PA-824-CL-007: Phase IIa Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis

Study Overview
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Brief Summary
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The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of PA-824 at 200, 600, 1000 and 1200 mg per day in adult patients with newly diagnosed, uncomplicated, smear positive tuberculosis. A control group will receive standard TB treatment.

Official Title
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A Phase IIa Trial to Evaluate the Safety, Tolerability, Extended Early Bactericidal Activity and Pharmacokinetics of 14 Days' Treatment With Four Oral Doses of PA-824 in Adult Participants With Newly Diagnosed, Uncomplicated, Smear-Positive, Pulmonary Tuberculosis

Conditions
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Pulmonary Tuberculosis

Intervention / Treatment
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* Drug: PA-824


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent M/F 18-64 yo newly diagnosed pulmonary TB sputum positive adequate contraception Exclusion Criteria: poor health rifampicin resistance treatment with other anti TB agents in last 3 mos. extrapulmonary TB COPD neuropathy ECG wih QRS prolongation ove 120 msec CV disorder diabetes requiring insulin Metabolic disease drug/alcohol abuse pregnancy use of substances that are strong inhibitors/inducers of CYP450 use of ARV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>PA-824 200 mg/qd | Drug: PA-824<br>* 200 mg, 600 mg, 100 mg, 1200 mg qd<br>* Other names: Rifafour e-275;|
| Experimental: 2<br>PA-824 600 mg/qd | Drug: PA-824<br>* 200 mg, 600 mg, 100 mg, 1200 mg qd<br>* Other names: Rifafour e-275;|
| Experimental: 3<br>PA-824 1000 mg/qd | Drug: PA-824<br>* 200 mg, 600 mg, 100 mg, 1200 mg qd<br>* Other names: Rifafour e-275;|
| Experimental: 4<br>PA-824 1200 mg/qd | Drug: PA-824<br>* 200 mg, 600 mg, 100 mg, 1200 mg qd<br>* Other names: Rifafour e-275;|
| Active Comparator: 5<br>Rifafour e-275 mg | Drug: PA-824<br>* 200 mg, 600 mg, 100 mg, 1200 mg qd<br>* Other names: Rifafour e-275;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Bactericidal Activity (EBA) Measured as the Daily Rate of Change in log10 CFUs (Colony Forming Units) of M. Tuberculosis in Sputum on Solid Media (Days 0-14). |  | Day 0 and Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Bactericidal Activity (EBA) Measured as the Daily Rate of Change in log10 CFUs (Colony Forming Units) of M. Tuberculosis in Sputum on Solid Media (Days 0-2). |  | Day 0 and Day 2 | 
| Early Bactericidal Activity (EBA) Measured as the Daily Rate of Change in log10 CFUs (Colony Forming Units) of M. Tuberculosis in Sputum on Solid Media (Days 2-14). |  | Day 2 and Day 14 | 
| EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14) |  | Day 0 and Day 14 | 
| EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-2) |  | Day 0 and Day 2 | 
| EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 2-14) Show Description: [Not Specified] |  | Day 2 and Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early Bactericidal Activity, EBA, pulmonary tuberculosis, PA-824, Pretomanid, CL-007