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Evaluation of SQ109, High-dose Rifampicin, and Moxifloxacin in Adults With Smear-positive Pulmonary TB in a MAMS Design

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ClinicalTrials.gov Identifier: NCT01785186
Recruitment Status : Completed
First Posted : February 7, 2013
Results First Posted : September 20, 2017
Last Update Posted : September 20, 2017
Sponsor:
Collaborators:
Sequella, Inc.
European and Developing Countries Clinical Trials Partnership (EDCTP)
German Federal Ministry of Education and Research
Medical Research Council
Radboud University
Information provided by (Responsible Party):
Michael Hoelscher, Ludwig-Maximilians - University of Munich

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Tuberculosis, Pulmonary
Interventions Drug: SQ109
Drug: Rifampicin
Drug: Moxifloxacin
Drug: isoniazid
Drug: pyrazinamide
Drug: ethambutol
Dietary Supplement: pyridoxine
Enrollment 365
Recruitment Details  
Pre-assignment Details  
Arm/Group Title HRZQ Arm 1 (R35) HR20ZQ HR20ZM HRZE
Hide Arm/Group Description

Arm 2 (Q): HRZQ isoniazid, rifampicin standard, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 1 (R35): HR35ZE isoniazid, rifampicin 35 mg/kg, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Arm 3 (R20Q): HR20ZQ isoniazid, rifampicin 20 mg/kg, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 4 (R20M): HR20ZM isoniazid, rifampicin 20 mg/kg, pyrazinamide, moxifloxacin 400 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

HRZE: Isoniazid, rifampicin standard, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

Moxifloxacin: Moxifloxacin 400mg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Period Title: Overall Study
Started 59 63 57 63 123
Completed 53 57 52 58 117
Not Completed 6 6 5 5 6
Arm/Group Title HRZQ Arm 1 (R35) HR20ZQ HR20ZM HRZE Total
Hide Arm/Group Description

Arm 2 (Q): HRZQ isoniazid, rifampicin standard, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 1 (R35): HR35ZE isoniazid, rifampicin 35 mg/kg, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Arm 3 (R20Q): HR20ZQ isoniazid, rifampicin 20 mg/kg, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 4 (R20M): HR20ZM isoniazid, rifampicin 20 mg/kg, pyrazinamide, moxifloxacin 400 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

HRZE: Isoniazid, rifampicin standard, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

Moxifloxacin: Moxifloxacin 400mg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Total of all reporting groups
Overall Number of Baseline Participants 59 63 57 63 123 365
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 59 participants 63 participants 57 participants 63 participants 123 participants 365 participants
32
(25 to 40)
33
(23 to 40)
34
(27 to 41)
31
(24 to 38)
34
(26 to 41)
32.9
(23.8 to 40.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants 63 participants 57 participants 63 participants 123 participants 365 participants
Female
21
  35.6%
21
  33.3%
12
  21.1%
24
  38.1%
29
  23.6%
107
  29.3%
Male
38
  64.4%
42
  66.7%
45
  78.9%
39
  61.9%
94
  76.4%
258
  70.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants 63 participants 57 participants 63 participants 123 participants 365 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
50
  84.7%
51
  81.0%
50
  87.7%
48
  76.2%
101
  82.1%
300
  82.2%
White
0
   0.0%
1
   1.6%
1
   1.8%
0
   0.0%
0
   0.0%
2
   0.5%
More than one race
9
  15.3%
11
  17.5%
6
  10.5%
15
  23.8%
19
  15.4%
60
  16.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   2.4%
3
   0.8%
HIV Positive Participants  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 59 participants 63 participants 57 participants 63 participants 123 participants 365 participants
5 4 3 3 9 24
1.Primary Outcome
Title Sputum Culture Conversion (2 Negative Cultures) Using Liquid Media
Hide Description From enrollment, the time to stable culture conversion (2 consecutive negative weekly cultures) in liquid media.
Time Frame 0 - 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intention to treat analysis
Arm/Group Title Arm 1 (R35) HRZQ HR20ZQ HR20ZM HRZE
Hide Arm/Group Description:

