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Trial record 63 of 76 for:    "Bacterial Infectious Disease" | "Polyestradiol phosphate"

Shortening Treatment by Advancing Novel Drugs (STAND)

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ClinicalTrials.gov Identifier: NCT02342886
Recruitment Status : Completed
First Posted : January 21, 2015
Results First Posted : March 26, 2019
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Global Alliance for TB Drug Development

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Tuberculosis, Pulmonary, Drug Sensitive
Tuberculosis, Pulmonary, Multi Drug-resistant
Interventions Drug: Moxifloxacin
Drug: PA-824
Drug: Pyrazinamide
Drug: HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination)
Drug: HR (rifampicin plus isoniazid combination tablets)
Enrollment 284
Recruitment Details Adult male and female patients with drug-sensitive (DS) and multi-drug resistant (MDR) smear-positive pulmonary tuberculosis (TB) were recruited into this open-label multicenter study.
Pre-assignment Details Patients were confirmed sputum positive for tubercule bacilli on smear microscopy. DS-TB patients were required to be sensitive to rifampicin and newly diagnosed with pulmonary TB (or untreated for at least 3 years). MDR-TB patients were required to be resistant to rifampicin. Both DS and MDR-TB patients could be sensitive/resistant to isoniazid.
Arm/Group Title DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 2 Months HRZE / 4 Months HR MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide
Hide Arm/Group Description Patients with DS-TB were randomized to receive 400 milligrams (mg) moxifloxacin + 100 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 150 mg rifampicin + 75 mg isoniazid + 400 mg pyrazinamide + 275 mg ethambutol combination tablets (HRZE) orally once daily from Weeks 1 to 8 during the treatment period. Patients then received 150 mg rifiampicin + 75 mg isoniazid combination tablets (HR) orally once daily from Weeks 9 to 26 during the treatment period. The daily dose of HRZE and HR was calculated based on patients' weight. Patients then entered a follow-up period up to Month 24. Patients with MDR-TB received 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24.
Period Title: Overall Study
Started 65 71 67 68 13
Completed Month 12 Follow-Up 43 52 49 57 10
Completed Month 24 Follow-Up 40 47 46 53 10
Completed [1] 57 63 52 59 10
Not Completed 8 8 15 9 3
Reason Not Completed
Treatment non-compliance             1             0             0             1             0
Late exclusion: rifampicin resistance             1             0             0             0             0
Adverse event/specific toxicity             4             3             11             2             1
Lost to Follow-up             1             0             0             0             0
Death             1             2             1             0             1
Withdrawal by Subject             0             1             0             1             0
Investigator/sponsor decision             0             2             0             3             1
Pregnancy             0             0             2             0             0
Late exclusion: pyrazinamide resistance             0             0             1             0             0
Protocol Violation             0             0             0             2             0
[1]
Completed Treatment
Arm/Group Title DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 2 Months HRZE / 4 Months HR MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide Total
Hide Arm/Group Description Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 100 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 150 mg rifampicin + 75 mg isoniazid + 400 mg pyrazinamide + 275 mg ethambutol combination tablets (HRZE) orally once daily from Weeks 1 to 8 during the treatment period. Patients then received 150 mg rifiampicin + 75 mg isoniazid combination tablets (HR) orally once daily from Weeks 9 to 26 during the treatment period. The daily dose of HRZE and HR was calculated based on patients' weight. Patients then entered a follow-up period up to Month 24. Patients with MDR-TB received 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24. Total of all reporting groups
Overall Number of Baseline Participants 65 71 67 68 13 284
Hide Baseline Analysis Population Description
The Safety analysis population included all patients who were randomized (for the DS-TB patients) or assigned (for the MDR-TB patients) to trial medication and who received at least 1 dose of trial medication. Patients were classified according to treatment received.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 71 participants 67 participants 68 participants 13 participants 284 participants
<=18 years
2
   3.1%
2
   2.8%
2
   3.0%
0
   0.0%
0
   0.0%
6
   2.1%
Between 18 and 65 years
63
  96.9%
67
  94.4%
65
  97.0%
67
  98.5%
13
 100.0%
275
  96.8%
>=65 years
0
   0.0%
2
   2.8%
0
   0.0%
1
   1.5%
0
   0.0%
3
   1.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 71 participants 67 participants 68 participants 13 participants 284 participants
Female
14
  21.5%
23
  32.4%
23
  34.3%
20
  29.4%
7
  53.8%
87
  30.6%
Male
51
  78.5%
48
  67.6%
44
  65.7%
48
  70.6%
6
  46.2%
197
  69.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 71 participants 67 participants 68 participants 13 participants 284 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
65
 100.0%
71
 100.0%
67
 100.0%
68
 100.0%
13
 100.0%
284
 100.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 71 participants 67 participants 68 participants 13 participants 284 participants
Asian
3
   4.6%
6
   8.5%
6
   9.0%
4
   5.9%
0
   0.0%
19
   6.7%
Black or African American
45
  69.2%
49
  69.0%
45
  67.2%
44
  64.7%
8
  61.5%
191
  67.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.5%
0
   0.0%
1
   0.4%
White
3
   4.6%
3
   4.2%
3
   4.5%
3
   4.4%
2
  15.4%
14
   4.9%
Mixed Race
8
  12.3%
12
  16.9%
8
  11.9%
13
  19.1%
3
  23.1%
44
  15.5%
Other
6
   9.2%
1
   1.4%
5
   7.5%
3
   4.4%
0
   0.0%
15
   5.3%
1.Primary Outcome
Title Incidence of Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Modified Intent to Treat [MITT] Population)
Hide Description

