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Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis (REMoxTB)

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ClinicalTrials.gov Identifier: NCT00864383
Recruitment Status : Completed
First Posted : March 18, 2009
Results First Posted : May 25, 2015
Last Update Posted : March 21, 2017
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
University College, London
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Sanofi
Information provided by (Responsible Party):
Global Alliance for TB Drug Development

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Tuberculosis
Intervention Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Enrollment 1931
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Period Title: Per- Protocol
Started 640 655 636
Completed 510 514 524
Not Completed 130 141 112
Period Title: Modified Intent to Treat
Started 640 655 636
Completed 555 568 551
Not Completed 85 87 85
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR (Isoniazid) Regimen 3 - 2EMRZ/2MR (Ethambutol) Total
Hide Arm/Group Description
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Total of all reporting groups
Overall Number of Baseline Participants 510 514 524 1548
Hide Baseline Analysis Population Description
Per protocol population
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
< 25 years 160 162 146 468
25-35 years 145 162 175 482
> 35 years 205 190 203 598
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
Female
154
  30.2%
163
  31.7%
155
  29.6%
472
  30.5%
Male
356
  69.8%
351
  68.3%
369
  70.4%
1076
  69.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
Black 238 210 237 685
Asian 160 154 161 475
Mixed race 111 148 126 385
Other 1 2 0 3
Weight group  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
< 40 kg 50 44 58 152
40-45 kg 80 90 82 252
> 45-55 kg 206 210 204 620
> 55-75 kg 161 158 174 493
> 75 kg 13 12 6 31
Smoking status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
Never 246 231 230 707
Past 119 111 134 364
Current 145 172 160 477
HIV positivity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
38 37 35 110
Drug resistance  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
Isoniazid 29 34 39 102
Pyrazinamide 14 7 6 27
Cavitation   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
368 357 367 1092
[1]
Measure Description: Chest cavitation based on blinded assessment of the chest radiograph.
Time to positivity on MGIT sputum culture   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 510 participants 514 participants 524 participants 1548 participants
≥ 5 days 266 263 258 787
< 5 days 229 239 254 722
Not available 15 12 12 39
[1]
Measure Description: Mycobacteria Growth Indicator Tube (MGIT) was used for the detection of mycobacteria.
1.Primary Outcome
Title Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ).
Hide Description The primary efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome). Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis. For the final 18 month study visit when both L-J samples were contaminated or missing, if the subject could not be brought back, liquid medium culture results were used in place of solid medium culture results.
Time Frame 18 months (within one year of completion of therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 510 514 524
Measure Type: Number
Unit of Measure: participants with failure or relapse
43 78 105
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regimen 1 - 2EHRZ/4HR (Control Regimen), Regimen 2 - 2MHRZ/2MHR
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Noninferiority was defined as a between-group difference of less than 6 percentage points in the upper boundary of the two-sided 97.5% Wald confidence interval for the difference in proportion of patients with an unfavorable outcome.
Method of Estimation Estimation Parameter Adjusted difference in proportions
Estimated Value 6.1
Confidence Interval (2-Sided) 97.5%
1.7 to 10.5
Estimation Comments Adjusted difference from control in proportion of unfavorable outcome - percentage points
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regimen 1 - 2EHRZ/4HR (Control Regimen), Regimen 3 - 2EMRZ/2MR
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Noninferiority was defined as a between-group difference of less than 6 percentage points in the upper boundary of the two-sided 97.5% Wald confidence interval for the proportion of patients with an unfavorable outcome.
Method of Estimation Estimation Parameter Adjusted difference from control
Estimated Value 11.4
Confidence Interval (2-Sided) 97.5%
6.7 to 16.1
Estimation Comments Adjusted difference from control in rate of unfavorable outcome- percentage points
2.Primary Outcome
Title Number of Patients With Grade 3 or 4 Adverse Events (Using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting)
Hide Description The number of participants includes all patients who had at least one grade 3 or 4 adverse event.
Time Frame 18 months (within one year of completion of therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all subjects who underwent randomization and who received at least on dose of study drug.
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 639 655 636
Measure Type: Number
Unit of Measure: participants with Grade 3 or 4 AEs
123 127 111
3.Secondary Outcome
Title Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).
Hide Description The secondary analysis of efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome) based on MGIT. Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis.
Time Frame 18 months (within one year of completion of therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 498 498 512
Measure Type: Number
Unit of Measure: participants with failure or relapse
65 98 131
4.Secondary Outcome
Title Number of Patients Who Are Culture Negative (Solid LJ Culture)
Hide Description Number of patients who are TB LJ culture negative at 8 weeks.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 422 457 458
Measure Type: Number
Unit of Measure: participants who are culture negative
352 394 401
5.Secondary Outcome
Title Number of Patients Who Are Culture Negative (Liquid MGIT Culture)
Hide Description Number of patients who are TB MGIT culture negative at 8 weeks.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 419 440 429
Measure Type: Number
Unit of Measure: participants who are culture negative
235 274 260
6.Secondary Outcome
Title Time to First Culture Negative Sputum Sample (LJ Solid Media)
Hide Description Culture negative for TB using LJ cultures.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients excluding late screen failures
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 600 617 604
Median (95% Confidence Interval)
Unit of Measure: Time to culture negative status / weeks
6.0
(6.0 to 6.1)
6.0
(5.1 to 6)
6.0
(5.7 to 6.0)
7.Secondary Outcome
Title Time to First Culture Negative Sputum Sample (MGIT Liquid Media)
Hide Description [Not Specified]
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients excluding late screen failures
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 600 617 604
Median (95% Confidence Interval)
Unit of Measure: Time to culture negative status / weeks
11.9
(8.1 to 12.0)
8.0
(8.0 to 9.9)
8.0
(8.0 to 8.1)
8.Secondary Outcome
Title Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.
Hide Description Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Unfavorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result (“isolated positive culture”) was followed by at least two negative culture results.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects.
