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Early Bactericidal Activity of Linezolid, Gatifloxacin, Levofloxacin, Isoniazid (INH) and Moxifloxacin in HIV Negative Adults With Initial Episodes of Sputum Smear-Positive Pulmonary Tuberculosis

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ClinicalTrials.gov Identifier: NCT00396084
Recruitment Status : Completed
First Posted : November 6, 2006
Results First Posted : June 25, 2009
Last Update Posted : November 8, 2018
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Tuberculosis
Interventions Drug: Gatifloxacin
Drug: Isoniazid
Drug: Levofloxacin
Drug: Linezolid
Drug: Moxifloxacin
Enrollment 70

Recruitment Details Screening for the trial began in February 2004 in Vitória, Brazil. Non-HIV infected adults aged 18-65 years with suspected pulmonary tuberculosis (TB) were recruited at local TB posts and the Hospital Universitario Cassiano Antonio de Moraes of the Universidade Federal do Espírito Santo (UFES) in Vitória. Enrollment was completed in October 2007.
Pre-assignment Details A total of 113 adults with suspected pulmonary TB were evaluated for study participation. Forty-three were excluded because they did not meet the eligibility criteria, leaving a total of 70 patients.
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Linezolid 600 mg / Once Daily Linezolid 600 mg / Twice Daily Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description Gatifloxacin 400 mg/day x 7 days Levofloxacin 1000 mg/day x 7days Linezolid 600 mg/once daily x 7days Linezolid 600 mg twice daily x 7 days Moxifloxacin 400 mg/day x 7 days Isoniazid (INH) 300 mg/day x 7 days
Period Title: Overall Study
Started 10 10 10 10 10 20
Completed 10 10 10 9 9 18
Not Completed 0 0 0 1 1 2
Reason Not Completed
Adverse Event             0             0             0             0             1             2
Withdrawal by Subject             0             0             0             1             0             0
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Linezolid 600 mg / Once Daily Linezolid 600 mg / Twice Daily Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day Total
Hide Arm/Group Description Gatifloxacin 400 mg/day x 7 days Levofloxacin 1000 mg/day x 7days Linezolid 600 mg/once daily x 7days Linezolid 600 mg twice daily x 7 days Moxifloxacin 400 mg/day x 7 days Isoniazid (INH) 300 mg/day x 7 days Total of all reporting groups
Overall Number of Baseline Participants 10 10 10 10 10 20 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 20 participants 70 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
20
 100.0%
70
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 20 participants 70 participants
34.5
(27.0 to 40.0)
43.5
(42.0 to 46.0)
33.5
(23.0 to 42.0)
45.0
(39.0 to 48.0)
35.0
(25.0 to 37.0)
33.0
(23.0 to 43.5)
35.0
(26.0 to 44.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 20 participants 70 participants
Female
1
  10.0%
2
  20.0%
2
  20.0%
2
  20.0%
1
  10.0%
3
  15.0%
11
  15.7%
Male
9
  90.0%
8
  80.0%
8
  80.0%
8
  80.0%
9
  90.0%
17
  85.0%
59
  84.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Brazil Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 20 participants 70 participants
10 10 10 10 10 20 70
1.Primary Outcome
Title Sputum Bacillary Loads: Adjusted Area Under the Curve (aAUC)
Hide Description The adjusted area under the curve (aAUC) for sputum colony forming units (cfu) for each day on treatment was calculated. The aAUC represents the percentage of the expected AUC given no change in log cfu in response to study drug administration.
Time Frame Study drug administration duration - 7 days monotherapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The aAUC was calculated for 10 subjects per treatment arm (n=40).
