1 to 99.8)
93.8
(69.8 to 99.8)
92.3
(64.0 to 99.8)
100.0
(79.4 to 100.0)
100.0
(75.3 to 100.0)
100.0
(78.2 to 100.0)
100.0
(76.8 to 100.0)
100.0
(83.2 to 100.0)
96.0
(79.6 to 99.9)
2.Primary Outcome
Title Number of Participants Experiencing an Adverse Event (AE)
Hide Description An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Part C in the table below combines all (eight) participants from the four distinct arms of Part A who relapsed and were subsequently treated with MK-3682B + RBV for 16 weeks.
Time Frame Up to 40 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug, categorized according to the treatment actually received. A4+B4 arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B. Part C arm includes participants who relapsed following the completion of Part A therapy and received treatment during Part C.
Arm/Group Title A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A4+ B4: GT3 NC TN MK-3682B (8 Weeks) B4: GT3 NC TN MK-3682B (8 Weeks) B5: GT3 NC TN MK-3682B + RBV (8 Weeks) B6: GT3 NC TN MK-3682B (12 Weeks) B7: GT3 NC TN MK-3682B + RBV (12 Weeks) B8: GT3 NC TE MK-3682B (8 Weeks) B9: GT3 NC TE MK-3682B + RBV (8 Weeks) B10: GT3 NC TE MK-3682B (12 Weeks) B11: GT3 NC TE MK-3682B + RBV (12 Weeks) B12: GT3 NC TE MK-3682B (16 Weeks) B13: GT3 C TN MK-3682B (12 Weeks) B14: GT3 C TN MK-3682B + RBV (12 Weeks) B15: GT3 C TN MK-3682B (16 Weeks) B16: GT3 C TE MK-3682B (12 Weeks) B17: GT3 C TE MK-3682B + RBV (12 Weeks) B18: GT3 C TE MK-3682B (16 Weeks) B19: GT3 C TE MK-3682B + RBV (16 Weeks) B20: GT4 NC TN MK-3682B (8 Weeks) B22: GT6 NC TN MK-3682B (12 Weeks) Part C: GT3 NC TN: MK-3682B + RBV (16 Weeks)
Hide Arm/Group Description:
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy received retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks during Part A or 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks during Part B.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks.
In Part B, HCV GT4-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.
In Part B, HCV GT6-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
Overall Number of Participants Analyzed 21 21 22 22 38 16 36 37 35 15 14 14 15 16 13 16 14 15 14 20 25 7 4 8
Measure Type: Count of Participants
Unit of Measure: Participants
18
  85.7%
14
  66.7%
16
  72.7%
17
  77.3%
26
  68.4%
9
  56.3%
30
  83.3%
25
  67.6%
33
  94.3%
12
  80.0%
12
  85.7%
9
  64.3%
13
  86.7%
13
  81.3%
9
  69.2%
14
  87.5%
12
  85.7%
12
  80.0%
12
  85.7%
16
  80.0%
21
  84.0%
3
  42.9%
3
  75.0%
7
  87.5%
3.Primary Outcome
Title Number of Participants Who Had Study Drug Discontinued Due to an AE
Hide Description An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Part C in the table below combines all (eight) participants from the four distinct arms of Part A who relapsed and were subsequently treated with MK-3682B + RBV for 16 weeks.
Time Frame Up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug, categorized according to the treatment actually received. A4+B4 arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B. Part C arm includes participants who relapsed following the completion of Part A therapy and received treatment during Part C.