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 640 655 636
Measure Type: Number
Unit of Measure: participants with unfavorable outcome
172 219 217
9.Secondary Outcome
Title Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.
Hide Description Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Favorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result (“isolated positive culture”) was followed by at least two negative culture results.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description:
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

Overall Number of Participants Analyzed 640 655 636
Measure Type: Number
Unit of Measure: participants with unfavorable outcome
87 132 132
Time Frame [Not Specified]
Adverse Event Reporting Description Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
 
Arm/Group Title Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Hide Arm/Group Description
  • Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by
  • Nine weeks of Isoniazid and Rifampicin only.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by
  • Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

  • Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by
  • Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by
  • Nine weeks of the Isoniazid placebo and the Rifampicin placebo

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin: Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg

All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.

All-Cause Mortality
Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   38/639 (5.95%)      46/655 (7.02%)      40/636 (6.29%)    
Gastrointestinal disorders       
Abdominal Distension  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Abdominal Mass  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Abdominal Pain  1  1/639 (0.16%)  1 0/655 (0.00%)  0 2/636 (0.31%)  2
Abdominal Pain Lower  1  0/639 (0.00%)  0 2/655 (0.31%)  3 0/636 (0.00%)  0
Abdominal Tenderness  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Acute Abdomen  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Ascites  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Diarrhoea  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Gastrointestinal Disorder  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Haematemesis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Haematochezia  1  1/639 (0.16%)  2 0/655 (0.00%)  0 0/636 (0.00%)  0
Nausea  1  1/639 (0.16%)  1 2/655 (0.31%)  2 2/636 (0.31%)  2
Pancreatitis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Peptic Ulcer Perforation  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Vomiting  1  1/639 (0.16%)  1 3/655 (0.46%)  3 6/636 (0.94%)  11
Infections and infestations       
Appendicitis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Diarrhoea Infectious  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Disseminated Tuberculosis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Gangrene  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Hepatitis B  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Investigations       
Aspartate Aminotransferase Increased  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Blood Bilirubin Increased  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Blood Creatinine Increased  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  1
Breath Sounds Abnormal  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Gamma- Glutamyltransferase Increased  1  2/639 (0.31%)  2 0/655 (0.00%)  0 2/636 (0.31%)  2
Haemoglobin Decreased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Hepatic Enzyme Increased  1  3/639 (0.47%)  3 3/655 (0.46%)  3 4/636 (0.63%)  4
International Normalised Ratio Increased  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Liver Function Test Abnormal  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Prothrombin Time prolonged  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Respiratory Rate Increased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Weight Decreased  1  2/639 (0.31%)  2 2/655 (0.31%)  2 2/636 (0.31%)  4
Respiratory, thoracic and mediastinal disorders       
Asphyxia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Asthma  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Bronchospasm  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Cough  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Dysphonia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Dyspnoea  1  5/639 (0.78%)  6 2/655 (0.31%)  2 6/636 (0.94%)  8
Haemoptysis  1  7/639 (1.10%)  8 6/655 (0.92%)  7 2/636 (0.31%)  2
Haemothorax  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Hydropneumothorax  1  0/639 (0.00%)  0 1/655 (0.15%)  3 0/636 (0.00%)  0
Hypoventilation  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Oropharyngeal Pain  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Pleural Effusion  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Pneumonia Aspiration  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Pneumothorax  1  2/639 (0.31%)  5 3/655 (0.46%)  3 3/636 (0.47%)  6
Rales  1  0/639 (0.00%)  0 2/655 (0.31%)  3 0/636 (0.00%)  0
Respiratory Distress  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Respiratory Failure  1  1/639 (0.16%)  1 1/655 (0.15%)  1 1/636 (0.16%)  1
Rhonchi  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Wheezing  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Regimen 1 - 2EHRZ/4HR (Control Regimen) Regimen 2 - 2MHRZ/2MHR Regimen 3 - 2EMRZ/2MR
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   507/639 (79.34%)      537/655 (81.98%)      522/636 (82.08%)    
Blood and lymphatic system disorders       
Abdominal Lymphadenopathy  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Anaemia  1  10/639 (1.56%)  17 13/655 (1.98%)  16 8/636 (1.26%)  11
Hypochromic Anaemia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Iron Deficiency Anaemia  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  2