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description:
Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/day x 7days
Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/day x 7 days
Overall Number of Participants Analyzed 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: Percentage
Day 1 0.98  (0.03) 0.98  (0.03) 0.96  (0.04) 0.95  (0.03)
Day 2 0.96  (0.03) 0.95  (0.05) 0.94  (0.06) 0.90  (0.04)
Day 3 0.92  (0.05) 0.91  (0.07) 0.91  (0.08) 0.87  (0.04)
Day 4 0.89  (0.07) 0.88  (0.08) 0.89  (0.09) 0.84  (0.04)
Day 5 0.87  (0.08) 0.85  (0.09) 0.87  (0.10) 0.81  (0.05)
Day 6 0.85  (0.08) 0.83  (0.10) 0.85  (0.10) 0.80  (0.06)
Day 7 0.82  (0.09) 0.81  (0.10) 0.83  (0.10) 0.80  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Mean adjusted aAUC for all 4 treatment groups over the 7 days of study drug administration
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Day 1. Pooled sputum bacillary load data for patients in the 3 fluoroquinolones arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.041
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Day 2. Pooled sputum bacillary load data for patients in the 3 fluoroquinolones arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Day 3. Pooled sputum bacillary load data for patients in the 3 fluoroquinolones arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Day 4. Pooled sputum bacillary load data for patients in the 3 fluoroquinolones arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Day 5. Pooled sputum bacillary load data for patients in the 3 fluoroquinolones arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Day 6. Pooled sputum bacillary load data for patients in the 3 fluoroquinolones arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Day 7. Pooled sputum bacillary load data for patients in the 3 fluoroquinolones arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.354
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title Difference in Sputum Bacillary Loads: Early Bactericidal Activity (EBA) Days 0 to 2; Fluoroquinolones/Isoniazid (INH) Comparison
Hide Description Early bactericidal activity (EBA 0-2) was calculated as the rate of fall in sputum colony forming units (cfu) (expressed in log10 units) during the first 2 days of monotherapy.
Time Frame Day 0 to Day 2 Monotherapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Early bactericidal activity (EBA 0-2) was calculated for 10 subjects per treatment arm (n=40).
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description:
Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/day x 7days
Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/day x 7 days
Overall Number of Participants Analyzed 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: log10 cfu/ml/day
0.35  (0.27) 0.45  (0.35) 0.33  (0.39) 0.67  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Mean values of EBA Days 0 to 2 for the 4 treatment groups were compared.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Two way comparison of INH against gatifloxacin using a simultaneous non-parametric procedure.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Two way comparison of INH against moxifloxacin using a simultaneous non-parametric procedure.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levofloxacin 1000 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Two way comparison of INH against levofloxacin using a simultaneous non-parametric procedure.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Primary Outcome
Title Extended Early Bactericidal Activity (EBA) From Days 2 to 7; Fluoroquinolones/Isoniazid (INH) Comparison
Hide Description The rate of fall in sputum cfu between day 2 and day 7 of monotherapy was estimated by the slope of the linear regression obtained by fitting the 6 sputum cfu values corresponding to Days 2 through 7.
Time Frame Day 2 to Day 7 Monotherapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
A total of 38 patients were analyzed for Early Bactericidal Activity (EBA) Days 2-7. One patient in the moxifloxacin arm discontinued the study drug after 4 days. One patient in the INH arm discontinued the study drug after 6 days.
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description:
Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/day x 7days
Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/day x 7 days
Overall Number of Participants Analyzed 10 10 9 9
Mean (Standard Deviation)
Unit of Measure: log10 cfu/ml/day
0.17  (0.13) 0.18  (0.13) 0.17  (0.09) 0.08  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments Mean values of EBA Days 2 to 7 for the 4 treatment groups were compared.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments The rate of fall in sputum cfu for the 4 treatment groups between day 2 and day 7 of monotherapy was estimated by the slope of the linear regression obtained from fitting the 6 sputum cfu values corresponding to days 2 through 7.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Gatifloxacin 400 mg/Day, Levofloxacin 1000 mg/Day, Moxifloxacin 400 mg/Day, Isoniazid (INH) 300 mg/Day
Comments EBA Days 2-7 for patients in the 3 fluoroquinolone groups were pooled and compared to bactericidal activity of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Primary Outcome
Title Sputum Bacillary Loads: Adjusted Area Under the Curve (aAUC)
Hide Description The adjusted area under the curve (aAUC) for sputum colony forming unit (cfu) for each day on treatment was calculated for patients in the INH arm and those in the Linezolid once daily and Linezolid twice daily arms. The aAUC represents the percentage of the expected AUC given no change in log cfu in response to study drug administration.