Patients were classified as having a favorable, unfavorable or unassessable status at 12 months from the start of therapy.

A favourable status was a negative culture status at 12 months from start of therapy in patients who had not already been classified as having an unfavorable outcome, and whose last positive culture result was followed by at least 2 negative culture results. Patients with an unfavorable status did not achieve/maintain culture negative status, or previously had culture negative status who following end of treatment (EOT), had 2 positive cultures, or had a positive culture not followed by 2 negative cultures, or were dying from any cause during treatment (except accidental cause not including suicide), or were dying from TB related causes during follow-up, or required an extension, restart or change of treatment except for reinfection/pregnancy, or failed to complete adequate treatment who were unassessable at 12 months or lost to follow-up/withdrawn before EOT.

Time Frame From Day 1 to Month 12.
Hide Outcome Measure Data
Hide Analysis Population Description
The MITT population included all randomized patients excluding late screening failures, lost to follow-up/withdrawn patients who were culture negative, pregnancy, accidental death during treatment, death during follow-up without TB relapse evidence, re-infection with new TB strain + missing/contaminated Month 12 sputum sample.
Arm/Group Title DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 2 Months HRZE / 4 Months HR MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide
Hide Arm/Group Description:
Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 100 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24.
Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24.
Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24.
Patients with DS-TB were randomized to receive 150 mg rifampicin + 75 mg isoniazid + 400 mg pyrazinamide + 275 mg ethambutol combination tablets (HRZE) orally once daily from Weeks 1 to 8 during the treatment period. Patients then received 150 mg rifiampicin + 75 mg isoniazid combination tablets (HR) orally once daily from Weeks 9 to 26 during the treatment period. The daily dose of HRZE and HR was calculated based on patients' weight. Patients then entered a follow-up period up to Month 24.

Patients with MDR-TB received 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24.

Note: The MDR-TB group was not randomized and not included in the analysis population.

Overall Number of Participants Analyzed 57 61 56 60 11
Measure Type: Count of Participants
Unit of Measure: Participants
Favorable
38
  66.7%
46
  75.4%
43
  76.8%
52
  86.7%
10
  90.9%
Unfavorable
19
  33.3%
15
  24.6%
13
  23.2%
8
  13.3%
1
   9.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide, DS-TB: 2 Months HRZE / 4 Months HR
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was assessed using the upper bound of the two-sided 95% confidence interval (CI) for the difference between the percentage of patients who are classified as having an unfavourable status on the intervention (6 months moxifloxacin + 200 mg PA-824 + pyrazinamide) and the control regimen (2 months HRZE/ 4 months HR). The intervention was considered to be non-inferior to the control arm if the upper bound 95% CI was < 12%.
Method of Estimation Estimation Parameter Treatment difference: unfavourable rate
Estimated Value 9.88
Confidence Interval (2-Sided) 95%
-4.13 to 23.89
Estimation Comments (DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide) - (DS-TB: 2 Months HRZE/ 4 Months HR).
2.Primary Outcome
Title Incidence of Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Per Protocol [PP] Population)
Hide Description

Patients were classified as having a favorable, unfavorable or unassessable status at 12 months from the start of therapy.