Leukocytosis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Leukopenia  1  8/639 (1.25%)  13 9/655 (1.37%)  12 9/636 (1.42%)  12
Lymph Node Pain  1  2/639 (0.31%)  7 0/655 (0.00%)  0 0/636 (0.00%)  0
Lymphadenitis  1  1/639 (0.16%)  1 1/655 (0.15%)  2 0/636 (0.00%)  0
Lymphadenopathy  1  43/639 (6.73%)  61 44/655 (6.72%)  71 50/636 (7.86%)  68
Lymphopenia  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Microcytic Anaemia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Monocytosis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Neutropenia  1  4/639 (0.63%)  13 3/655 (0.46%)  6 2/636 (0.31%)  5
Neutrophilia  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Splenomegaly  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Thrombocytopenia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 2/636 (0.31%)  3
Thrombocytosis  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Cardiac disorders       
Arrhythmia  1  1/639 (0.16%)  1 1/655 (0.15%)  1 1/636 (0.16%)  1
Bradycardia  1  2/639 (0.31%)  3 0/655 (0.00%)  0 0/636 (0.00%)  0
Cardiac Failure  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Cardiac Failure Congestive  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Congestive Cardiomyopathy  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Cor Pulmonale  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Hyperdynamic Left Ventricle  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  1
Left Ventricular Hypertrophy  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Palpitations  1  1/639 (0.16%)  1 4/655 (0.61%)  5 2/636 (0.31%)  6
Pericardial Disease  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Sinus Tachycardia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Tachyarrhythmia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Tachycardia  1  40/639 (6.26%)  54 48/655 (7.33%)  71 39/636 (6.13%)  45
Ventricular Hypertrophy  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Ear and labyrinth disorders       
Auricular Swelling  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Cerumen Impaction  1  10/639 (1.56%)  13 5/655 (0.76%)  7 8/636 (1.26%)  8
Deafness  1  0/639 (0.00%)  0 2/655 (0.31%)  2 0/636 (0.00%)  0
Ear Canal Erythema  1  2/639 (0.31%)  2 1/655 (0.15%)  1 1/636 (0.16%)  1
Ear Discomfort  1  1/639 (0.16%)  1 1/655 (0.15%)  1 1/636 (0.16%)  2
Ear Pain  1  1/639 (0.16%)  1 3/655 (0.46%)  4 5/636 (0.79%)  7
Ear Pruritus  1  2/639 (0.31%)  2 1/655 (0.15%)  1 0/636 (0.00%)  0
Haematotympanum  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Hearing Impaired  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Hypoacusis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  2
Otorrhoea  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Tinnitus  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  1
Tympanic Membrane Hyperaemia  1  0/639 (0.00%)  0 4/655 (0.61%)  4 1/636 (0.16%)  1
Tympanic Membrane Perforation  1  2/639 (0.31%)  4 4/655 (0.61%)  4 3/636 (0.47%)  4
Tympanic Membrane Scarring  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Tympanosclerosis  1  1/639 (0.16%)  2 4/655 (0.61%)  6 1/636 (0.16%)  2
Vertigo  1  2/639 (0.31%)  2 3/655 (0.46%)  3 0/636 (0.00%)  0
Eye disorders       
Astigmatism  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Cataract  1  2/639 (0.31%)  2 0/655 (0.00%)  0 4/636 (0.63%)  4
Conjunctival Haemorrhage  1  0/639 (0.00%)  0 2/655 (0.31%)  2 0/636 (0.00%)  0
Conjunctival Hyperaemia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Conjunctival Irritation  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Conjunctival Pallor  1  1/639 (0.16%)  1 3/655 (0.46%)  3 3/636 (0.47%)  3
Conjunctivitis  1  2/639 (0.31%)  2 4/655 (0.61%)  6 3/636 (0.47%)  3
Conjunctivitis Allergic  1  3/639 (0.47%)  3 2/655 (0.31%)  2 3/636 (0.47%)  3
Corneal Opacity  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Dry Eye  1  1/639 (0.16%)  1 2/655 (0.31%)  2 0/636 (0.00%)  0
Eye Irritation  1  0/639 (0.00%)  0 2/655 (0.31%)  2 2/636 (0.31%)  2
Eye Oedema  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Eye Pain  1  4/639 (0.63%)  4 2/655 (0.31%)  2 4/636 (0.63%)  4
Eye Pruritus  1  4/639 (0.63%)  4 5/655 (0.76%)  6 8/636 (1.26%)  9
Eyelid Oedema  1  2/639 (0.31%)  2 0/655 (0.00%)  0 1/636 (0.16%)  1
Eyelids Pruritus  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Hypermetropia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Keratitis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  2
Lacrimation Increased  1  2/639 (0.31%)  2 1/655 (0.15%)  1 2/636 (0.31%)  2
Night Blindness  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Ocular Discomfort  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Ocular Hyperaemia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 2/636 (0.31%)  3
Ocular Icterus  1  2/639 (0.31%)  2 2/655 (0.31%)  2 1/636 (0.16%)  1
Photophobia  1  2/639 (0.31%)  2 2/655 (0.31%)  2 1/636 (0.16%)  1
Pterygium  1  2/639 (0.31%)  2 0/655 (0.00%)  0 0/636 (0.00%)  0
Scleral Hyperaemia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Scleritis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Uveitis  1  0/639 (0.00%)  0 1/655 (0.15%)  3 0/636 (0.00%)  0
Vision Blurred  1  10/639 (1.56%)  12 8/655 (1.22%)  8 9/636 (1.42%)  9
Visual Acuity Reduced  1  7/639 (1.10%)  9 16/655 (2.44%)  18 12/636 (1.89%)  12
Visual Impairment  1  4/639 (0.63%)  5 3/655 (0.46%)  3 1/636 (0.16%)  2
Vitreous Floaters  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Gastrointestinal disorders       
Abdominal Discomfort  1  1/639 (0.16%)  1 5/655 (0.76%)  6 7/636 (1.10%)  8
Abdominal Distension  1  3/639 (0.47%)  3 2/655 (0.31%)  3 4/636 (0.63%)  4
Abdominal Pain  1  12/639 (1.88%)  17 15/655 (2.29%)  20 15/636 (2.36%)  17
Abdominal Pain Lower  1  2/639 (0.31%)  2 1/655 (0.15%)  1 0/636 (0.00%)  0
Abdominal Pain Upper  1  10/639 (1.56%)  10 14/655 (2.14%)  14 7/636 (1.10%)  8