Time Frame Study drug administration duration - 7 days monotherapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The aAUC was calculated for 29 patients. One patient in the linezolid twice daily arm withdrew after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Mean (Standard Deviation)
Unit of Measure: Percentage
Day 1 0.94  (0.06) 0.98  (0.04) 0.98  (0.04)
Day 2 0.89  (0.08) 0.97  (0.07) 0.96  (0.07)
Day 3 0.89  (0.03) 0.96  (0.07) 0.95  (0.08)
Day 4 0.85  (0.09) 0.96  (0.07) 0.94  (0.08)
Day 5 0.83  (0.10) 0.95  (0.07) 0.94  (0.08)
Day 6 0.81  (0.12) 0.95  (0.07) 0.93  (0.07)
Day 7 0.83  (0.07) 0.95  (0.07) 0.93  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Mean adjusted aAUC for all 3 treatment groups over the 7 days of study drug administration
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Day 1. Pooled sputum bacillary load data for patients in the linezolid arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Day 2. Pooled sputum bacillary load data for patients in the linezolid arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Day 3. Pooled sputum bacillary load data for patients in the linezolid arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Day 4. Pooled sputum bacillary load data for patients in the linezolid arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Day 5. Pooled sputum bacillary load data for patients in the linezolid arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Day 6. Pooled sputum bacillary load data for patients in the linezolid arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Day 7. Pooled sputum bacillary load data for patients in the linezolid arms were combined and compared to that of patients in the INH arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Primary Outcome
Title Difference in Sputum Bacillary Loads: Early Bactericidal Activity (EBA) Days 0 to 2; Linezolid Once Daily/Linezolid Twice Daily/Isoniazid (INH) Comparison
Hide Description Early bactericidal activity (EBA 0-2) was calculated as the rate of fall in sputum cfu (expressed in log10 units) during the first 2 days of monotherapy. Mean values for the 3 treatment groups were compared.
Time Frame Day 0 to Day 2 Monotherapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
EBA 0-2 comparisons across groups were done for 29 patients. One patient in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Mean (Standard Deviation)
Unit of Measure: log10 cfu/ml/day
0.67  (0.35) 0.18  (0.27) 0.26  (0.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Mean values of EBA Days 0 to 2 for the 3 treatments groups were compared.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily
Comments Two way comparison of INH against Linezolid once daily using a simultaneous non-parametric procedure.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Mean EBA 0-2 of INH was compared to pooled Linezolid once daily and Linezolid twice daily results.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Primary Outcome
Title Difference in Sputum Bacillary Loads: Extended Early Bactericidal Activity (EBA) From Days 2 to 7; Linezolid Once Daily/Linezolid Twice Daily/INH Comparison
Hide Description The rate of fall in sputum cfu between day 2 and day 7 of monotherapy was estimated by the slope of the linear regression obtained by fitting the 6 sputum cfu values corresponding to Days 2 through 7.
Time Frame Day 2 to Day 7 Monotherapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One patient in the INH arm discontinued the study drug after 5 days. Days 3 and 7 cultures for another patient in the INH arm were contaminated and cfu data are not available for this patient. One patient in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 8 10 9
Mean (Standard Deviation)
Unit of Measure: log10 cfu/ml
0.16  (0.11) 0.09  (0.17) 0.04  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments Mean values EBA Days 2-7 for the 3 treatment groups were compared.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments The rate of fall in sputum cfu for the 3 treatment groups between day 2 and day 7 of monotherapy was estimated by the slope of the linear regression obtained from fitting the 6 sputum cfu values corresponding to days 2 through 7.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isoniazid 300 mg/Day, Linezolid 600 mg/Once Daily, Linezolid 600 mg/Twice Daily
Comments EBA Days 2-7 for INH was compared to that of the pooled linezolid arms.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Sputum mRNA Clearance Rate - Results Are Pending.
Hide Description [Not Specified]
Time Frame Study drug administration duration
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Sputum Cytokine Proteins - Results Are Pending.
Hide Description [Not Specified]
Time Frame Study drug administration duration
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Maximum Plasma Drug Concentration (Cmax)
Hide Description Maximum plasma concentration, given sampling scheme
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. Plasma samples were collected at 7 time points on the 5th day after beginning study drug monotherapy. One subject in the moxifloxacin arm was discontinued from the study before day 5 and did not undergo PK sampling.
