Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (CL-010)

• Sponsor: Global Alliance for TB Drug Development (Other)
• Overall Status: Completed
• CT.gov ID: NCT00944021
• Collaborator: (none)
• Enrollment: 69
• Arms: 5
• Duration (Months): 9

Study Details

Study Description

Brief Summary

The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of PA-824 at 50, 100, 150 and 200 mg per day in adult patients with newly diagnosed, uncomplicated, smear positive tuberculosis (TB). A control group will receive standard TB treatment.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Tuberculosis	Drug: PA-824; Drug: PA-824; Drug: PA-824; Drug: Rifafour e-275 mg; Drug: PA-824	Phase 2

Detailed Description

The planned sample size of 15 participants per treatment group is in keeping with other Phase II trials of this type and accounts for the possibility of up to 3 drop-outs per arm, which based on previous studies of this type conducted at these sites, represents a conservative estimate of the expected drop-out rate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II Dose Ranging Trial to Evaluate the Extended Early Bactericidal Activity, Safety, Tolerability, and Pharmacokinetics of PA-824 in Adult Participants With Newly Diagnosed, Uncomplicated, Smear-Positive, Pulmonary Tuberculosis
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PA-824 50 mg/qd	Drug: PA-824; 50mg
Experimental: PA-824 100mg/qd	Drug: PA-824; 100mg
Experimental: PA-824 150mg/qd	Drug: PA-824; 150 mg
Experimental: PA-824 200mg/qd	Drug: PA-824; 200 mg
Active Comparator: Rifafour e-275mg	Drug: Rifafour e-275 mg; 275 mg

Outcome Measures

Primary Outcome Measures

1. Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14). [14 consecutive days of treatment]

Secondary Outcome Measures

1. Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2). [Two consecutive days of treatment]

2. Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14). [Days 2-14 of 14 consecutive days of treatment]

3. Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14). [Fourteen consecutive days of treatment]

4. Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2). [Two consecutive days of treatment]

5. Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14). [Days 2-14 of 14 consecutive days of treatment]

6. Pharmacokinetics- Maximum Observed Plasma Concentration (Cmax) (Day 1). [0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment]

7. Pharmacokinetics- Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC 0 to Infinity) (Day 1). [0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment]

8. Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 1). [0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment]

9. Pharmacokinetics-Maximum Observed Plasma Concentration (Cmax) (Day 14). [0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12,16, 24, and 30 hours post-dose on Day 14 of 14 consecutive days of treatment]

10. Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 14). [0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24 and 30 hours post-dose on Day 14 of 14 consecutive days of treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed Consent

• Body weight between 40 and 90 kg, inclusive.

• Newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary TB.

• A chest X-ray compatible with TB.

• Sputum positive

• Adequate volume of sputum

• Female participants of childbearing potential negative serum pregnancy and agree to use birth control

• Male participants must agree to use contraception throughout participation in the trial and for 12 weeks after last dose.

Exclusion Criteria:

• Poor general condition

• Rifampicin-resistant and/or Isoniazid-resistant

• MTB Treatment received within the 3 months prior

• Allergy to the IMP or related substances

• Evidence of extrathoracic TB

• A history of previous TB

• Evidence of serious lung conditions other than TB or uncontrolled obstructive bronchial disease

• History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic examination

• Any evidence of renal impairment

• For males, any evidence or history of abnormality in the reproductive system

• History and/or presence (or evidence) of neuropathy or epilepsy.

• Clinically relevant changes in the ECG

• A history of or current clinically relevant cardiovascular disorder

• Concomitant use of any drug known to prolong QTc interval

• Diabetics using insulin

• Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).

• Any diseases or conditions in which the use of the standard TB drugs or any of their components is contra-indicated, including but not limited to allergy to any TB drug, their component or to the IMP.

• Any disease or conditions in which any of the medicinal products listed in the section pertaining to prohibited medication is used.

• alcohol or drug abuse

• Administration of an IMP prior to Visit 1, within 5 half-lives for that IMP if known. If the half-life of the IMP is unknown within 1 month.

• Pregnant, breast-feeding, or planning to conceive or father a child within twelve weeks of cessation of treatment for males and within one week of cessation of treatment for females.

• Use of any drugs or substances within 30 days prior to dosing known to be strong inhibitors or inducers of cytochrome P450 enzymes

• Any therapeutic agents known to alter any major organ function (e.g., barbiturates, opiates, phenothiazines, cimetidine) within 30 days prior to dosing.

