Phase 2
N=69
Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (CL-010)
Pulmonary Tuberculosis
Bottom Line
View on ClinicalTrials.gov: NCT00944021 ↗Enrolled (actual)
69
Serious AEs
2.9%
Results posted
Mar 2016
Primary outcome: Primary: 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). — 0.063; 0.091; 0.078; 0.112 log10CFU/ml/day
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- PA-824 (Drug); Rifafour e-275 mg (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Global Alliance for TB Drug Development
- Primary completion
- Jan 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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). |
0.063; 0.091; 0.078; 0.112; 0.177 | — |
| SECONDARY 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). |
0.093; 0.111; -0.009; 0.160; 0.470 | — |
| SECONDARY 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). |
0.059; 0.088; 0.096; 0.104; 0.128 | — |
| SECONDARY Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14). |
2.621; 4.969; 4.633; 4.640; 13.364 | — |
| SECONDARY Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2). |
1.483; -1.345; 4.867; 3.096; 37.016 | — |
| SECONDARY Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14). |
2.958; 5.744; 4.594; 5.391; 9.422 | — |
| SECONDARY Pharmacokinetics- Maximum Observed Plasma Concentration (Cmax) (Day 1). |
465.3; 662.3; 994.7; 1183.0 | — |
| SECONDARY Pharmacokinetics- Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC 0 to Infinity) (Day 1). |
11923.94; 18408.59; 28654.83; 38485.04 | — |
| SECONDARY Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 1). |
16.142; 18.597; 19.005; 21.092 | — |
| SECONDARY Pharmacokinetics-Maximum Observed Plasma Concentration (Cmax) (Day 14). |
777.3; 1116.5; 1543.9; 2223.8 | — |
| SECONDARY Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 14). |
18.645; 19.274; 20.207; 23.811 | — |
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.
Eligibility Criteria
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).
Data sourced from ClinicalTrials.gov (NCT00944021). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.