Arm 1 (R35): HR35ZE isoniazid, rifampicin 35 mg/kg, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Arm 2 (Q): HRZQ isoniazid, rifampicin standard, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 3 (R20Q): HR20ZQ isoniazid, rifampicin 20 mg/kg, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 4 (R20M): HR20ZM isoniazid, rifampicin 20 mg/kg, pyrazinamide, moxifloxacin 400 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

HRZE: Isoniazid, rifampicin standard, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

Moxifloxacin: Moxifloxacin 400mg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Overall Number of Participants Analyzed 63 58 56 63 123
Median (Inter-Quartile Range)
Unit of Measure: days
48
(34 to 69)
63
(48 to 83)
66
(41 to 83)
55
(41 to 69)
62
(41 to 83)
2.Secondary Outcome
Title Frequency of Adverse Events
Hide Description All Adverse Events (AE), and AEs considered to be drug-related will coded using standard AE dictionaries.
Time Frame 0 - 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm 1 (R35) HRZQ HR20ZQ HR20ZM HRZE
Hide Arm/Group Description:

Arm 1 (R35): HR35ZE isoniazid, rifampicin 35 mg/kg, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Arm 2 (Q): HRZQ isoniazid, rifampicin standard, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 3 (R20Q): HR20ZQ isoniazid, rifampicin 20 mg/kg, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 4 (R20M): HR20ZM isoniazid, rifampicin 20 mg/kg, pyrazinamide, moxifloxacin 400 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

HRZE: Isoniazid, rifampicin standard, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

Moxifloxacin: Moxifloxacin 400mg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Overall Number of Participants Analyzed 63 58 56 63 123
Measure Type: Number
Unit of Measure: participants
Number of Patients with at least 1 AE 53 49 42 49 92
Number of patients with at least 1 SAE 4 4 5 4 6
3.Secondary Outcome
Title Mycobacteriology Identification and Characterization by PCR and MIC
Hide Description

Cultures grown from the screening period, and the last sputum sample with mycobacteriological growth will be assessed as follows:

  • Identification of M. tuberculosis complex and RIF resistance by PCR (GeneXpert MTB/RIF®),
  • First-line drug susceptibility testing of the M. tuberculosis isolates using the MGIT system for sensitivity to rifampicin; isoniazid, pyrazinamide, moxifloxacin or ethambutol.
  • Minimum inhibitory concentrations (MIC) of SQ109, rifampicin and moxifloxacin.
  • Typing of the infecting strain(s) by molecular methods.
Time Frame 0 - 12 weeks
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Pharmacokinetics Including AUC, Cl, t1/2, Vd, and Protein Binding
Hide Description

Pharmacokinetic parameters will be assessed for rifampicin, moxifloxacin and SQ109:

  • area under the plasma concentration curve from dosing to the end of the dosing interval (AUC 0-24) (in h*ng/mL)
  • the observed maximum concentration (Cmax( (in ng/mL)
  • time to reach Cmax (Tmax)(in hours)
  • the minimum observed plasma concentration 24 hours following the last dose (Cmin) (in hours),
  • clearance (Cl) (in mL/minute),
  • volume of distribution (Vd) (in L),
  • elimination half-life (T1/2,) (in hours)
  • free (protein-unbound) fraction (for rifampicin only) (in percent).
Time Frame 0 - 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population
Arm/Group Title HRZQ Arm 1 (R35) HR20ZQ HR20ZM HRZE
Hide Arm/Group Description:

Arm 2 (Q): HRZQ isoniazid, rifampicin standard, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 1 (R35): HR35ZE isoniazid, rifampicin 35 mg/kg, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Arm 3 (R20Q): HR20ZQ isoniazid, rifampicin 20 mg/kg, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 4 (R20M): HR20ZM isoniazid, rifampicin 20 mg/kg, pyrazinamide, moxifloxacin 400 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

HRZE: Isoniazid, rifampicin standard, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