Arm/Group Title A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A4+ B4: GT3 NC TN MK-3682B (8 Weeks) B4: GT3 NC TN MK-3682B (8 Weeks) B5: GT3 NC TN MK-3682B + RBV (8 Weeks) B6: GT3 NC TN MK-3682B (12 Weeks) B7: GT3 NC TN MK-3682B + RBV (12 Weeks) B8: GT3 NC TE MK-3682B (8 Weeks) B9: GT3 NC TE MK-3682B + RBV (8 Weeks) B10: GT3 NC TE MK-3682B (12 Weeks) B11: GT3 NC TE MK-3682B + RBV (12 Weeks) B12: GT3 NC TE MK-3682B (16 Weeks) B13: GT3 C TN MK-3682B (12 Weeks) B14: GT3 C TN MK-3682B + RBV (12 Weeks) B15: GT3 C TN MK-3682B (16 Weeks) B16: GT3 C TE MK-3682B (12 Weeks) B17: GT3 C TE MK-3682B + RBV (12 Weeks) B18: GT3 C TE MK-3682B (16 Weeks) B19: GT3 C TE MK-3682B + RBV (16 Weeks) B20: GT4 NC TN MK-3682B (8 Weeks) B22: GT6 NC TN MK-3682B (12 Weeks) Part C: GT3 NC TN: MK-3682B + RBV (16 Weeks)
Hide Arm/Group Description:
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy received retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks during Part A or 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks during Part B.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks.
In Part B, HCV GT4-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.
In Part B, HCV GT6-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
Overall Number of Participants Analyzed 21 21 22 22 38 16 36 37 35 15 14 14 15 16 13 16 14 15 14 20 25 7 4 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.9%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.3%
1
   7.1%
0
   0.0%
0
   0.0%
1
   5.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4.Secondary Outcome
Title Percentage of GT3-infected Participants Achieving SVR at Follow-up Week 24 (SVR24)
Hide Description SVR24 is defined as HCV RNA <LLOQ of 15 IU/mL 24 weeks after the end of all study therapy. A4+B4: GT3 NC TN MK-3682B (8 weeks) arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B.
Time Frame Up to 40 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included HCV GT3 participants who received treatment and did not have major protocol deviations that may substantially affect the results of the SVR endpoints. Therefore, only GT3 treatment arms are presented in the table below.
Arm/Group Title A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 Weeks) A4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 Weeks) A4+B4: GT3 NC TN MK-3682B (8 Weeks) B4: GT3 NC TN MK-3682B (8 Weeks) B5: GT3 NC TN MK-3682B + RBV (8 Weeks) B6: GT3 NC TN MK-3682B (12 Weeks) B7: GT3 NC TN MK-3682B + RBV (12 Weeks) B8: GT3 NC TE MK-3682B (8 Weeks) B9: GT3 NC TE MK-3682B + RBV (8 Weeks) B10: GT3 NC TE MK-3682B (12 Weeks) B11: GT3 NC TE MK-3682B + RBV (12 Weeks) B12: GT3 NC TE MK-3682B (16 Weeks) B13: GT3 C TN MK-3682B (12 Weeks) B14: GT3 C TN MK-3682B + RBV (12 Weeks) B15: GT3 C TN MK-3682B (16 Weeks) B16: GT3 C TE MK-3682B (12 Weeks) B17: GT3 C TE MK-3682B + RBV (12 Weeks) B18: GT3 C TE MK-3682B (16 Weeks) B19: GT3 C TE MK-3682B + RBV (16 Weeks)
Hide Arm/Group Description:
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part A, HCV GT3-infected NC TN participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy received retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks.
In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks.
Overall Number of Participants Analyzed 20 21 22 22 38 16 33 36 34 15 14 14 15 16 13 16 13 15 13 20 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
90.0
(68.3 to 98.8)
95.2
(76.2 to 99.9)
86.4
(65.1 to 97.1)
90.9
(70.8 to 98.9)
92.1
(78.6 to 98.3)
93.8
(69.8 to 99.8)
100.0
(89.4 to 100.0)
97.2
(85.5 to 99.9)
100.0
(89.7 to 100.0)
100.0
(78.2 to 100.0)
92.9
(66.1 to 99.8)
100.0
(76.8 to 100.0)
93.3
(68.1 to 99.8)
93.8
(69.8 to 99.8)
92.3
(64.0 to 99.8)
100.0
(79.4 to 100.0)
100.0
(75.3 to 100.0)
100.0
(78.2 to 100.0)
100.0
(75.3 to 100.0)
100.0
(83.2 to 100.0)
96.0
(79.6 to 99.9)