A favourable status was a negative culture status at 12 months from start of therapy in patients who had not already been classified as having an unfavorable outcome, and whose last positive culture result was followed by at least 2 negative culture results. Patients with an unfavorable status did not achieve/maintain culture negative status, or previously had culture negative status who following EOT, had 2 positive cultures, or had a positive culture not followed by 2 negative cultures, or died from any cause during treatment (except accidental cause not including suicide), or were dying from TB related causes during follow-up, or required a restart or change of treatment because of an unfavorable outcome with or without bacteriological confirmation, ie, on bacteriological, radiographic or clinical grounds.

Time Frame From Day 1 to Month 12.
Hide Outcome Measure Data
Hide Analysis Population Description
The PP population consisted of the MITT population, excluding patients who were lost to follow-up/withdrawn, had modified/extended treatment for reasons other than unfavourable therapeutic response, did not receive adequate amount of allocated study regimen and patients with major protocol deviations, unless already classified as unfavourable.
Arm/Group Title DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 2 Months HRZE / 4 Months HR MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide
Hide Arm/Group Description:
Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 100 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24.
Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24.
Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24.
Patients with DS-TB were randomized to receive 150 mg rifampicin + 75 mg isoniazid + 400 mg pyrazinamide + 275 mg ethambutol combination tablets (HRZE) orally once daily from Weeks 1 to 8 during the treatment period. Patients then received 150 mg rifiampicin + 75 mg isoniazid combination tablets (HR) orally once daily from Weeks 9 to 26 during the treatment period. The daily dose of HRZE and HR was calculated based on patients' weight. Patients then entered a follow-up period up to Month 24.

Patients with MDR-TB received 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24.

Note: The MDR-TB group was not randomized and not included in the analysis population.

Overall Number of Participants Analyzed 52 57 47 53 10
Measure Type: Count of Participants
Unit of Measure: Participants
Favorable
38
  73.1%
46
  80.7%
43
  91.5%
52
  98.1%
10
 100.0%
Unfavorable
14
  26.9%
11
  19.3%
4
   8.5%
1
   1.9%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide, DS-TB: 2 Months HRZE / 4 Months HR
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was assessed using the upper bound of the two-sided 95% CI for the difference between the percentage of patients who are classified as having an unfavourable status on the intervention (6 months moxifloxacin + 200 mg PA-824 + pyrazinamide) and the control regimen (2 months HRZE/ 4 months HR). The intervention was considered to be non-inferior to the control arm if the upper bound 95% CI was < 12%.
Method of Estimation Estimation Parameter Treatment difference: unfavourable rate
Estimated Value 6.62
Confidence Interval (2-Sided) 95%
-2.15 to 15.40
Estimation Comments (DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide) - (DS-TB: 2 Months HRZE/ 4 Months HR).
Time Frame Treatment emergent adverse events were collected from Day 1 up to and including 14 days after the last administration of trial medication (up to a maximum of 28 weeks).
Adverse Event Reporting Description The Safety analysis population included all patients in the randomized/assigned to trial medication population set who received at least 1 dose of trial medication. Patients were classified according to treatment received.
 