Abdominal Rigidity  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Abdominal Tenderness  1  5/639 (0.78%)  5 9/655 (1.37%)  13 6/636 (0.94%)  8
Anal Haemorrhage  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Anal Pruritus  1  1/639 (0.16%)  2 2/655 (0.31%)  3 0/636 (0.00%)  0
Ascites  1  0/639 (0.00%)  0 2/655 (0.31%)  3 0/636 (0.00%)  0
Chapped Lips  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Cheilitis  1  2/639 (0.31%)  2 2/655 (0.31%)  2 1/636 (0.16%)  1
Colitis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Constipation  1  10/639 (1.56%)  11 12/655 (1.83%)  17 3/636 (0.47%)  3
Dental Caries  1  6/639 (0.94%)  6 1/655 (0.15%)  1 7/636 (1.10%)  9
Diarrhoea  1  16/639 (2.50%)  18 38/655 (5.80%)  51 46/636 (7.23%)  59
Dyspepsia  1  10/639 (1.56%)  13 8/655 (1.22%)  8 5/636 (0.79%)  6
Dysphagia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  1
Epigastric Discomfort  1  3/639 (0.47%)  3 1/655 (0.15%)  1 2/636 (0.31%)  2
Faecal Volume Increased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Flatulence  1  0/639 (0.00%)  0 1/655 (0.15%)  3 0/636 (0.00%)  0
Food Poisoning  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Frequent Bowel Movements  1  2/639 (0.31%)  2 0/655 (0.00%)  0 1/636 (0.16%)  1
Gastritis  1  4/639 (0.63%)  5 7/655 (1.07%)  7 3/636 (0.47%)  4
Gastrointestinal Hypermotility  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Gastrointestinal Pain  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Gastrointestinal Sounds Abnormal  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Gastrooesophageal Reflux Disease  1  3/639 (0.47%)  3 1/655 (0.15%)  1 1/636 (0.16%)  1
Gingival Pain  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Gingival Recession  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Glossitis  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Haematemesis  1  2/639 (0.31%)  2 0/655 (0.00%)  0 2/636 (0.31%)  3
Haematochezia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Haemorrhoidal Haemorrhage  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Haemorrhoids  1  3/639 (0.47%)  4 1/655 (0.15%)  1 3/636 (0.47%)  3
Hyperchlorhydria  1  3/639 (0.47%)  3 3/655 (0.46%)  3 0/636 (0.00%)  0
Lip Blister  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Lip Swelling  1  1/639 (0.16%)  1 1/655 (0.15%)  1 1/636 (0.16%)  1
Lip Ulceration  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Lower Gastrointestinal Haemorrhage  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Melaena  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Mouth Haemorrhage  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Nausea  1  40/639 (6.26%)  49 39/655 (5.95%)  44 45/636 (7.08%)  50
Odynophagia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 2/636 (0.31%)  3
Oesophagitis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Oral Mucosal Discolouration  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  2
Oral Pain  1  2/639 (0.31%)  2 0/655 (0.00%)  0 0/636 (0.00%)  0
Paraesthesia Oral  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Parotid Gland Enlargement  1  0/639 (0.00%)  0 2/655 (0.31%)  2 0/636 (0.00%)  0
Peptic Ulcer  1  2/639 (0.31%)  3 2/655 (0.31%)  3 0/636 (0.00%)  0
Post-Tussive Vomiting  1  1/639 (0.16%)  1 4/655 (0.61%)  5 1/636 (0.16%)  2
Rectal Discharge  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Rectal Haemorrhage  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Rectal Tenesmus  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Salivary Gland Disorder  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Salivary Gland Pain  1  0/639 (0.00%)  0 0/655 (0.00%)  0 2/636 (0.31%)  2
Tongue Coated  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Tongue Disorder  1  0/639 (0.00%)  0 0/655 (0.00%)  0 2/636 (0.31%)  2
Tongue Haemorrhage  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Tongue Ulceration  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Toothache  1  5/639 (0.78%)  7 5/655 (0.76%)  6 4/636 (0.63%)  4
Vomiting  1  44/639 (6.89%)  56 70/655 (10.69%)  95 70/636 (11.01%)  92
General disorders       
Adhesion  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Asthenia  1  12/639 (1.88%)  14 10/655 (1.53%)  11 16/636 (2.52%)  19
Catheter Site Pain  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Chest Discomfort  1  2/639 (0.31%)  2 4/655 (0.61%)  4 1/636 (0.16%)  1
Chest Pain  1  60/639 (9.39%)  76 49/655 (7.48%)  57 55/636 (8.65%)  68
Chills  1  3/639 (0.47%)  3 1/655 (0.15%)  2 0/636 (0.00%)  0
Crepitations  1  5/639 (0.78%)  5 4/655 (0.61%)  4 7/636 (1.10%)  8
Face Oedema  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Fatigue  1  10/639 (1.56%)  12 21/655 (3.21%)  22 7/636 (1.10%)  7
Gait Disturbance  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Generalised Oedema  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Hernia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Hypothermia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Influenza Like Illness  1  2/639 (0.31%)  2 0/655 (0.00%)  0 0/636 (0.00%)  0
Local Swelling  1  5/639 (0.78%)  7 9/655 (1.37%)  10 2/636 (0.31%)  2
Malaise  1  2/639 (0.31%)  2 3/655 (0.46%)  3 3/636 (0.47%)  3
Mass  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Medical Device Pain  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  1
Mucosal Discolouration  1  0/639 (0.00%)  0 2/655 (0.31%)  2 0/636 (0.00%)  0
Non-Cardiac Chest Pain  1  20/639 (3.13%)  22 18/655 (2.75%)  20 23/636 (3.62%)  30
Oedema  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Oedema Peripheral  1  6/639 (0.94%)  7 2/655 (0.31%)  3 2/636 (0.31%)  4
Pain  1  10/639 (1.56%)  12 9/655 (1.37%)  14 10/636 (1.57%)  17
Pyrexia  1  58/639 (9.08%)  95 67/655 (10.23%)  103 84/636 (13.21%)  116
Tenderness  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Thirst  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Unevaluable Event  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Xerosis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Hepatobiliary disorders       