Time Frame Up to 80 weeks (Parts A and B: 8 weeks or up to 16 weeks of treatment, respectively, plus 24-week follow-up; Part C: up to 16 weeks of retreatment plus 24-week follow-up)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title A1: GT3 NC TN EBR+GZR+UPR300 (8 Wks) A1+C: GT3 NC TN EBR+GZR+UPR300 (8 Wks); MK-3682B+RBV (16 Wks) A2: GT3 NC TN GZR+RZR+UPR300 (8 Wks) A2+C: GT3 NC TN GZR+RZR+UPR300 (8 Wks); MK-3682B+RBV (16 Wks) A3: GT3 NC TN EBR+GZR+UPR450 (8 Wks) A3+C: GT3 NC TN EBR+GZR+UPR450 (8 Wks); MK-3682B+RBV (16 Wks) A4: GT3 NC TN GZR+RZR+UPR450 (8 Wks) A4+C: GT3 NC TN GZR+RZR+UPR450 (8 Wks); MK-3682B+RBV (16 Wks) B4: GT3 NC TN MK-3682B (8 Wks) B5: GT3 NC TN MK-3682B + RBV (8 Wks) B6: GT3 NC TN MK-3682B (12 Wks) B7: GT3 NC TN MK-3682B + RBV (12 Wks) B8: GT3 NC TE MK-3682B (8 Wks) B9: GT3 NC TE MK-3682B + RBV (8 Wks) B10: GT3 NC TE MK-3682B (12 Wks) B11: GT3 NC TE MK-3682B + RBV (12 Wks) B12: GT3 NC TE MK-3682B (16 Wks) B13: GT3 C TN MK-3682B (12 Wks) B14: GT3 C TN MK-3682B + RBV (12 Wks) B15: GT3 C TN MK-3682B (16 Wks) B16: GT3 C TE MK-3682B (12 Wks) B17: GT3 C TE MK-3682B + RBV (12 Wks) B18: GT3 C TE MK-3682B (16 Wks) B19: GT3 C TE MK-3682B + RBV (16 Wks) B20: GT4 NC TN MK-3682B (8 Wks) B22: GT6 NC TN MK-3682B (12 Wks)
Hide Arm/Group Description In Part A, participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. In Part A, participants received grazoprevir (100 mg) + uprifosbuvir 300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. After relapsing, participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks in Part C. In Part A, participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. In Part A, participants received grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. After relapsing, participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks in Part C. In Part A, participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. In Part A, participants received grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. After relapsing, participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks in Part C. In Part A, participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks. In Part A, participants received grazoprevir 100 mg + uprifosbuvir 450 mg + ruzasvir 60 mg q.d. by mouth for 8 weeks. After relapsing, participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks in Part C. In Part B, participants received 2 MK- 3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B , participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected NC TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected C TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. In Part B, HCV GT3-infected C TE participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks. In Part B, HCV GT4-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT6-infected NC TN participants received 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks.
All-Cause Mortality
A1: GT3 NC TN EBR+GZR+UPR300 (8 Wks) A1+C: GT3 NC TN EBR+GZR+UPR300 (8 Wks); MK-3682B+RBV (16 Wks) A2: GT3 NC TN GZR+RZR+UPR300 (8 Wks) A2+C: GT3 NC TN GZR+RZR+UPR300 (8 Wks); MK-3682B+RBV (16 Wks) A3: GT3 NC TN EBR+GZR+UPR450 (8 Wks) A3+C: GT3 NC TN EBR+GZR+UPR450 (8 Wks); MK-3682B+RBV (16 Wks) A4: GT3 NC TN GZR+RZR+UPR450 (8 Wks) A4+C: GT3 NC TN GZR+RZR+UPR450 (8 Wks); MK-3682B+RBV (16 Wks) B4: GT3 NC TN MK-3682B (8 Wks) B5: GT3 NC TN MK-3682B + RBV (8 Wks) B6: GT3 NC TN MK-3682B (12 Wks) B7: GT3 NC TN MK-3682B + RBV (12 Wks) B8: GT3 NC TE MK-3682B (8 Wks) B9: GT3 NC TE MK-3682B + RBV (8 Wks) B10: GT3 NC TE MK-3682B (12 Wks) B11: GT3 NC TE MK-3682B + RBV (12 Wks) B12: GT3 NC TE MK-3682B (16 Wks) B13: GT3 C TN MK-3682B (12 Wks) B14: GT3 C TN MK-3682B + RBV (12 Wks) B15: GT3 C TN MK-3682B (16 Wks) B16: GT3 C TE MK-3682B (12 Wks) B17: GT3 C TE MK-3682B + RBV (12 Wks) B18: GT3 C TE MK-3682B (16 Wks) B19: GT3 C TE MK-3682B + RBV (16 Wks) B20: GT4 NC TN MK-3682B (8 Wks) B22: GT6 NC TN MK-3682B (12 Wks)