• glucocorticoids within one year prior to dosing.

• HIV infection with helper/inducer T lymphocyte (CD4 cell) count of less than or equal to 300x10-6/L.

• Receiving antiretroviral therapy (ART).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Global Alliance for TB Drug Development

Investigators

• Principal Investigator: Andreas Diacon, MD, Karl Bremer Hospital
• Principal Investigator: Rodney Dawson, MD, University of Cape Town Lung Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Global Alliance for TB Drug Development
• ClinicalTrials.gov Identifier: NCT00944021
• Other Study ID Numbers: PA-824-CL-010
• First Posted: Jul 22, 2009
• Last Update Posted: Sep 20, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by Global Alliance for TB Drug Development: Early Bactericidal Activity; EBA; Pulmonary Tuberculosis; PA-824; pretomanid
• Additional relevant MeSH terms: Tuberculosis; Tuberculosis, Pulmonary

Study Results

Participant Flow

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd	Rifafour e-275mg
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet	Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).
Period Title: Overall Study
STARTED	15	15	15	16	8
COMPLETED	14	15	15	16	8
NOT COMPLETED	1	0	0	0	0

Baseline Characteristics

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd	Rifafour e-275mg	Total
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet	Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).	Total of all reporting groups
Overall Participants	15	15	15	16	8	69
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	15 100%	15 100%	16 100%	8 100%	69 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.5 (9.76)	29.6 (9.28)	26.9 (8.91)	25.3 (6.18)	33.3 (14.09)	28.6 (9.45)
Sex: Female, Male (Count of Participants)
Female	8 53.3%	7 46.7%	8 53.3%	9 56.3%	2 25%	34 49.3%
Male	7 46.7%	8 53.3%	7 46.7%	7 43.8%	6 75%	35 50.7%
Region of Enrollment (participants) [Number]
South Africa	15 100%	15 100%	15 100%	16 100%	8 100%	69 100%

Outcome Measures

1. Primary Outcome

Title	Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).
Time Frame	14 consecutive days of treatment

Outcome Measure Data

Analysis Population Description

All randomized subjects. Some of the EBA values could not be calculated due to missing results. The analysis population is the number of patients for whom the results were available for this time period and therefore for whom the relevant EBA could be calculated.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd	Rifafour e-275mg
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet	Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).
Measure Participants	12	15	14	14	8
Mean (Standard Deviation) [log10CFU/ml/day]	0.063 (0.058)	0.091 (0.073)	0.078 (0.074)	0.112 (0.070)	0.177 (0.042)

2. Secondary Outcome

Title	Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).
Time Frame	Two consecutive days of treatment

Outcome Measure Data

Analysis Population Description

All randomized subjects. Some of the EBA values could not be calculated due to missing results. The analysis population is the number of patients for whom the results were available for this time period and therefore for whom the relevant EBA could be calculated.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd	Rifafour e-275mg
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet	Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).
Measure Participants	14	15	15	14	8
Mean (Standard Deviation) [log10CFU/ml/day]	0.093 (0.211)	0.111 (0.332)	-0.009 (0.290)	0.160 (0.255)	0.470 (0.316)

3. Secondary Outcome

Title	Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).
Time Frame	Days 2-14 of 14 consecutive days of treatment

Outcome Measure Data

Analysis Population Description

All randomized subjects. Some of the EBA values could not be calculated due to missing results. The analysis population is the number of patients for whom the results were available for this time period and therefore for whom the relevant EBA could be calculated.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd	Rifafour e-275mg
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet	Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).
Measure Participants	12	15	14	14	8
Mean (Standard Deviation) [log10CFU/ml/day]	0.059 (0.060)	0.088 (0.085)	0.096 (0.98)	0.104 (0.083)	0.128 (0.070)

4. Secondary Outcome

Title	Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14).
Time Frame	Fourteen consecutive days of treatment

Outcome Measure Data

Analysis Population Description

All randomized subjects. Some of the TTP values could not be calculated due to missing results. The population is the number of patients for whom the results were available for this time period and therefore for whom the relevant TTP could be calculated.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd	Rifafour e-275mg
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet	Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).
Measure Participants	13	14	15	16	8
Mean (Standard Deviation) [hours/day]	2.621 (2.534)	4.969 (3.644)	4.633 (3.687)	4.640 (3.447)	13.364 (3.979)