Arm/Group Title DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 2 Months HRZE/ 4 Months HR MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide
Hide Arm/Group Description Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 100 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 4 months during the treatment period (from Day 1 to Week 17). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24. Patients with DS-TB were randomized to receive 150 mg rifampicin + 75 mg isoniazid + 400 mg pyrazinamide + 275 mg ethambutol combination tablets (HRZE) orally once daily from Weeks 1 to 8 during the treatment period. Patients then received 150 mg rifiampicin + 75 mg isoniazid combination tablets (HR) orally once daily from Weeks 9 to 26 during the treatment period. The daily dose of HRZE and HR was calculated based on patients' weight. Patients then entered a follow-up period up to Month 24. Patients with MDR-TB received 400 mg moxifloxacin + 200 mg pretomanid (PA-824) + 1500 mg pyrazinamide orally once daily for 6 months during the treatment period (from Day 1 to Week 26). Patients then entered a follow-up period up to Month 24.
All-Cause Mortality
DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 2 Months HRZE/ 4 Months HR MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/65 (6.15%)   3/71 (4.23%)   3/67 (4.48%)   2/68 (2.94%)   1/13 (7.69%) 
Show Serious Adverse Events Hide Serious Adverse Events
DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 2 Months HRZE/ 4 Months HR MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/65 (4.62%)   8/71 (11.27%)   8/67 (11.94%)   3/68 (4.41%)   3/13 (23.08%) 
Cardiac disorders           
Cardiac ventricular thrombosis  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Left ventricular dysfunction  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Myocarditis  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Gastrointestinal disorders           
Vomiting  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
General disorders           
Death  1  0/65 (0.00%)  0/71 (0.00%)  1/67 (1.49%)  0/68 (0.00%)  0/13 (0.00%) 
Hepatobiliary disorders           
Acute hepatic failure  1  1/65 (1.54%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Hepatotoxicity  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Jaundice  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Immune system disorders           
Hypersensitivity  1  1/65 (1.54%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Infections and infestations           
Aspergillus infection  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Lymph node Tuberculosis  1  1/65 (1.54%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Nasal candidiasis  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Pneumonia  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Pulmonary Tuberculosis  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  1/68 (1.47%)  0/13 (0.00%) 
Urinary tract infection  1  0/65 (0.00%)  0/71 (0.00%)  1/67 (1.49%)  0/68 (0.00%)  0/13 (0.00%) 
Injury, poisoning and procedural complications           
Soft tissue injury  1  0/65 (0.00%)  0/71 (0.00%)  1/67 (1.49%)  0/68 (0.00%)  0/13 (0.00%) 
Intentional overdose  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  1/68 (1.47%)  0/13 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  0/65 (0.00%)  1/71 (1.41%)  4/67 (5.97%)  0/68 (0.00%)  0/13 (0.00%) 
Aspartate aminotransferase increased  1  0/65 (0.00%)  2/71 (2.82%)  3/67 (4.48%)  0/68 (0.00%)  0/13 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Anal squamous cell carcinoma  1  0/65 (0.00%)  0/71 (0.00%)  1/67 (1.49%)  0/68 (0.00%)  0/13 (0.00%) 
Lung cancer metastatic  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Nervous system disorders           