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 (%) 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   0/19 (0.00%)      0/2 (0.00%)      0/20 (0.00%)      0/1 (0.00%)      0/19 (0.00%)      0/3 (0.00%)      0/20 (0.00%)      0/2 (0.00%)      0/16 (0.00%)      0/36 (0.00%)      0/37 (0.00%)      0/35 (0.00%)      0/15 (0.00%)      0/14 (0.00%)      0/14 (0.00%)      0/15 (0.00%)      0/16 (0.00%)      0/13 (0.00%)      0/16 (0.00%)      0/14 (0.00%)      0/15 (0.00%)      0/14 (0.00%)      0/20 (0.00%)      0/25 (0.00%)      0/7 (0.00%)      0/4 (0.00%)    
Hide Serious Adverse Events
A1: GT3 NC TN EBR+GZR+UPR300 (8 Wks) A1+C: GT3 NC TN EBR+GZR+UPR300 (8 Wks); MK-3682B+RBV (16 Wks) A2: GT3 NC TN GZR+RZR+UPR300 (8 Wks) A2+C: GT3 NC TN GZR+RZR+UPR300 (8 Wks); MK-3682B+RBV (16 Wks) A3: GT3 NC TN EBR+GZR+UPR450 (8 Wks) A3+C: GT3 NC TN EBR+GZR+UPR450 (8 Wks); MK-3682B+RBV (16 Wks) A4: GT3 NC TN GZR+RZR+UPR450 (8 Wks) A4+C: GT3 NC TN GZR+RZR+UPR450 (8 Wks); MK-3682B+RBV (16 Wks) B4: GT3 NC TN MK-3682B (8 Wks) B5: GT3 NC TN MK-3682B + RBV (8 Wks) B6: GT3 NC TN MK-3682B (12 Wks) B7: GT3 NC TN MK-3682B + RBV (12 Wks) B8: GT3 NC TE MK-3682B (8 Wks) B9: GT3 NC TE MK-3682B + RBV (8 Wks) B10: GT3 NC TE MK-3682B (12 Wks) B11: GT3 NC TE MK-3682B + RBV (12 Wks) B12: GT3 NC TE MK-3682B (16 Wks) B13: GT3 C TN MK-3682B (12 Wks) B14: GT3 C TN MK-3682B + RBV (12 Wks) B15: GT3 C TN MK-3682B (16 Wks) B16: GT3 C TE MK-3682B (12 Wks) B17: GT3 C TE MK-3682B + RBV (12 Wks) B18: GT3 C TE MK-3682B (16 Wks) B19: GT3 C TE MK-3682B + RBV (16 Wks) B20: GT4 NC TN MK-3682B (8 Wks) B22: GT6 NC TN MK-3682B (12 Wks)
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 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   1/19 (5.26%)      0/2 (0.00%)      0/20 (0.00%)      0/1 (0.00%)      1/19 (5.26%)      0/3 (0.00%)      0/20 (0.00%)      1/2 (50.00%)      0/16 (0.00%)      1/36 (2.78%)      0/37 (0.00%)      1/35 (2.86%)      0/15 (0.00%)      0/14 (0.00%)      0/14 (0.00%)      0/15 (0.00%)      1/16 (6.25%)      1/13 (7.69%)      0/16 (0.00%)      2/14 (14.29%)      2/15 (13.33%)      2/14 (14.29%)      2/20 (10.00%)      1/25 (4.00%)      0/7 (0.00%)      0/4 (0.00%)    
Cardiac disorders                                                     
Coronary artery disease  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 1/20 (5.00%)  1 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Eye disorders                                                     
Keratitis  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 1/19 (5.26%)  1 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Gastrointestinal disorders                                                     
Abdominal pain lower  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 1/25 (4.00%)  1 0/7 (0.00%)  0 0/4 (0.00%)  0
Hepatobiliary disorders                                                     
Biliary colic  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 1/20 (5.00%)  1 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations                                                     
Pharyngeal abscess  1  1/19 (5.26%)  1 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Injury, poisoning and procedural complications                                                     
Tendon rupture  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Investigations                                                     
Blood sodium decreased  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 1/2 (50.00%)  1 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                                     
Hepatocellular carcinoma  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/13 (7.69%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Inflammatory pseudotumour  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Lip and/or oral cavity cancer stage 0  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Nervous system disorders                                                     