5. Secondary Outcome

Title	Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2).
Time Frame	Two consecutive days of treatment

Outcome Measure Data

Analysis Population Description

All randomized subjects. Some of the TTP values could not be calculated due to missing results. The population is the number of patients for whom the results were available for this time period and therefore for whom the relevant TTP could be calculated.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd	Rifafour e-275mg
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet	Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).
Measure Participants	15	14	15	13	8
Mean (Standard Deviation) [hours/day]	1.483 (8.153)	-1.345 (8.586)	4.867 (12.755)	3.096 (8.202)	37.016 (5.639)

6. Secondary Outcome

Title	Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14).
Time Frame	Days 2-14 of 14 consecutive days of treatment

Outcome Measure Data

Analysis Population Description

All randomized subjects. Some of the TTP values could not be calculated due to missing results. The population is the number of patients for whom the results were available for this time period and therefore for whom the relevant TTP could be calculated.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd	Rifafour e-275mg
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet	Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).
Measure Participants	13	15	15	13	8
Mean (Standard Deviation) [hours/day]	2.958 (2.652)	5.744 (3.973)	4.594 (5.035)	5.391 (3.608)	9.422 (4.367)

7. Secondary Outcome

Title	Pharmacokinetics- Maximum Observed Plasma Concentration (Cmax) (Day 1).
Time Frame	0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment

Outcome Measure Data

Analysis Population Description

All PA-824 patients who received at least one administration of the investigational drug, had at least one measured concentration after the start of treatment for at least one PK analysis and had no major events affecting the integrity of the PK data.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet
Measure Participants	15	15	15	16
Mean (Standard Deviation) [ng/mL]	465.3 (150.6)	662.3 (167.8)	994.7 (305.7)	1183.0 (382.5)

8. Secondary Outcome

Title	Pharmacokinetics- Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC 0 to Infinity) (Day 1).
Time Frame	0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment

Outcome Measure Data

Analysis Population Description

All PA-824 patients who received at least one administration of the investigational drug, had at least one measured concentration after the start of treatment for at least one PK analysis and had no major events affecting the integrity of the PK data.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet
Measure Participants	15	15	15	16
Mean (Standard Deviation) [ng * hour/mL]	11923.94 (4512.94)	18408.59 (7665.35)	28654.83 (10924.23)	38485.04 (16606.96)

9. Secondary Outcome

Title	Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 1).
Time Frame	0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment

Outcome Measure Data

Analysis Population Description

All PA-824 patients who received at least one administration of the investigational drug, had at least one measured concentration after the start of treatment for at least one PK analysis and had no major events affecting the integrity of the PK data.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet
Measure Participants	15	15	15	16
Mean (Standard Deviation) [hours]	16.142 (5.501)	18.597 (9.459)	19.005 (7.349)	21.092 (6.490)

10. Secondary Outcome

Title	Pharmacokinetics-Maximum Observed Plasma Concentration (Cmax) (Day 14).
Time Frame	0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12,16, 24, and 30 hours post-dose on Day 14 of 14 consecutive days of treatment

Outcome Measure Data

Analysis Population Description

All PA-824 patients who received at least one administration of the investigational drug, had at least one measured concentration after the start of treatment for at least one PK analysis and had no major events affecting the integrity of the PK data.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet
Measure Participants	15	15	15	16
Mean (Standard Deviation) [ng/mL]	777.3 (250.7)	1116.5 (357.4)	1543.9 (511.4)	2223.8 (734.5)

11. Secondary Outcome

Title	Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 14).
Time Frame	0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24 and 30 hours post-dose on Day 14 of 14 consecutive days of treatment

Outcome Measure Data

Analysis Population Description

All PA-824 patients who received at least one administration of the investigational drug, had at least one measured concentration after the start of treatment for at least one PK analysis and had no major events affecting the integrity of the PK data.

