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

This study has been completed.

Study NCT00396084 Information provided by National Institute of Allergy and Infectious Diseases (NIAID)

First Received: November 3, 2006 Last Updated: November 19, 2009 History of Changes

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Parallel Assignment
Condition:	Tuberculosis
Interventions:	Drug: Gatifloxacin Drug: Isoniazid Drug: Levofloxacin Drug: Linezolid Drug: Moxifloxacin

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
Gatifloxacin 400 mg/Day	Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/Day	Levofloxacin 1000 mg/day x 7days
Linezolid 600 mg / Once Daily	Linezolid 600 mg/once daily x 7days
Linezolid 600 mg / Twice Daily	Linezolid 600 mg twice daily x 7 days
Moxifloxacin 400 mg/Day	Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/Day	Isoniazid (INH) 300 mg/day x 7 days

Participant Flow: Overall Study

	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
STARTED	10	10	10	10	10	20
COMPLETED	10	10	10	9	9	18
NOT COMPLETED	0	0	0	1	1	2
Adverse Event	0	0	0	0	1	2
Withdrawal by Subject	0	0	0	1	0	0

Baseline Characteristics

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Reporting Groups

	Description
Gatifloxacin 400 mg/Day	Gatifloxacin 400 mg/day x 7 days
Levofloxacin 1000 mg/Day	Levofloxacin 1000 mg/day x 7days
Linezolid 600 mg / Once Daily	Linezolid 600 mg/once daily x 7days
Linezolid 600 mg / Twice Daily	Linezolid 600 mg twice daily x 7 days
Moxifloxacin 400 mg/Day	Moxifloxacin 400 mg/day x 7 days
Isoniazid (INH) 300 mg/Day	Isoniazid (INH) 300 mg/day x 7 days

Baseline Measures

	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
Number of Participants [units: participants]	10	10	10	10	10	20	70
Age [units: participants]
<=18 years	0	0	0	0	0	0	0
Between 18 and 65 years	10	10	10	10	10	20	70
>=65 years	0	0	0	0	0	0	0
Age [units: years] Median ( Inter-Quartile Range )	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 )
Gender [units: participants]
Female	1	2	2	2	1	3	11
Male	9	8	8	8	9	17	59
Region of Enrollment [units: participants]
Brazil	10	10	10	10	10	20	70

Outcome Measures

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1. Primary:

Sputum Bacillary Loads: Adjusted Area Under the Curve (aAUC) [ Study drug administration duration - 7 days monotherapy ]

Show Outcome Measure 1

2. Primary:

Difference in Sputum Bacillary Loads: Early Bactericidal Activity (EBA) Days 0 to 2; Fluoroquinolones/Isoniazid (INH) Comparison [ Day 0 to Day 2 Monotherapy ]

Show Outcome Measure 2

3. Primary:

Extended Early Bactericidal Activity (EBA) From Days 2 to 7; Fluoroquinolones/Isoniazid (INH) Comparison [ Day 2 to Day 7 Monotherapy ]

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4. Primary:

Sputum Bacillary Loads: Adjusted Area Under the Curve (aAUC) [ Study drug administration duration - 7 days monotherapy ]

Show Outcome Measure 4

5. Primary:

Difference in Sputum Bacillary Loads: Early Bactericidal Activity (EBA) Days 0 to 2; Linezolid Once Daily/Linezolid Twice Daily/Isoniazid (INH) Comparison [ Day 0 to Day 2 Monotherapy ]

Show Outcome Measure 5

6. Primary:

Difference in Sputum Bacillary Loads: Extended Early Bactericidal Activity (EBA) From Days 2 to 7; Linezolid Once Daily/Linezolid Twice Daily/INH Comparison [ Day 2 to Day 7 Monotherapy ]

Show Outcome Measure 6

7. Secondary:

Maximum Plasma Drug Concentration (Cmax) [ Day 5 (7 time points) ]

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8. Secondary:

Time to Maximum Plasma Drug Concentration (Tmax) and Half-life [ Day 5 (7 time points) ]

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9. Secondary:

Maximum Plasma Drug Concentration/Minimum Inhibitory Concentration (Cmax/MIC) [ Day 5 (7 time points) ]

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10. Secondary:

Pharmacokinetic Parameters: Area Under the Curve (AUC) During First 12 and 24 Hours [ Day 5 (7 time points) ]

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11. Secondary:

Area Under the Curve During First 12 or 24 Hours / Minimum Inhibitory Concentration (AUC/MIC) [ Day 5 (7 time points) ]

Show Outcome Measure 11

12. Secondary:

Maximum Plasma Drug Concentration (Cmax) [ Day 5 (7 time points) ]

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13. Secondary:

Time to Maximum Plasma Drug Concentration (Tmax) and Half-life [ Day 5 (7 time points) ]

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14. Secondary:

Pharmacokinetic Parameters: Area Under the Curve During First 12 and 24 Hours [ Day 5 (7 time points) ]

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15. Secondary:

Maximum Plasma Drug Concentrations (Cmax), Adjusted for Free Drug Concentration [ Day 5 (7 time points) ]

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16. Secondary:

Maximum Plasma Drug Concentration/Minimum Inhibitory Concentration (Cmax/MIC) Adjusted for Free Drug Concentrations [ Day 5 (7 time points) ]

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17. Secondary:

Area Under the Curve (AUC) During First 12 and 24 Hours Adjusted for Free Drug Concentrations [ Day 5 (7 time points) ]

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18. Secondary:

Area Under the Curve (AUC) Adjusted for Free Drug Concentrations/Minimum Inhibitory Concentration (MIC) [ Day 5 (7 time points) ]

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19. Secondary:

Percent Dosing Interval Above Minimum Inhibitory Concentration (MIC) [ Day 5 (7 time points) ]

Show Outcome Measure 19