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description:
Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/day x 7days
Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/day x 7 days
Overall Number of Participants Analyzed 10 10 9 10
Median (Full Range)
Unit of Measure: ug/ml
4.8
(3.8 to 6.4)
15.6
(8.6 to 43.0)
6.1
(4.5 to 9.0)
3.6
(2.5 to 6.1)
10.Secondary Outcome
Title Time to Maximum Plasma Drug Concentration (Tmax) and Half-life
Hide Description [Not Specified]
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. One subject in the moxifloxacin arm was discontinued from the study before day 5 and did not undergo PK sampling.
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description:
Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/day x 7days
Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/day x 7 days
Overall Number of Participants Analyzed 10 10 9 10
Median (Full Range)
Unit of Measure: hours
Tmax
1.5
(1.0 to 8.0)
1.0
(1.0 to 4.0)
1.0
(1.0 to 2.0)
1
(1.0 to 2.0)
Half-life
6.0
(5.2 to 9.3)
7.6
(4.4 to 19.1)
8.1
(5.1 to 9.9)
2.5
(1.5 to 4.9)
11.Secondary Outcome
Title Maximum Plasma Drug Concentration/Minimum Inhibitory Concentration (Cmax/MIC)
Hide Description [Not Specified]
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. One subject in the moxifloxacin arm was discontinued from the study before day 5 and did not undergo PK sampling.
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description:
Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/day x 7 days
Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/day x 7 days
Overall Number of Participants Analyzed 10 10 9 10
Median (Inter-Quartile Range)
Unit of Measure: ug/ml
9.5
(8.4 to 11.3)
15.6
(12.2 to 16.6)
12.3
(9.6 to 13.4)
70.6
(64.0 to 76.2)
12.Secondary Outcome
Title Pharmacokinetic Parameters: Area Under the Curve (AUC) During First 12 and 24 Hours
Hide Description Area under the curve (AUC), from time 0-12 hours for INH or 0-24 hours for gatifloxacin, levofloxacin, and moxifloxacin.
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. Plasma samples were collected at 7 time points on the 5th day after beginning study drug monotherapy. One subject in the moxifloxacin arm was discontinued from the study before day 5 and did not undergo PK sampling.
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description:
Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/day x 7days
Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/day x 7 days
Overall Number of Participants Analyzed 10 10 9 10
Median (Full Range)
Unit of Measure: ug/h/ml
42.8
(31.7 to 51.0)
129.1
(103.4 to 358.3)
55.3
(36.0 to 79.1)
11.9
(7.1 to 37.4)
13.Secondary Outcome
Title Area Under the Curve During First 12 or 24 Hours / Minimum Inhibitory Concentration (AUC/MIC)
Hide Description Area Under the Curve (AUC) During First 12 or 24 Hours /Minimum Inhibitory Concentration. AUC reflects total drug (bound and unbound). MIC values were determined using protein-containing media.
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. One subject in the moxifloxacin arm was discontinued from the study before day 5 and did not undergo PK sampling
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description:
Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/day x 7 days
Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/day x 7 days
Overall Number of Participants Analyzed 10 10 9 10
Median (Inter-Quartile Range)
Unit of Measure: ug/ml
85.6
(70.7 to 89.7)
129.1
(121.0 to 145.0)
110.5
(98.9 to 121.6)
215.2
(177.4 to 329.6)
14.Secondary Outcome
Title Maximum Plasma Drug Concentration (Cmax)
Hide Description Maximum Plasma Drug Concentration (Cmax), given sampling scheme
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. One subject in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Median (Full Range)
Unit of Measure: ug/ml
3.3
(2.5 to 5.3)
15.0
(11.9 to 21.3)
19.4
(11.8 to 24.9)
15.Secondary Outcome
Title Time to Maximum Plasma Drug Concentration (Tmax) and Half-life
Hide Description [Not Specified]
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. One subject in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Median (Full Range)
Unit of Measure: hours
Tmax in h (apparent time of max plasma conc.)