Hepatic encephalopathy  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Seizure  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  1/68 (1.47%)  0/13 (0.00%) 
Renal and urinary disorders           
Bladder mass  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  0/13 (0.00%) 
Reproductive system and breast disorders           
Acquired hydrocele  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  1/68 (1.47%)  0/13 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Pneumothorax  1  0/65 (0.00%)  0/71 (0.00%)  1/67 (1.49%)  0/68 (0.00%)  0/13 (0.00%) 
Pneumothorax spontaneous  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Pulmonary oedema  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
1
Term from vocabulary, MedDRA v 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide DS-TB: 2 Months HRZE/ 4 Months HR MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   61/65 (93.85%)   62/71 (87.32%)   63/67 (94.03%)   62/68 (91.18%)   12/13 (92.31%) 
Blood and lymphatic system disorders           
Anaemia  1  1/65 (1.54%)  1/71 (1.41%)  4/67 (5.97%)  5/68 (7.35%)  0/13 (0.00%) 
Lymphadenopathy  1  0/65 (0.00%)  1/71 (1.41%)  1/67 (1.49%)  1/68 (1.47%)  1/13 (7.69%) 
Cardiac disorders           
Atrial fibrillation  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Ear and labyrinth disorders           
Deafness unilateral  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Eye disorders           
Visual acuity reduced  1  0/65 (0.00%)  0/71 (0.00%)  4/67 (5.97%)  8/68 (11.76%)  0/13 (0.00%) 
Eye pain  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Eyelid haematoma  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Gastrointestinal disorders           
Nausea  1  13/65 (20.00%)  11/71 (15.49%)  11/67 (16.42%)  3/68 (4.41%)  2/13 (15.38%) 
Vomiting  1  13/65 (20.00%)  8/71 (11.27%)  6/67 (8.96%)  4/68 (5.88%)  2/13 (15.38%) 
Diarrhoea  1  14/65 (21.54%)  7/71 (9.86%)  5/67 (7.46%)  3/68 (4.41%)  1/13 (7.69%) 
Abdominal pain  1  3/65 (4.62%)  2/71 (2.82%)  5/67 (7.46%)  3/68 (4.41%)  2/13 (15.38%) 
Toothache  1  1/65 (1.54%)  2/71 (2.82%)  2/67 (2.99%)  1/68 (1.47%)  1/13 (7.69%) 
Infections and infestations           
Gastroenteritis  1  2/65 (3.08%)  2/71 (2.82%)  5/67 (7.46%)  2/68 (2.94%)  0/13 (0.00%) 
Upper respiratory tract infection  1  2/65 (3.08%)  2/71 (2.82%)  4/67 (5.97%)  1/68 (1.47%)  1/13 (7.69%) 
Lower respiratory tract infection  1  1/65 (1.54%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Rhinitis  1  1/65 (1.54%)  0/71 (0.00%)  1/67 (1.49%)  5/68 (7.35%)  0/13 (0.00%) 
Fungal skin infection  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  1/68 (1.47%)  1/13 (7.69%) 
Furuncle  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  1/68 (1.47%)  1/13 (7.69%) 
Injury, poisoning and procedural complications           
Skin abrasion  1  0/65 (0.00%)  0/71 (0.00%)  1/67 (1.49%)  0/68 (0.00%)  1/13 (7.69%) 
Investigations           
Aspartate aminotransferase increased  1  15/65 (23.08%)  10/71 (14.08%)  15/67 (22.39%)  17/68 (25.00%)  1/13 (7.69%) 
Alanine aminotransferase increased  1  13/65 (20.00%)  10/71 (14.08%)  14/67 (20.90%)  11/68 (16.18%)  1/13 (7.69%) 
Blood uric acid increased  1  15/65 (23.08%)  11/71 (15.49%)  12/67 (17.91%)  8/68 (11.76%)  1/13 (7.69%) 
Gamma-glutamyltransferase increased  1  8/65 (12.31%)  11/71 (15.49%)  11/67 (16.42%)  12/68 (17.65%)  0/13 (0.00%) 
Blood glucose increased  1  5/65 (7.69%)  2/71 (2.82%)  2/67 (2.99%)  4/68 (5.88%)  0/13 (0.00%) 
Blood alkaline phosphatase increased  1  4/65 (6.15%)  1/71 (1.41%)  3/67 (4.48%)  3/68 (4.41%)  0/13 (0.00%) 
Protein urine present  1  2/65 (3.08%)  1/71 (1.41%)  2/67 (2.99%)  2/68 (2.94%)  1/13 (7.69%) 
Blood urine present  1  0/65 (0.00%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Metabolism and nutrition disorders           