Hepatic Function Abnormal  1  5/639 (0.78%)  10 2/655 (0.31%)  3 2/636 (0.31%)  2
Hepatitis  1  0/639 (0.00%)  0 0/655 (0.00%)  0 2/636 (0.31%)  3
Hepatomegaly  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Hyperbilirubinaemia  1  2/639 (0.31%)  3 5/655 (0.76%)  7 2/636 (0.31%)  3
Jaundice  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Liver Tenderness  1  0/639 (0.00%)  0 2/655 (0.31%)  2 1/636 (0.16%)  2
Infections and infestations       
Abscess Neck  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Acarodermatitis  1  2/639 (0.31%)  3 1/655 (0.15%)  2 1/636 (0.16%)  1
Amoebic Dysentery  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Anal Abscess  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  1
Body Tinea  1  1/639 (0.16%)  1 5/655 (0.76%)  5 3/636 (0.47%)  4
Breast Abscess  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  2
Bronchitis  1  10/639 (1.56%)  10 3/655 (0.46%)  3 6/636 (0.94%)  6
Bronchitis Bacterial  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Bronchitis Viral  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Candida Infection  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Cellulitis  1  2/639 (0.31%)  2 0/655 (0.00%)  0 1/636 (0.16%)  1
Chest Wall Abscess  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Cystitis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Dermatitis Infected  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Dysentery  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Ear Infection  1  1/639 (0.16%)  1 2/655 (0.31%)  2 0/636 (0.00%)  0
Eye Infection  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Febrile Infection  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Folliculitis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Fungal Infection  1  2/639 (0.31%)  3 2/655 (0.31%)  2 2/636 (0.31%)  2
Fungal Skin Infection  1  5/639 (0.78%)  7 3/655 (0.46%)  3 3/636 (0.47%)  5
Furuncle  1  1/639 (0.16%)  2 0/655 (0.00%)  0 2/636 (0.31%)  3
Gastroenteritis  1  5/639 (0.78%)  6 1/655 (0.15%)  1 13/636 (2.04%)  14
Gastroenteritis Viral  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Genital Candidiasis  1  0/639 (0.00%)  0 2/655 (0.31%)  2 0/636 (0.00%)  0
Genital Herpes  1  1/639 (0.16%)  1 1/655 (0.15%)  1 1/636 (0.16%)  1
Giardiasis  1  1/639 (0.16%)  2 0/655 (0.00%)  0 0/636 (0.00%)  0
Gingival Abscess  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Helminthic Infection  1  1/639 (0.16%)  2 2/655 (0.31%)  2 2/636 (0.31%)  2
Herpes Zoster  1  2/639 (0.31%)  2 4/655 (0.61%)  5 1/636 (0.16%)  1
Hiv Infection  1  2/639 (0.31%)  3 1/655 (0.15%)  1 0/636 (0.00%)  0
Impetigo  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  2
Infected Dermal Cyst  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Infected Skin Ulcer  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Infection  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Influenza  1  15/639 (2.35%)  16 16/655 (2.44%)  16 17/636 (2.67%)  22
Laryngitis  1  3/639 (0.47%)  3 1/655 (0.15%)  1 3/636 (0.47%)  3
Lobar Pneumonia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 3/636 (0.47%)  3
Lower Respiratory Tract Infection  1  5/639 (0.78%)  5 10/655 (1.53%)  11 4/636 (0.63%)  4
Lower Respiratory Tract Infection Bacterial  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  2
Lung Abscess  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Lung Infection  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Malaria  1  15/639 (2.35%)  15 10/655 (1.53%)  11 9/636 (1.42%)  10
Molluscum Contagiosum  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Mycobacterium Fortuitum Infection  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Myringitis  1  1/639 (0.16%)  3 0/655 (0.00%)  0 0/636 (0.00%)  0
Nasopharyngitis  1  12/639 (1.88%)  14 15/655 (2.29%)  16 20/636 (3.14%)  21
Oesophageal Candidiasis  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Onychomycosis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Ophthalmic Herpes Zoster  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Oral Candidiasis  1  6/639 (0.94%)  9 12/655 (1.83%)  14 11/636 (1.73%)  13
Oral Hairy Leukoplakia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Oral Herpes  1  1/639 (0.16%)  1 1/655 (0.15%)  1 1/636 (0.16%)  1
Otitis Externa  1  0/639 (0.00%)  0 2/655 (0.31%)  3 0/636 (0.00%)  0
Otitis Media  1  2/639 (0.31%)  2 2/655 (0.31%)  3 0/636 (0.00%)  0
Otitis Media Chronic  1  1/639 (0.16%)  2 1/655 (0.15%)  1 0/636 (0.00%)  0
Pelvic Inflammatory Disease  1  1/639 (0.16%)  1 1/655 (0.15%)  2 1/636 (0.16%)  1
Pericarditis Tuberculous  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Pharyngitis  1  3/639 (0.47%)  3 7/655 (1.07%)  8 7/636 (1.10%)  7
Pharyngotonsillitis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Pneumocystis Jirovecii Pneumonia  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Pneumonia  1  6/639 (0.94%)  9 3/655 (0.46%)  5 7/636 (1.10%)  7
Pneumonia Bacterial  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  1
Pneumonia Haemophilus  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Pulmonary Tuberculosis  1  14/639 (2.19%)  14 24/655 (3.66%)  27 36/636 (5.66%)  37
Pulpitis Dental  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Pyelonephritis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Rash Pustular  1  0/639 (0.00%)  0 1/655 (0.15%)  1 2/636 (0.31%)  4
Respiratory Tract Infection  1  1/639 (0.16%)  1 2/655 (0.31%)  3 3/636 (0.47%)  3
Respiratory Tract Infection Viral  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Rhinitis  1  10/639 (1.56%)  11 13/655 (1.98%)  16 18/636 (2.83%)  21
Schistosomiasis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 2/636 (0.31%)  2
Schistosomiasis Bladder  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Septic Rash  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  8