Cerebral haemorrhage  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Migraine  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 1/35 (2.86%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Psychiatric disorders                                                     
Alcohol abuse  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Anxiety  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 1/2 (50.00%)  1 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Mental status changes  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                                                     
Chronic obstructive pulmonary disease  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
A1: GT3 NC TN EBR+GZR+UPR300 (8 Wks) A1+C: GT3 NC TN EBR+GZR+UPR300 (8 Wks); MK-3682B+RBV (16 Wks) A2: GT3 NC TN GZR+RZR+UPR300 (8 Wks) A2+C: GT3 NC TN GZR+RZR+UPR300 (8 Wks); MK-3682B+RBV (16 Wks) A3: GT3 NC TN EBR+GZR+UPR450 (8 Wks) A3+C: GT3 NC TN EBR+GZR+UPR450 (8 Wks); MK-3682B+RBV (16 Wks) A4: GT3 NC TN GZR+RZR+UPR450 (8 Wks) A4+C: GT3 NC TN GZR+RZR+UPR450 (8 Wks); MK-3682B+RBV (16 Wks) B4: GT3 NC TN MK-3682B (8 Wks) B5: GT3 NC TN MK-3682B + RBV (8 Wks) B6: GT3 NC TN MK-3682B (12 Wks) B7: GT3 NC TN MK-3682B + RBV (12 Wks) B8: GT3 NC TE MK-3682B (8 Wks) B9: GT3 NC TE MK-3682B + RBV (8 Wks) B10: GT3 NC TE MK-3682B (12 Wks) B11: GT3 NC TE MK-3682B + RBV (12 Wks) B12: GT3 NC TE MK-3682B (16 Wks) B13: GT3 C TN MK-3682B (12 Wks) B14: GT3 C TN MK-3682B + RBV (12 Wks) B15: GT3 C TN MK-3682B (16 Wks) B16: GT3 C TE MK-3682B (12 Wks) B17: GT3 C TE MK-3682B + RBV (12 Wks) B18: GT3 C TE MK-3682B (16 Wks) B19: GT3 C TE MK-3682B + RBV (16 Wks) B20: GT4 NC TN MK-3682B (8 Wks) B22: GT6 NC TN MK-3682B (12 Wks)
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 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   17/19 (89.47%)      1/2 (50.00%)      12/20 (60.00%)      1/1 (100.00%)      13/19 (68.42%)      3/3 (100.00%)      16/20 (80.00%)      2/2 (100.00%)      9/16 (56.25%)      30/36 (83.33%)      24/37 (64.86%)      32/35 (91.43%)      12/15 (80.00%)      12/14 (85.71%)      9/14 (64.29%)      13/15 (86.67%)      13/16 (81.25%)      9/13 (69.23%)      14/16 (87.50%)      12/14 (85.71%)      12/15 (80.00%)      11/14 (78.57%)      15/20 (75.00%)      21/25 (84.00%)      3/7 (42.86%)      3/4 (75.00%)    
Blood and lymphatic system disorders                                                     
Anaemia  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 1/37 (2.70%)  1 2/35 (5.71%)  2 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/13 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Haemolysis  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Haemolytic anaemia  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Lymph node pain  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Lymphadenopathy  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Cardiac disorders                                                     
Arrhythmia  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Atrial fibrillation  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 1/16 (6.25%)  1 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 1/25 (4.00%)  1 0/7 (0.00%)  0 0/4 (0.00%)  0
Bundle branch block right  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/13 (7.69%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Palpitations  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 2/36 (5.56%)  2 1/37 (2.70%)  2 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 1/13 (7.69%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 1/20 (5.00%)  1 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Sinus tachycardia  1  1/19 (5.26%)  1 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Tachycardia  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 0/37 (0.00%)  0 1/35 (2.86%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Ear and labyrinth disorders                                                     