Moxifloxacin: Moxifloxacin 400mg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Overall Number of Participants Analyzed 19 20 19 19 19
Geometric Mean (Full Range)
Unit of Measure: Rifampicin AUC(mg*h/l)
17.4
(4.3 to 45.3)
170
(103 to 266)
68.3
(38.5 to 149)
57.8
(15 to 121)
24.2
(11.9 to 52.5)
5.Secondary Outcome
Title Pharmacodynamics Including AUC0-24/MIC (h*ng/mL) and Cmax/MIC (ng/mL)
Hide Description By combining pharmacokinetic parameters and MIC values (see below), the pharmacodynamic indices AUC0-24/MIC (h*ng/mL) and Cmax/MIC (ng/mL) will be calculated for individual patients for experimental drugs administered. Pharmacokinetic parameters and pharmacodynamic indices will be related to efficacy and safety/tolerability endpoints.
Time Frame 0 - 12 weeks
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Time to First Negative Culture on Liquid and Solid Media
Hide Description Time to a convert to a single negative culture on liquid and solid media
Time Frame 0 - 12 weeks
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Proportion of Negative Sputum Cultures
Hide Description Proportion of patients converting to negative sputum culture (2 consecutive weekly cultures) in liquid and solid media
Time Frame 0 - 12 weeks
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Rate of Change in Time to Positivity
Hide Description Rate of change in time to positivity in BD MGIT 960® liquid culture
Time Frame 0 - 12 weeks
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Rate of Change in Quantitative PCR During Therapy
Hide Description GeneXpert MTB/RIF (Xpert) quantitative PCR results (counts per week
Time Frame 0 - 12 weeks
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Occurence of Treatment Failure (Relapse or Emergence of Drug-resistance)
Hide Description Frequency of treatment failures (number of patients with relapse and/or development of drug resistance) will be recorded
Time Frame 0 - 12 weeks
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Changes in Baseline Laboratory Safety Parameters During Treatment and Follow-up
Hide Description Frequency tables will be generated for visual acuity tests, 12 lead ECGs, clinical chemistry metrics, haematology, and urinalysis
Time Frame 0 - 12 weeks
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title HRZQ Arm 1 (R35) HR20ZQ HR20ZM HRZE
Hide Arm/Group Description

Arm 2 (Q): HRZQ isoniazid, rifampicin standard, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 1 (R35): HR35ZE isoniazid, rifampicin 35 mg/kg, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

Arm 3 (R20Q): HR20ZQ isoniazid, rifampicin 20 mg/kg, pyrazinamide, SQ109 300 mg

SQ109: SQ109 300 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

Arm 4 (R20M): HR20ZM isoniazid, rifampicin 20 mg/kg, pyrazinamide, moxifloxacin 400 mg

Rifampicin: Rifampicin 10 to 35 mg/kg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