Sinusitis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 2/636 (0.31%)  3
Subcutaneous Abscess  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Tinea Capitis  1  1/639 (0.16%)  1 4/655 (0.61%)  5 0/636 (0.00%)  0
Tinea Faciei  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Tinea Infection  1  2/639 (0.31%)  2 1/655 (0.15%)  1 1/636 (0.16%)  1
Tinea Pedis  1  2/639 (0.31%)  2 0/655 (0.00%)  0 3/636 (0.47%)  4
Tinea Versicolour  1  1/639 (0.16%)  1 3/655 (0.46%)  3 4/636 (0.63%)  5
Tonsillitis  1  2/639 (0.31%)  2 0/655 (0.00%)  0 2/636 (0.31%)  2
Tooth Abscess  1  1/639 (0.16%)  2 2/655 (0.31%)  2 1/636 (0.16%)  2
Tooth Infection  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Tuberculosis  1  3/639 (0.47%)  3 11/655 (1.68%)  11 8/636 (1.26%)  9
Tuberculosis Gastrointestinal  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Typhoid Fever  1  3/639 (0.47%)  3 0/655 (0.00%)  0 1/636 (0.16%)  1
Upper Respiratory Tract Infection  1  24/639 (3.76%)  27 20/655 (3.05%)  23 20/636 (3.14%)  24
Upper Respiratory Tract Infection Bacterial  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Urinary Tract Infection  1  8/639 (1.25%)  9 7/655 (1.07%)  8 11/636 (1.73%)  12
Vaginitis Bacterial  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Varicella  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Viral Infection  1  2/639 (0.31%)  2 0/655 (0.00%)  0 0/636 (0.00%)  0
Viral Upper Respiratory Tract Infection  1  7/639 (1.10%)  13 6/655 (0.92%)  11 7/636 (1.10%)  11
Vulvovaginal Candidiasis  1  5/639 (0.78%)  8 7/655 (1.07%)  9 6/636 (0.94%)  8
Vulvovaginitis  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Wound Infection  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Wound Sepsis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Injury, poisoning and procedural complications       
Accident  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Animal Bite  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Ankle Fracture  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Contusion  1  3/639 (0.47%)  3 1/655 (0.15%)  1 4/636 (0.63%)  4
Excoriation  1  2/639 (0.31%)  2 2/655 (0.31%)  2 2/636 (0.31%)  2
Eyelid Injury  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Fall  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Fibula Fracture  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Foreign Body  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Foreign Body In Eye  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Hand Fracture  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Human Bite  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Humerus Fracture  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Incorrect Dose Administered  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Injury Corneal  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Jaw Fracture  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Joint Injury  1  0/639 (0.00%)  0 2/655 (0.31%)  3 0/636 (0.00%)  0
Laceration  1  0/639 (0.00%)  0 2/655 (0.31%)  2 4/636 (0.63%)  5
Ligament Sprain  1  0/639 (0.00%)  0 2/655 (0.31%)  4 2/636 (0.31%)  2
Lip Injury  1  1/639 (0.16%)  1 0/655 (0.00%)  0 2/636 (0.31%)  2
Muscle Strain  1  1/639 (0.16%)  1 3/655 (0.46%)  3 1/636 (0.16%)  1
Periorbital Contusion  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Rib Fracture  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Road Traffic Accident  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Scar  1  2/639 (0.31%)  2 1/655 (0.15%)  1 0/636 (0.00%)  0
Skeletal Injury  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Soft Tissue Injury  1  1/639 (0.16%)  1 0/655 (0.00%)  0 3/636 (0.47%)  3
Stab Wound  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Subdural Haematoma  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Thermal Burn  1  2/639 (0.31%)  2 1/655 (0.15%)  1 1/636 (0.16%)  1
Tibia Fracture  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Tooth Fracture  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Wound  1  0/639 (0.00%)  0 2/655 (0.31%)  2 1/636 (0.16%)  1
Investigations       
Activated Partial Thromboplastin Time Prolonged  1  10/639 (1.56%)  13 10/655 (1.53%)  13 13/636 (2.04%)  16
Alanine Aminotransferase Abnormal  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Alanine Aminotransferase Decreased  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Alanine Aminotransferase Increased  1  25/639 (3.91%)  37 30/655 (4.58%)  39 16/636 (2.52%)  24
Amylase Increased  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Aspartate Aminotransferase Increased  1  28/639 (4.38%)  41 35/655 (5.34%)  47 24/636 (3.77%)  31
Blood Albumin Decreased  1  1/639 (0.16%)  3 2/655 (0.31%)  3 2/636 (0.31%)  2
Blood Bilirubin Increased  1  4/639 (0.63%)  4 9/655 (1.37%)  14 2/636 (0.31%)  6
Blood Creatine Increased  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Blood Creatinine Decreased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  2
Blood Creatinine Increased  1  7/639 (1.10%)  8 15/655 (2.29%)  17 7/636 (1.10%)  10
Blood Glucose Abnormal  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Blood Glucose Increased  1  2/639 (0.31%)  4 3/655 (0.46%)  9 0/636 (0.00%)  0
Blood Potassium Decreased  1  0/639 (0.00%)  0 3/655 (0.46%)  3 4/636 (0.63%)  5
Blood Potassium Increased  1  0/639 (0.00%)  0 2/655 (0.31%)  2 0/636 (0.00%)  0
Blood Pressure Decreased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Blood Pressure Diastolic Decreased  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Blood Pressure Diastolic Increased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  2
Blood Pressure Increased  1  6/639 (0.94%)  7 6/655 (0.92%)  7 7/636 (1.10%)  8
Blood Pressure Systolic Decreased  1  0/639 (0.00%)  0 1/655 (0.15%)  1 2/636 (0.31%)  2
Blood Pressure Systolic Increased  1  2/639 (0.31%)  2 1/655 (0.15%)  4 0/636 (0.00%)  0