Arm/Group Title	PA-824 50 mg/qd	PA-824 100mg/qd	PA-824 150mg/qd	PA-824 200mg/qd
Arm/Group Description	PA-824 : 50mg oral tablet	PA-824 : 100mg oral tablet	PA-824 : 150 mg oral tablet	PA-824 : 200 mg oral tablet
Measure Participants	15	15	15	16
Mean (Standard Deviation) [hour]	18.645 (5.394)	19.274 (10.249)	20.207 (5.288)	23.811 (8.067)

Adverse Events

Time Frame	180 days
Adverse Event Reporting Description	Adverse events were collected from the time a patient signed the informed consent until day 29. From day 29 through day 180, only opthalmologic related adverse events and serious adverse events were collected. Data reported are treatment-emergent adverse events.
Arm/Group Title	PA-824 50 mg/qd		PA-824 100mg/qd		PA-824 150mg/qd		PA-824 200mg/qd		Rifafour e-275mg
Arm/Group Description	PA-824 : 50mg oral tablet		PA-824 : 100mg oral tablet		PA-824 : 150 mg oral tablet		PA-824 : 200 mg oral tablet		Rifafour e-275 mg : A once daily dose dependent on the patients weight 30 to 37 kg - 2 tablets, 38 to 54 kg - 3 tablets, 55 to 70 kg - 4 tablets or 71 kg and over - 5 tablets).
All Cause Mortality
	PA-824 50 mg/qd		PA-824 100mg/qd		PA-824 150mg/qd		PA-824 200mg/qd		Rifafour e-275mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PA-824 50 mg/qd		PA-824 100mg/qd		PA-824 150mg/qd		PA-824 200mg/qd		Rifafour e-275mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		1/16 (6.3%)		0/8 (0%)
Infections and infestations
Pneumonia	0/15 (0%)		0/15 (0%)	0	0/15 (0%)	0	1/16 (6.3%)	0	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/15 (6.7%)		0/15 (0%)	0	0/15 (0%)	0	0/16 (0%)	0	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	PA-824 50 mg/qd		PA-824 100mg/qd		PA-824 150mg/qd		PA-824 200mg/qd		Rifafour e-275mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/15 (66.7%)		5/15 (33.3%)		5/15 (33.3%)		7/16 (43.8%)		4/8 (50%)
Cardiac disorders
Bundle branch block left	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Tachycardia	1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Eye disorders
Lenticular opacities	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/16 (0%)		1/8 (12.5%)
Ocular hyperaemia	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/16 (0%)		0/8 (0%)
Gastrointestinal disorders
Abdominal pain	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Abdominal pain upper	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Diarrhoea	0/15 (0%)		0/15 (0%)		0/15 (0%)		1/16 (6.3%)		0/8 (0%)
Gingivitis	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/16 (0%)		0/8 (0%)
Nausea	1/15 (6.7%)		0/15 (0%)		1/15 (6.7%)		0/16 (0%)		1/8 (12.5%)
Vomiting	1/15 (6.7%)		0/15 (0%)		1/15 (6.7%)		0/16 (0%)		1/8 (12.5%)
General disorders
Chills	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Fatigue	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Pyrexia	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Infections and infestations
Vaginal infection	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Investigations
Haemoglobin decreased	0/15 (0%)		0/15 (0%)		0/15 (0%)		1/16 (6.3%)		0/8 (0%)
Heart rate increased	0/15 (0%)		1/15 (6.7%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Hepatic enzyme increased	0/15 (0%)		0/15 (0%)		0/15 (0%)		1/16 (6.3%)		0/8 (0%)
Metabolism and nutrition disorders
Hyponatraemia	0/15 (0%)		0/15 (0%)		0/15 (0%)		1/16 (6.3%)		0/8 (0%)
Nervous system disorders
Dizziness	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Headache	2/15 (13.3%)		0/15 (0%)		0/15 (0%)		1/16 (6.3%)		0/8 (0%)
Neuropathy peripheral	0/15 (0%)		0/15 (0%)		0/15 (0%)		1/16 (6.3%)		0/8 (0%)
Psychiatric disorders
Euphoric mood	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/16 (0%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	0/15 (0%)		0/15 (0%)		1/15 (6.7%)		0/16 (0%)		0/8 (0%)
Pleuritic pain	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/16 (0%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders
Pruritis	1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)		0/16 (0%)		1/8 (12.5%)
Pruritus generalised	1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)		1/16 (6.3%)		0/8 (0%)
Rash	1/15 (6.7%)		0/15 (0%)		1/15 (6.7%)		0/16 (0%)		0/8 (0%)
Rash macular	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/16 (0%)		0/8 (0%)
Rash papular	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		3/16 (18.8%)		0/8 (0%)
Urticaria	1/15 (6.7%)		0/15 (0%)		0/15 (0%)		0/16 (0%)		1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.