pyridoxine: pyridoxine 25 mg

HRZE: Isoniazid, rifampicin standard, pyrazinamide, ethambutol

Rifampicin: Rifampicin 10 to 35 mg/kg

Moxifloxacin: Moxifloxacin 400mg

isoniazid: isoniazid 75 mg

pyrazinamide: pyrazinamide 400 mg

ethambutol: ethambutol 275 mg

pyridoxine: pyridoxine 25 mg

All-Cause Mortality
HRZQ Arm 1 (R35) HR20ZQ HR20ZM HRZE
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
HRZQ Arm 1 (R35) HR20ZQ HR20ZM HRZE
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/59 (6.78%)      4/63 (6.35%)      5/57 (8.77%)      4/63 (6.35%)      6/123 (4.88%)    
Blood and lymphatic system disorders           
haemoptysis  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Cardiac disorders           
Death  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Endocrine disorders           
hyper osmolar hyperglycaemia state (diabetic melitus) grade 4  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Gastrointestinal disorders           
Upper gastrointestinal bleeding  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Hepatobiliary disorders           
Intrahepatic cholestasis  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Liver failure  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Immune system disorders           
Fever - hospitalization  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthritis of ankles  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Cerebral fractures due to post motor vehicle accident  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Nervous system disorders           
Seizure  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Psychiatric disorders           
Psychosis  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Parasuicide  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Parasuicide  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Respiratory, thoracic and mediastinal disorders           
Acute Dyspnoea  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
pulmonary embolism  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
left pneumothorax  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Resiratory insufficiency secondary to psnumonia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Pneumothorax  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
pulmonary embolism  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Community accuired pneumonia  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Multi drug resistant TB  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Vascular disorders           
Deep vein thrombosis  1/59 (1.69%)  1 0/63 (0.00%)  0 3/57 (5.26%)  3 0/63 (0.00%)  0 0/123 (0.00%)  0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
HRZQ Arm 1 (R35) HR20ZQ HR20ZM HRZE
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   49/59 (83.05%)      53/63 (84.13%)      42/57 (73.68%)      49/63 (77.78%)      92/123 (74.80%)    
Blood and lymphatic system disorders           
Anaemia  2/59 (3.39%)  2 2/63 (3.17%)  2 0/57 (0.00%)  0 2/63 (3.17%)  2 6/123 (4.88%)  6
GGT increased  0/59 (0.00%)  0 2/63 (3.17%)  2 2/57 (3.51%)  2 2/63 (3.17%)  2 2/123 (1.63%)  2
Haematemesis  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
haemoptysis  7/59 (11.86%)  10 3/63 (4.76%)  3 4/57 (7.02%)  4 5/63 (7.94%)  5 7/123 (5.69%)  10
Lymphadenopathy  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 2/123 (1.63%)  2
Neutropenia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 2/123 (1.63%)  2
Neutrophilia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Normochromic normocytic anaemia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Thrombocytopenia  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Cardiac disorders           
Atrial Flutter  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Atrioventricular block first degree  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 2/123 (1.63%)  2
Atrioventricular block second degree  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Bundle branch block right  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Electrocardiogram QT prolonged  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 5/63 (7.94%)  6 0/123 (0.00%)  0
heart rate increased  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Palpitations  1/59 (1.69%)  1 0/63 (0.00%)  0 1/57 (1.75%)  1 3/63 (4.76%)  3 1/123 (0.81%)  1
Sinus tachycardia  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Tachycardia  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  2 1/63 (1.59%)  1 1/123 (0.81%)  1
Ventricular extrasystoles  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Ear and labyrinth disorders           
Ear pruritus  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Endocrine disorders           
hyperglycaemia  1/59 (1.69%)  1 2/63 (3.17%)  2 0/57 (0.00%)  0 1/63 (1.59%)  2 1/123 (0.81%)  2
Eye disorders           
Conjunctival discolouration  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Conjunctivitis  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Dry eye  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Eye irrritation  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Myopia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Vision blurred  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Visual acuity reduced  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 1/123 (0.81%)  1