Tinnitus  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 1/19 (5.26%)  1 0/3 (0.00%)  0 1/20 (5.00%)  1 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 1/37 (2.70%)  1 1/35 (2.86%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 1/7 (14.29%)  1 0/4 (0.00%)  0
Vertigo  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 1/37 (2.70%)  1 0/35 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/14 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/13 (0.00%)  0 1/16 (6.25%)  2 0/14 (0.00%)  0 1/15 (6.67%)  1 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Eye disorders                                                     
Dry eye  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Eye pain  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 1/4 (25.00%)  1
Ocular discomfort  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Pinguecula  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 1/16 (6.25%)  1 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Vision blurred  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/13 (7.69%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 1/25 (4.00%)  1 0/7 (0.00%)  0 0/4 (0.00%)  0
Visual impairment  1  1/19 (5.26%)  1 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Gastrointestinal disorders                                                     
Abdominal discomfort  1  1/19 (5.26%)  1 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 1/20 (5.00%)  1 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 1/35 (2.86%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/13 (7.69%)  1 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 1/14 (7.14%)  2 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Abdominal distension  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 1/20 (5.00%)  1 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 1/14 (7.14%)  1 0/15 (0.00%)  0 1/16 (6.25%)  2 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 1/20 (5.00%)  1 3/25 (12.00%)  3 0/7 (0.00%)  0 0/4 (0.00%)  0
Abdominal pain  1  1/19 (5.26%)  1 0/2 (0.00%)  0 1/20 (5.00%)  1 1/1 (100.00%)  1 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 1/37 (2.70%)  1 3/35 (8.57%)  3 0/15 (0.00%)  0 0/14 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 1/16 (6.25%)  2 0/13 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 3/20 (15.00%)  4 1/25 (4.00%)  1 0/7 (0.00%)  0 0/4 (0.00%)  0
Abdominal pain upper  1  1/19 (5.26%)  1 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 1/19 (5.26%)  1 0/3 (0.00%)  0 1/20 (5.00%)  1 0/2 (0.00%)  0 1/16 (6.25%)  1 2/36 (5.56%)  2 0/37 (0.00%)  0 1/35 (2.86%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 1/16 (6.25%)  1 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 2/14 (14.29%)  2 0/20 (0.00%)  0 1/25 (4.00%)  1 0/7 (0.00%)  0 0/4 (0.00%)  0
Aphthous ulcer  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 0/37 (0.00%)  0 1/35 (2.86%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Constipation  1  0/19 (0.00%)  0 0/2 (0.00%)  0 2/20 (10.00%)  2 0/1 (0.00%)  0 1/19 (5.26%)  1 2/3 (66.67%)  2 1/20 (5.00%)  1 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 1/37 (2.70%)  1 2/35 (5.71%)  2 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/13 (7.69%)  1 0/16 (0.00%)  0 1/14 (7.14%)  1 1/15 (6.67%)  1 1/14 (7.14%)  1 0/20 (0.00%)  0 2/25 (8.00%)  2 1/7 (14.29%)  1 0/4 (0.00%)  0
Dental caries  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Diarrhoea  1  2/19 (10.53%)  2 0/2 (0.00%)  0 1/20 (5.00%)  1 1/1 (100.00%)  1 0/19 (0.00%)  0 1/3 (33.33%)  1 3/20 (15.00%)  3 0/2 (0.00%)  0 2/16 (12.50%)  2 3/36 (8.33%)  3 5/37 (13.51%)  6 3/35 (8.57%)  4 2/15 (13.33%)  2 0/14 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 4/16 (25.00%)  4 0/13 (0.00%)  0 1/16 (6.25%)  2 1/14 (7.14%)  2 3/15 (20.00%)  3 1/14 (7.14%)  1 1/20 (5.00%)  1 1/25 (4.00%)  2 0/7 (0.00%)  0 0/4 (0.00%)  0