1.0
(1.0 to 2.0)
1.5
(1.0 to 4.0)
1.0
(1.0 to 4.0)
Half-life
3.6
(1.1 to 4.5)
3.20
(1.5 to 5.0)
4.56
(2.1 to 7.0)
16.Secondary Outcome
Title Pharmacokinetic Parameters: Area Under the Curve During First 12 and 24 Hours
Hide Description Median pharmacokinetic parameters (range). AUC 0-12 and AUC 0-24 = area under the curve during the first 12 and 24 hours after dosing, respectively
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. One subject in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Median (Full Range)
Unit of Measure: ug/h/ml
AUC 0-12 (ug/h/ml)
17.0
(6.5 to 26.9)
87.0
(47.5 to 119.3)
116.4
(50.4 to 197.2)
AUC 0-24 (ug/h/ml)
19.2
(6.5 to 29.0)
96.9
(47.8 to 143.7)
232.9
(100.8 to 394.4)
17.Secondary Outcome
Title Maximum Plasma Drug Concentrations (Cmax), Adjusted for Free Drug Concentration
Hide Description Cmax adjusted for free drug concentrations after 5 days of monotherapy with study drugs
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine patients underwent pharmacokinetic (PK) sampling after receiving 5 daily doses of study drug. One subject in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Median (Full Range)
Unit of Measure: ug/ml
3.1
(2.5 to 4.8)
10.3
(8.2 to 14.7)
13.4
(8.1 to 17.2)
18.Secondary Outcome
Title Maximum Plasma Drug Concentration/Minimum Inhibitory Concentration (Cmax/MIC) Adjusted for Free Drug Concentrations
Hide Description [Not Specified]
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine patients underwent pharmacodynamic sampling after receiving 5 daily doses of study drug. One subject in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Median (Inter-Quartile Range)
Unit of Measure: ug/ml
62.7
(51.0 to 77.3)
20.0
(10.2 to 21.9)
16.2
(14.3 to 23.0)
19.Secondary Outcome
Title Area Under the Curve (AUC) During First 12 and 24 Hours Adjusted for Free Drug Concentrations
Hide Description Median pharmacodynamic parameters (range) adjusted for free drug concentrations. AUC 0-12 and AUC 0-24 = area under the curve during the first 12 and 24 hours after dosing, respectively
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine patients underwent pharmacodynamic (PD) sampling after receiving 5 daily doses of study drug. One subject in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Median (Inter-Quartile Range)
Unit of Measure: ug/h/ml
AUC 0-12
15.3
(5.8 to 24.2)
60.1
(32.8 to 82.3)
80.3
(34.8 to 136.1)
AUC 0-24
17.2
(5.8 to 26.1)
66.8
(33.0 to 99.2)
160.7
(134.4 to 225.8)
20.Secondary Outcome
Title Area Under the Curve (AUC) Adjusted for Free Drug Concentrations/Minimum Inhibitory Concentration (MIC)
Hide Description Area Under the Curve 0-12 (AUC 0-12) Adjusted for Free Drug Concentrations/Minimum Inhibitory Concentration (MIC) and AUC 0-24/MIC
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine patients underwent pharmacodynamic (PD) sampling after receiving 5 daily doses of study drug. One subject in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid, 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 9
Median (Inter-Quartile Range)
Unit of Measure: ug/h/ml
AUC 0-12/MIC
306.7
(229.3 to 405.2)
107.8
(63.4 to 126.3)
121.6
(79.8 to 141.6)
AUC 0-24/MIC
344.6
(249.4 to 449.2)
116.2
(71.0 to 138.4)
243.2
(159.7 to 283.2)
21.Secondary Outcome
Title Percent Dosing Interval Above Minimum Inhibitory Concentration (MIC)
Hide Description Determined by linear extrapolation of concentration-versus-time curve to intersection with MIC.
Time Frame Day 5 (7 time points)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine patients underwent pharmacodynamic (PD) sampling after receiving 5 daily doses of study drug. One subject in the linezolid twice daily arm withdrew from the study after randomization before receiving any doses of study drug.
Arm/Group Title Isoniazid (INH) 300 mg/Day Linezolid 600 mg/Once Daily Linezolid 600 mg/Twice Daily
Hide Arm/Group Description:
Isoniazid (INH) 300 mg/day x 7 days
Linezolid 600 mg/day x 7 days
Linezolid 600 mg q12h x 7 days
Overall Number of Participants Analyzed 10 10 10
Mean (Inter-Quartile Range)
Unit of Measure: Percentage
95.5
(76.4 to 100)
62.8
(54.6 to 77.0)
100.0
(100 to 100)
Time Frame Adverse event data were collected from February 2004 through October 2007.