Visual acuity reduced transiently  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Gastrointestinal disorders           
Abdominal pain  3/59 (5.08%)  3 1/63 (1.59%)  1 2/57 (3.51%)  2 2/63 (3.17%)  2 1/123 (0.81%)  1
Abdominal pain upper  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Constipation  2/59 (3.39%)  2 2/63 (3.17%)  3 0/57 (0.00%)  0 2/63 (3.17%)  2 0/123 (0.00%)  0
Diarrhoea  4/59 (6.78%)  5 2/63 (3.17%)  2 2/57 (3.51%)  2 5/63 (7.94%)  5 4/123 (3.25%)  4
duodenitis  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Dyspepsia  1/59 (1.69%)  1 1/63 (1.59%)  1 1/57 (1.75%)  1 1/63 (1.59%)  1 1/123 (0.81%)  1
Gastritis  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 2/63 (3.17%)  2 1/123 (0.81%)  1
gastroentertitis bacterial  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Nausea  7/59 (11.86%)  7 9/63 (14.29%)  9 8/57 (14.04%)  8 7/63 (11.11%)  9 7/123 (5.69%)  7
Oral discomfort  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Peptic ulcer  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Post-tussive vomiting  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  3 0/63 (0.00%)  0 1/123 (0.81%)  1
Salivary gland enlargement  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Tongue ulceration  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Toothache  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 1/63 (1.59%)  1 3/123 (2.44%)  3
Vomiting  5/59 (8.47%)  6 11/63 (17.46%)  11 8/57 (14.04%)  8 8/63 (12.70%)  9 15/123 (12.20%)  16
General disorders           
Asthenia  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Dental caries  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Fatigue  1/59 (1.69%)  1 1/63 (1.59%)  1 1/57 (1.75%)  1 1/63 (1.59%)  1 1/123 (0.81%)  1
feeling cold  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Generalized oedema  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
haemarrhoids  1/59 (1.69%)  1 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
headache  6/59 (10.17%)  8 5/63 (7.94%)  5 4/57 (7.02%)  4 4/63 (6.35%)  6 11/123 (8.94%)  11
Hordeolum  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
hypercholsterolaemia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Mass  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Night sweats  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Oedema peripheral  1/59 (1.69%)  1 0/63 (0.00%)  0 2/57 (3.51%)  2 1/63 (1.59%)  1 0/123 (0.00%)  0
Pain in face  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Pyrexia  2/59 (3.39%)  3 3/63 (4.76%)  3 3/57 (5.26%)  3 2/63 (3.17%)  3 5/123 (4.07%)  5
Suprapubic pain  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Tenderness  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Hepatobiliary disorders           
Alcoholic liver disease  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
drug induced liver injury  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
hepatic enzyme increased  0/59 (0.00%)  0 1/63 (1.59%)  1 1/57 (1.75%)  1 1/63 (1.59%)  1 2/123 (1.63%)  2
hepatotoxicity  0/59 (0.00%)  0 1/63 (1.59%)  1 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
hyperbilirubinaemia  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Jaundice  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Jaundice cholestatic  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Liver injury  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Immune system disorders           
Conjunctivitis allergic  1/59 (1.69%)  3 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Drug eruption  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Drug hypersensitivity  0/59 (0.00%)  0 1/63 (1.59%)  1 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
goitre  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Hypersensitivity  0/59 (0.00%)  0 2/63 (3.17%)  2 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Rhinitis seasonal  1/59 (1.69%)  2 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Seasonal allergy  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 2/123 (1.63%)  2
Infections and infestations           
Abcess of eyelid  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Acarodermatitis  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Body tinea  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 2/63 (3.17%)  2 0/123 (0.00%)  0
Influenza  5/59 (8.47%)  5 4/63 (6.35%)  4 1/57 (1.75%)  1 4/63 (6.35%)  4 7/123 (5.69%)  7
Lower respiratory tract infection  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Malaria  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Nasopharyngitis  1/59 (1.69%)  1 2/63 (3.17%)  2 1/57 (1.75%)  1 1/63 (1.59%)  3 4/123 (3.25%)  4