Blood Sodium Decreased  1  4/639 (0.63%)  9 2/655 (0.31%)  2 0/636 (0.00%)  0
Blood Sodium Increased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 4/636 (0.63%)  5
Blood Urea Increased  1  1/639 (0.16%)  1 1/655 (0.15%)  2 0/636 (0.00%)  0
Blood Uric Acid Increased  1  2/639 (0.31%)  2 1/655 (0.15%)  1 0/636 (0.00%)  0
Body Temperature Increased  1  2/639 (0.31%)  2 0/655 (0.00%)  0 0/636 (0.00%)  0
Breath Sounds Abnormal  1  7/639 (1.10%)  9 9/655 (1.37%)  10 5/636 (0.79%)  6
Cardiac Murmur  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Cd4 Lymphocytes Decreased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Chest X-Ray Abnormal  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Coagulation Test Abnormal  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Colour Vision Tests Abnormal  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Creatinine Renal Clearance Decreased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Gamma-Glutamyltransferase Increased  1  2/639 (0.31%)  4 1/655 (0.15%)  1 0/636 (0.00%)  0
Gastrointestinal Examination Abnormal  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Glucose Urine Present  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Haemoglobin Decreased  1  13/639 (2.03%)  24 18/655 (2.75%)  29 20/636 (3.14%)  28
Heart Rate Increased  1  2/639 (0.31%)  2 0/655 (0.00%)  0 1/636 (0.16%)  1
Heart Rate Irregular  1  3/639 (0.47%)  3 1/655 (0.15%)  1 1/636 (0.16%)  3
Heart Sounds Abnormal  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Hepatic Enzyme Abnormal  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Hepatic Enzyme Increased  1  22/639 (3.44%)  36 18/655 (2.75%)  30 11/636 (1.73%)  17
International Normalised Ratio Abnormal  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
International Normalised Ratio Increased  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Liver Function Test Abnormal  1  2/639 (0.31%)  4 0/655 (0.00%)  0 0/636 (0.00%)  0
Liver Palpable Subcostal  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  2
Lymph Node Palpable  1  0/639 (0.00%)  0 0/655 (0.00%)  0 2/636 (0.31%)  2
Neutrophil Count Decreased  1  1/639 (0.16%)  1 3/655 (0.46%)  3 0/636 (0.00%)  0
Neutrophil Percentage Decreased  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Ophthalmological Examination Abnormal  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Percussion Test Abnormal  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Platelet Count Decreased  1  5/639 (0.78%)  5 3/655 (0.46%)  6 4/636 (0.63%)  4
Prothrombin Level Increased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Prothrombin Time Abnormal  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Prothrombin Time Prolonged  1  11/639 (1.72%)  15 13/655 (1.98%)  16 20/636 (3.14%)  30
Pulmonary Physical Examination Abnormal  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Red Blood Cell Sedimentation Rate Increased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Respiratory Rate Increased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Transaminases Increased  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Urine Analysis Abnormal  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Urine Cytology Abnormal  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Urine Leukocyte Esterase Positive  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Weight Decreased  1  62/639 (9.70%)  83 70/655 (10.69%)  85 72/636 (11.32%)  77
White Blood Cell Count Decreased  1  2/639 (0.31%)  3 0/655 (0.00%)  0 1/636 (0.16%)  2
White Blood Cell Count Increased  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Metabolism and nutrition disorders       
Abnormal Loss Of Weight  1  15/639 (2.35%)  22 20/655 (3.05%)  23 16/636 (2.52%)  18
Cachexia  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Decreased Appetite  1  45/639 (7.04%)  54 33/655 (5.04%)  35 45/636 (7.08%)  50
Dehydration  1  2/639 (0.31%)  3 0/655 (0.00%)  0 1/636 (0.16%)  1
Diabetes Mellitus  1  6/639 (0.94%)  10 7/655 (1.07%)  9 9/636 (1.42%)  13
Diabetes Mellitus Inadequate Control  1  0/639 (0.00%)  0 1/655 (0.15%)  2 1/636 (0.16%)  1
Electrolyte Imbalance  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Hypercholesterolaemia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 1/636 (0.16%)  1
Hyperglycaemia  1  3/639 (0.47%)  3 3/655 (0.46%)  6 2/636 (0.31%)  5
Hyperkalaemia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 3/636 (0.47%)  3
Hypernatraemia  1  1/639 (0.16%)  1 1/655 (0.15%)  1 1/636 (0.16%)  1
Hyperuricaemia  1  3/639 (0.47%)  3 1/655 (0.15%)  3 1/636 (0.16%)  1
Hypoglycaemia  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Hypokalaemia  1  1/639 (0.16%)  1 3/655 (0.46%)  4 1/636 (0.16%)  1
Hyponatraemia  1  4/639 (0.63%)  5 5/655 (0.76%)  6 1/636 (0.16%)  1
Iron Deficiency  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Metabolic Acidosis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Polydipsia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Vitamin B Complex Deficiency  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  10/639 (1.56%)  182 12/655 (1.83%)  177 10/636 (1.57%)  162
Arthritis  1  6/639 (0.94%)  7 6/655 (0.92%)  12 1/636 (0.16%)  1
Arthropathy  1  3/639 (0.47%)  3 4/655 (0.61%)  7 2/636 (0.31%)  2
Arthrotoxicity  1  1/639 (0.16%)  2 3/655 (0.46%)  5 4/636 (0.63%)  7
Back Pain  1  19/639 (2.97%)  26 20/655 (3.05%)  24 20/636 (3.14%)  22
Bursitis  1  1/639 (0.16%)  2 1/655 (0.15%)  1 1/636 (0.16%)  1
Chondrotoxicity  1  1/639 (0.16%)  1 3/655 (0.46%)  3 1/636 (0.16%)  1
Clubbing  1  2/639 (0.31%)  2 2/655 (0.31%)  3 0/636 (0.00%)  0
Costochondritis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Fibromyalgia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 1/636 (0.16%)  1
Finger Deformity  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Flank Pain  1  1/639 (0.16%)  1 1/655 (0.15%)  1 4/636 (0.63%)  4