Hyperuricaemia  1  20/65 (30.77%)  21/71 (29.58%)  14/67 (20.90%)  22/68 (32.35%)  2/13 (15.38%) 
Decreased appetite  1  4/65 (6.15%)  2/71 (2.82%)  2/67 (2.99%)  2/68 (2.94%)  0/13 (0.00%) 
Hyperglycaemia  1  2/65 (3.08%)  1/71 (1.41%)  5/67 (7.46%)  0/68 (0.00%)  0/13 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  15/65 (23.08%)  24/71 (33.80%)  19/67 (28.36%)  15/68 (22.06%)  4/13 (30.77%) 
Myalgia  1  3/65 (4.62%)  7/71 (9.86%)  1/67 (1.49%)  5/68 (7.35%)  1/13 (7.69%) 
Pain in extremity  1  2/65 (3.08%)  1/71 (1.41%)  2/67 (2.99%)  3/68 (4.41%)  1/13 (7.69%) 
Musculoskeletal pain  1  0/65 (0.00%)  1/71 (1.41%)  1/67 (1.49%)  2/68 (2.94%)  1/13 (7.69%) 
Flank pain  1  1/65 (1.54%)  0/71 (0.00%)  0/67 (0.00%)  1/68 (1.47%)  1/13 (7.69%) 
Nervous system disorders           
Headache  1  5/65 (7.69%)  6/71 (8.45%)  7/67 (10.45%)  5/68 (7.35%)  2/13 (15.38%) 
Dizziness  1  3/65 (4.62%)  4/71 (5.63%)  7/67 (10.45%)  4/68 (5.88%)  2/13 (15.38%) 
Neuropathy peripheral  1  1/65 (1.54%)  0/71 (0.00%)  2/67 (2.99%)  4/68 (5.88%)  3/13 (23.08%) 
Somnolence  1  4/65 (6.15%)  0/71 (0.00%)  1/67 (1.49%)  2/68 (2.94%)  0/13 (0.00%) 
Burning sensation  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Renal and urinary disorders           
Haematuria  1  6/65 (9.23%)  3/71 (4.23%)  3/67 (4.48%)  5/68 (7.35%)  1/13 (7.69%) 
Proteinuria  1  6/65 (9.23%)  1/71 (1.41%)  3/67 (4.48%)  4/68 (5.88%)  0/13 (0.00%) 
Reproductive system and breast disorders           
Menometrorrhagia  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Respiratory, thoracic and mediastinal disorders           
Haemoptysis  1  6/65 (9.23%)  8/71 (11.27%)  5/67 (7.46%)  3/68 (4.41%)  2/13 (15.38%) 
Pleuritic pain  1  5/65 (7.69%)  4/71 (5.63%)  4/67 (5.97%)  2/68 (2.94%)  4/13 (30.77%) 
Pulmonary embolism  1  0/65 (0.00%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  2/13 (15.38%) 
Pneumothorax  1  0/65 (0.00%)  0/71 (0.00%)  1/67 (1.49%)  0/68 (0.00%)  1/13 (7.69%) 
Skin and subcutaneous tissue disorders           
Pruritus generalised  1  2/65 (3.08%)  2/71 (2.82%)  8/67 (11.94%)  11/68 (16.18%)  0/13 (0.00%) 
Pruritus  1  3/65 (4.62%)  2/71 (2.82%)  3/67 (4.48%)  5/68 (7.35%)  2/13 (15.38%) 
Rash  1  4/65 (6.15%)  2/71 (2.82%)  1/67 (1.49%)  6/68 (8.82%)  1/13 (7.69%) 
Rash pruritic  1  1/65 (1.54%)  1/71 (1.41%)  4/67 (5.97%)  2/68 (2.94%)  1/13 (7.69%) 
Rash papular  1  1/65 (1.54%)  2/71 (2.82%)  1/67 (1.49%)  2/68 (2.94%)  1/13 (7.69%) 
Night sweats  1  1/65 (1.54%)  0/71 (0.00%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
Vascular disorders           
Hypotension  1  1/65 (1.54%)  1/71 (1.41%)  0/67 (0.00%)  0/68 (0.00%)  1/13 (7.69%) 
1
Term from vocabulary, MedDRA v 20.0
Indicates events were collected by systematic assessment
Following 3 deaths associated with hepatotoxicity, recruitment was suspended, followed by a partial clinical hold by the United States Food and Drug Association. The hold was removed but the Sponsor permanently stopped recruitment in December 2016.
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.
The Investigator or any Sub-Investigator shall submit any oral or written publication or abstract concerning this study to the Sponsor not less than thirty (30) days prior to submission to any journal, other publication or meeting for review and removal of confidential information.
Results Point of Contact
Name/Title: Leandra Lombard, Director, Clinical Operations
Organization: TB Alliance
Phone: +27 87 700 3900
Responsible Party: Global Alliance for TB Drug Development
ClinicalTrials.gov Identifier: NCT02342886     History of Changes
Other Study ID Numbers: NC-006-(M-PA-Z)
First Submitted: October 14, 2014
First Posted: January 21, 2015
Results First Submitted: February 2, 2019
Results First Posted: March 26, 2019
Last Update Posted: March 26, 2019