Diverticulum  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Dry mouth  1  1/19 (5.26%)  1 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 1/19 (5.26%)  1 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 0/37 (0.00%)  0 2/35 (5.71%)  2 2/15 (13.33%)  3 0/14 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Dyspepsia  1  0/19 (0.00%)  0 0/2 (0.00%)  0 1/20 (5.00%)  1 0/1 (0.00%)  0 1/19 (5.26%)  1 0/3 (0.00%)  0 1/20 (5.00%)  1 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 2/37 (5.41%)  2 3/35 (8.57%)  3 0/15 (0.00%)  0 1/14 (7.14%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/13 (7.69%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/20 (0.00%)  0 1/25 (4.00%)  1 0/7 (0.00%)  0 0/4 (0.00%)  0
Faeces soft  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 2/35 (5.71%)  2 1/15 (6.67%)  1 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Flatulence  1  2/19 (10.53%)  2 0/2 (0.00%)  0 2/20 (10.00%)  2 0/1 (0.00%)  0 1/19 (5.26%)  1 0/3 (0.00%)  0 1/20 (5.00%)  1 0/2 (0.00%)  0 0/16 (0.00%)  0 2/36 (5.56%)  2 0/37 (0.00%)  0 1/35 (2.86%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 2/16 (12.50%)  2 1/13 (7.69%)  1 0/16 (0.00%)  0 2/14 (14.29%)  2 1/15 (6.67%)  1 2/14 (14.29%)  2 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Frequent bowel movements  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 1/37 (2.70%)  1 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Gastritis  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 1/16 (6.25%)  1 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Gastrooesophageal reflux disease  1  0/19 (0.00%)  0 0/2 (0.00%)  0 1/20 (5.00%)  1 0/1 (0.00%)  0 1/19 (5.26%)  1 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 1/37 (2.70%)  1 0/35 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 2/16 (12.50%)  2 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/14 (0.00%)  0 0/20 (0.00%)  0 1/25 (4.00%)  1 0/7 (0.00%)  0 0/4 (0.00%)  0
Hiatus hernia  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Infrequent bowel movements  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Irritable bowel syndrome  1  1/19 (5.26%)  1 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Lip dry  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 1/3 (33.33%)  1 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Nausea  1  2/19 (10.53%)  3 0/2 (0.00%)  0 1/20 (5.00%)  1 1/1 (100.00%)  1 5/19 (26.32%)  6 0/3 (0.00%)  0 6/20 (30.00%)  6 0/2 (0.00%)  0 2/16 (12.50%)  2 6/36 (16.67%)  8 4/37 (10.81%)  5 5/35 (14.29%)  6 1/15 (6.67%)  1 3/14 (21.43%)  3 1/14 (7.14%)  1 2/15 (13.33%)  2 3/16 (18.75%)  3 2/13 (15.38%)  2 2/16 (12.50%)  3 3/14 (21.43%)  3 1/15 (6.67%)  1 2/14 (14.29%)  3 2/20 (10.00%)  2 4/25 (16.00%)  5 0/7 (0.00%)  0 0/4 (0.00%)  0
Oral pain  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 1/19 (5.26%)  1 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Paraesthesia oral  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 1/35 (2.86%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 1/14 (7.14%)  1 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Salivary hypersecretion  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 0/36 (0.00%)  0 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/13 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Tongue ulceration  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 0/19 (0.00%)  0 0/3 (0.00%)  0 0/20 (0.00%)  0 0/2 (0.00%)  0 0/16 (0.00%)  0 1/36 (2.78%)  1 0/37 (0.00%)  0 0/35 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/13 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0
Vomiting  1  0/19 (0.00%)  0 0/2 (0.00%)  0 0/20 (0.00%)  0 0/1 (0.00%)  0 1/19 (5.26%)  1 1/3 (33.33%)  1 3/20 (15.00%)  3 0/2 (0.00%)  0 2/16 (12.50%)  3 1/36 (2.78%)  1 3/37 (8.11%)  3 3/35 (8.57%)  3 0/15 (0.00%)  0 0/14 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/13 (7.69%)  1 1/16 (6.25%)  1 3/14 (21.43%)  3 0/15 (0.00%)  0 0/14 (0.00%)  0 0/20 (0.00%)  0 0/25 (0.00%)  0 0/7 (0.00%)  0 0/4 (0.00%)  0