Gouty Arthritis  1  2/639 (0.31%)  4 0/655 (0.00%)  0 1/636 (0.16%)  1
Joint Range Of Motion Decreased  1  1/639 (0.16%)  2 1/655 (0.15%)  1 1/636 (0.16%)  1
Joint Stiffness  1  1/639 (0.16%)  1 2/655 (0.31%)  3 1/636 (0.16%)  1
Joint Swelling  1  5/639 (0.78%)  6 4/655 (0.61%)  5 6/636 (0.94%)  9
Ligament Pain  1  2/639 (0.31%)  3 2/655 (0.31%)  3 0/636 (0.00%)  0
Metatarsalgia  1  2/639 (0.31%)  3 0/655 (0.00%)  0 0/636 (0.00%)  0
Muscle Atrophy  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Muscle Fatigue  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Muscle Spasms  1  10/639 (1.56%)  11 6/655 (0.92%)  10 4/636 (0.63%)  4
Muscle Swelling  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Muscular Weakness  1  3/639 (0.47%)  4 5/655 (0.76%)  5 2/636 (0.31%)  2
Musculoskeletal Chest Pain  1  1/639 (0.16%)  1 3/655 (0.46%)  5 0/636 (0.00%)  0
Musculoskeletal Discomfort  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Musculoskeletal Disorder  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Musculoskeletal Pain  1  12/639 (1.88%)  17 11/655 (1.68%)  12 7/636 (1.10%)  8
Musculoskeletal Stiffness  1  4/639 (0.63%)  5 4/655 (0.61%)  6 1/636 (0.16%)  1
Myalgia  1  14/639 (2.19%)  15 28/655 (4.27%)  41 21/636 (3.30%)  25
Myopathy  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Myositis  1  1/639 (0.16%)  1 0/655 (0.00%)  0 2/636 (0.31%)  2
Neck Pain  1  3/639 (0.47%)  4 6/655 (0.92%)  6 2/636 (0.31%)  3
Osteoarthritis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Pain In Extremity  1  32/639 (5.01%)  44 27/655 (4.12%)  38 29/636 (4.56%)  43
Periarthritis  1  3/639 (0.47%)  4 0/655 (0.00%)  0 0/636 (0.00%)  0
Polyarthritis  1  0/639 (0.00%)  0 1/655 (0.15%)  3 0/636 (0.00%)  0
Sensation Of Heaviness  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Spinal Pain  1  1/639 (0.16%)  2 0/655 (0.00%)  0 0/636 (0.00%)  0
Synovial Cyst  1  1/639 (0.16%)  1 1/655 (0.15%)  1 0/636 (0.00%)  0
Tendon Disorder  1  2/639 (0.31%)  3 5/655 (0.76%)  6 4/636 (0.63%)  4
Tendon Pain  1  3/639 (0.47%)  3 4/655 (0.61%)  4 3/636 (0.47%)  3
Tendonitis  1  1/639 (0.16%)  1 2/655 (0.31%)  3 1/636 (0.16%)  1
Trigger Finger  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Upper Extremity Mass  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Anogenital Warts  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Penile Wart  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Pharyngeal Neoplasm Benign  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Thyroid Neoplasm  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Nervous system disorders       
Ageusia  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Burning Sensation  1  2/639 (0.31%)  3 3/655 (0.46%)  3 0/636 (0.00%)  0
Coma  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Convulsion  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Dizziness  1  15/639 (2.35%)  17 16/655 (2.44%)  25 26/636 (4.09%)  32
Dizziness Postural  1  0/639 (0.00%)  0 2/655 (0.31%)  2 0/636 (0.00%)  0
Dysgeusia  1  0/639 (0.00%)  0 1/655 (0.15%)  2 0/636 (0.00%)  0
Epilepsy  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Headache  1  35/639 (5.48%)  44 39/655 (5.95%)  45 52/636 (8.18%)  63
Hemiparesis  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Hemiplegia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Hyperaesthesia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Hyperreflexia  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Hypoaesthesia  1  8/639 (1.25%)  14 8/655 (1.22%)  9 12/636 (1.89%)  19
Lethargy  1  0/639 (0.00%)  0 0/655 (0.00%)  0 3/636 (0.47%)  3
Loss Of Consciousness  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Memory Impairment  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Migraine  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Neuralgia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Neuritis  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Neuropathy Peripheral  1  13/639 (2.03%)  16 6/655 (0.92%)  6 11/636 (1.73%)  14
Paraesthesia  1  8/639 (1.25%)  12 10/655 (1.53%)  13 3/636 (0.47%)  5
Parosmia  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Post Herpetic Neuralgia  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Restless Legs Syndrome  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Sciatica  1  0/639 (0.00%)  0 0/655 (0.00%)  0 2/636 (0.31%)  3
Sensory Disturbance  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Somnolence  1  6/639 (0.94%)  6 5/655 (0.76%)  8 7/636 (1.10%)  7
Syncope  1  2/639 (0.31%)  2 1/655 (0.15%)  1 2/636 (0.31%)  2
Tension Headache  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Tremor  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Visual Field Defect  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Pregnancy, puerperium and perinatal conditions       
Abortion Threatened  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Pregnancy  1  1/639 (0.16%)  1 4/655 (0.61%)  4 0/636 (0.00%)  0
Psychiatric disorders       
Anxiety  1  2/639 (0.31%)  2 2/655 (0.31%)  2 5/636 (0.79%)  5
Anxiety Disorder  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Confusional State  1  0/639 (0.00%)  0 1/655 (0.15%)  1 2/636 (0.31%)  3
Depression  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Hallucination  1  0/639 (0.00%)  0 1/655 (0.15%)  1 0/636 (0.00%)  0
Initial Insomnia  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Insomnia  1  12/639 (1.88%)  16 6/655 (0.92%)  6 6/636 (0.94%)  6
Nervousness  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Premature Ejaculation  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Psychotic Disorder  1  1/639 (0.16%)  1 0/655 (0.00%)  0 0/636 (0.00%)  0
Sleep Disorder  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Tension  1  0/639 (0.00%)  0 0/655 (0.00%)  0 1/636 (0.16%)  1
Renal and urinary disorders       
Bilirubinuria  1  0/639 (0.00%)  0 5/655 (0.76%)  5 0/636 (0.00%)  0
Dysuria  1  6/639 (0.94%)  7