Otitis media  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Pericarditis tuberculous  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Pneumonia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Pneumonia bacterial  0/59 (0.00%)  0 1/63 (1.59%)  1 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Rash pustular  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Respiratory tract infection  2/59 (3.39%)  2 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Rhinitis  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Sinusitis  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Subcutaneous abscess  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Superinfection bacterial  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Tinea capitis  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Tinea infection  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Upper respiratory tract infection  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 1/123 (0.81%)  1
Urinary tract infection  2/59 (3.39%)  3 0/63 (0.00%)  0 0/57 (0.00%)  0 2/63 (3.17%)  2 4/123 (3.25%)  6
Urogenital infection bacterial  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Vulvovaginal candidiasis  2/59 (3.39%)  2 0/63 (0.00%)  0 0/57 (0.00%)  0 4/63 (6.35%)  4 2/123 (1.63%)  3
Vulvovaginal mycotic infection  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Injury, poisoning and procedural complications           
Accidental overdose  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Arthropod bite  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Contusion  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Injury  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Joint injury  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Laceration  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Muscle strain  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 1/123 (0.81%)  1
Open wound  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Periorbital haematoma  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Post-traumatic neck syndrome  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Investigations           
Activated partial thromboplastin time prolonged  1/59 (1.69%)  1 0/63 (0.00%)  0 1/57 (1.75%)  1 1/63 (1.59%)  1 1/123 (0.81%)  1
Alanine aminotransferase increased  2/59 (3.39%)  2 1/63 (1.59%)  1 1/57 (1.75%)  2 2/63 (3.17%)  2 2/123 (1.63%)  2
Aspartate aminotransferase increased  2/59 (3.39%)  2 2/63 (3.17%)  2 1/57 (1.75%)  1 4/63 (6.35%)  4 3/123 (2.44%)  3
Bilirubin conjugated increased  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Blood albumine decreased  1/59 (1.69%)  1 2/63 (3.17%)  2 2/57 (3.51%)  2 0/63 (0.00%)  0 2/123 (1.63%)  2
Blood alkaline phosphatase increased  0/59 (0.00%)  0 2/63 (3.17%)  2 2/57 (3.51%)  2 3/63 (4.76%)  3 0/123 (0.00%)  0
Blood bilirubin increased  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Blood potassium increased  0/59 (0.00%)  0 0/63 (0.00%)  0 3/57 (5.26%)  3 0/63 (0.00%)  0 0/123 (0.00%)  0
Blood pressure increased  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 2/123 (1.63%)  2
Breath sounds abnormal  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
International normalised ratio increased  1/59 (1.69%)  1 1/63 (1.59%)  1 1/57 (1.75%)  1 1/63 (1.59%)  1 3/123 (2.44%)  3
Lipase  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Lipase decreased  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Lipase increased  2/59 (3.39%)  2 4/63 (6.35%)  4 4/57 (7.02%)  5 2/63 (3.17%)  2 2/123 (1.63%)  2
Pregnancy test false positive  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Protein urine present  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Serum ferritin increased  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Transaminases increased  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  2
White blood cell count decreased  0/59 (0.00%)  0 2/63 (3.17%)  2 0/57 (0.00%)  0 0/63 (0.00%)  0 2/123 (1.63%)  2
Metabolism and nutrition disorders           
Decreased appetite  3/59 (5.08%)  3 1/63 (1.59%)  1 3/57 (5.26%)  3 2/63 (3.17%)  2 6/123 (4.88%)  7
Hyperkalaemia  1/59 (1.69%)  1 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Hyperlipidaemia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  2
Hypernatraemia  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Hypoalbuminaemia  1/59 (1.69%)  1 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Hypokalaemia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Hyponatraemia  2/59 (3.39%)  2 3/63 (4.76%)  3 1/57 (1.75%)  1 1/63 (1.59%)  1 4/123 (3.25%)  4
Type 2 diabetes mellitus  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthralgia  7/59 (11.86%)  8 8/63 (12.70%)  8 6/57 (10.53%)  7 10/63 (15.87%)  10 18/123 (14.63%)  19
Back pain  3/59 (5.08%)  3 0/63 (0.00%)  0 2/57 (3.51%)  2 1/63 (1.59%)  1 3/123 (2.44%)  3
Costochondritis  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Dactylitis  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Joint effusion  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Joint stiffness  0/59 (0.00%)  0 1/63 (1.59%)  2 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Joint swelling  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 2/63 (3.17%)  2 1/123 (0.81%)  1
Muscle spasms  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Muscular weakness  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Musculoskeletal chest pain  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 2/123 (1.63%)  2