Adverse Event Reporting Description Patients reported adverse events at scheduled or unscheduled visits. Adverse event forms were completed by medical officers on site.
 
Arm/Group Title Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Linezolid 600 mg / Once Daily Linezolid 600 mg / Twice Daily Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Hide Arm/Group Description Gatifloxacin 400 mg/day x 7 days Levofloxacin 1000 mg/day x 7days Linezolid 600 mg/once daily x 7days Linezolid 600 mg twice daily x 7 days Moxifloxacin 400 mg/day x 7 days Isoniazid (INH) 300 mg/day x 7 days
All-Cause Mortality
Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Linezolid 600 mg / Once Daily Linezolid 600 mg / Twice Daily Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Linezolid 600 mg / Once Daily Linezolid 600 mg / Twice Daily Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/20 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Gatifloxacin 400 mg/Day Levofloxacin 1000 mg/Day Linezolid 600 mg / Once Daily Linezolid 600 mg / Twice Daily Moxifloxacin 400 mg/Day Isoniazid (INH) 300 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/10 (80.00%)      7/10 (70.00%)      8/10 (80.00%)      5/10 (50.00%)      7/10 (70.00%)      7/20 (35.00%)    
Blood and lymphatic system disorders             
Elevated Monocytes  1  0/10 (0.00%)  0 0/10 (0.00%)  0 2/10 (20.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/20 (0.00%)  0
Hematocrit Decreased  1  2/10 (20.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/20 (0.00%)  0
Hemoglobin Decreased  1  2/10 (20.00%)  2 0/10 (0.00%)  0 3/10 (30.00%)  3 0/10 (0.00%)  0 0/10 (0.00%)  0 0/20 (0.00%)  0
Gastrointestinal disorders             
Diarrhea * 1  1/10 (10.00%)  2 0/10 (0.00%)  0 2/10 (20.00%)  2 2/10 (20.00%)  2 3/10 (30.00%)  3 0/20 (0.00%)  0
Intestinal Ancyclostomiasis  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 2/20 (10.00%)  2
Intestinal Constipation  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  2 0/10 (0.00%)  0 0/20 (0.00%)  0
Intestinal Strongyloidiasis  1  0/10 (0.00%)  0 0/10 (0.00%)  0 2/10 (20.00%)  2 2/10 (20.00%)  2 0/10 (0.00%)  0 2/20 (10.00%)  2
General disorders             
Fever  1  0/10 (0.00%)  0 2/10 (20.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/20 (0.00%)  0
Sweating  1  2/10 (20.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/20 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Joint Pain  1  0/10 (0.00%)  0 2/10 (20.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 2/20 (10.00%)  2
Lumbar Pain  1  0/10 (0.00%)  0 1/10 (10.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/20 (0.00%)  0
Pain in Both Shoulders  1  0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/20 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Chest Pain  1  2/10 (20.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 2/20 (10.00%)  2
Rales (or Crackles)  1  4/10 (40.00%)  5 4/10 (40.00%)  6 0/10 (0.00%)  0 0/10 (0.00%)  0 6/10 (60.00%)  13 7/20 (35.00%)  17
Ronchi  1  2/10 (20.00%)  3 2/10 (20.00%)  2 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/20 (5.00%)  2
Wheezing  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 2/20 (10.00%)  2
Skin and subcutaneous tissue disorders             
Acne  1  3/10 (30.00%)  3 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/20 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.1)
The small sample size had limited power to detect small differences in EBA between study arms even though we enrolled patients with smear-positive TB and high sputum bacillary burden to improve chances of detecting differences between treatment arms.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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
Name/Title: John L. Johnson, M.D.
Organization: Case Western Reserve University, Tuberculosis Research Unit
Phone: (216) 368-1949
EMail: jlj@case.edu
Publications of Results:
ClinicalTrials.gov Identifier: NCT00396084     History of Changes
Other Study ID Numbers: 01-553
First Submitted: November 3, 2006
First Posted: November 6, 2006
Results First Submitted: November 19, 2008
Results First Posted: June 25, 2009
Last Update Posted: November 8, 2018