Musculoskeletal pain  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Myalgia  1/59 (1.69%)  1 2/63 (3.17%)  3 4/57 (7.02%)  4 2/63 (3.17%)  2 2/123 (1.63%)  2
Neck pain  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Pain in extremity  3/59 (5.08%)  3 3/63 (4.76%)  3 0/57 (0.00%)  0 1/63 (1.59%)  1 2/123 (1.63%)  2
Polyarthritis  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Nervous system disorders           
Ageusia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Hypoaesthesia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Memory impairment  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Neuropathy peripheral  0/59 (0.00%)  0 5/63 (7.94%)  5 0/57 (0.00%)  0 2/63 (3.17%)  2 4/123 (3.25%)  4
Optic neuritis  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Paraesthesia  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 1/123 (0.81%)  1
Syncope  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Tension headache  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  2 0/63 (0.00%)  0 0/123 (0.00%)  0
Pregnancy, puerperium and perinatal conditions           
Pregnancy  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 1/123 (0.81%)  1
Psychiatric disorders           
Insomnia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Renal and urinary disorders           
Dysuria  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Urinary tract obstruction  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Reproductive system and breast disorders           
Amenorrhoea  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Breast pain  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Breast tenderness  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Dysfunctional uterine bleeding  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Menorrhagia  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 2/63 (3.17%)  2 1/123 (0.81%)  1
Vaginal haemorrhage  2/59 (3.39%)  4 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Vulvovaginal pruritus  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Respiratory, thoracic and mediastinal disorders           
Asthma  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Chest discomfort  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Chest pain  6/59 (10.17%)  6 4/63 (6.35%)  5 4/57 (7.02%)  4 2/63 (3.17%)  2 6/123 (4.88%)  6
Cough  2/59 (3.39%)  2 0/63 (0.00%)  0 0/57 (0.00%)  0 2/63 (3.17%)  3 2/123 (1.63%)  2
Dyspnoea  0/59 (0.00%)  0 1/63 (1.59%)  1 2/57 (3.51%)  3 1/63 (1.59%)  2 1/123 (0.81%)  1
Nasal congestion  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Pleural effusion  0/59 (0.00%)  0 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Pleuritic pain  1/59 (1.69%)  1 1/63 (1.59%)  1 0/57 (0.00%)  0 1/63 (1.59%)  1 1/123 (0.81%)  1
Productive cough  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
Respiratory distress  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Rhinorrhoea  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 2/123 (1.63%)  3
Rhonchi  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Skin and subcutaneous tissue disorders           
Acne  1/59 (1.69%)  1 3/63 (4.76%)  3 0/57 (0.00%)  0 3/63 (4.76%)  3 6/123 (4.88%)  6
Alopecia  1/59 (1.69%)  1 1/63 (1.59%)  1 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Dermatitis  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 1/123 (0.81%)  1
Excema  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
fungal skin infection  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
herpes simplex  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 1/123 (0.81%)  1
herplex zoster  1/59 (1.69%)  1 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  0 0/123 (0.00%)  0
Pruritus  6/59 (10.17%)  6 11/63 (17.46%)  14 5/57 (8.77%)  6 9/63 (14.29%)  9 17/123 (13.82%)  18
Pruritus generalised  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Rash  5/59 (8.47%)  5 5/63 (7.94%)  5 6/57 (10.53%)  6 5/63 (7.94%)  5 5/123 (4.07%)  5
Rash maculo-papular  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 0/63 (0.00%)  3/123 (2.44%)  4
Rash papular  1/59 (1.69%)  1 3/63 (4.76%)  3 0/57 (0.00%)  0 1/63 (1.59%)  1 2/123 (1.63%)  3
Rash pruritic  2/59 (3.39%)  3 2/63 (3.17%)  2 1/57 (1.75%)  1 2/63 (3.17%)  2 3/123 (2.44%)  3
Xeroderma  0/59 (0.00%)  0 0/63 (0.00%)  0 0/57 (0.00%)  0 1/63 (1.59%)  1 0/123 (0.00%)  0
Vascular disorders           
Hypertension  1/59 (1.69%)  1 1/63 (1.59%)  1 1/57 (1.75%)  1 1/63 (1.59%)  1 3/123 (2.44%)  3
Post thrombotic syndrome  0/59 (0.00%)  0 0/63 (0.00%)  0 1/57 (1.75%)  1 0/63 (0.00%)  0 0/123 (0.00%)  0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Norbert Heinrich
Organization: Tropical Institute of the Ludwig-Maximilians University in Munich, Germany
Phone: 0049 89 2180 17605
EMail: heinrich@lrz.uni-muenchen.de
Layout table for additonal information
Responsible Party: Michael Hoelscher, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT01785186    
Other Study ID Numbers: PanACEA-MAMS-TB-01
First Submitted: December 17, 2012
First Posted: February 7, 2013
Results First Submitted: August 22, 2017
Results First Posted: September 20, 2017
Last Update Posted: September 20, 2017