Trial reportAntimicrobial agents and chemotherapy2010
Early bactericidal activity and pharmacokinetics of PA-824 in smear-positive tuberculosis patients.
Trial report in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Time Trends in Sputum Mycobacterial Load and Two-Day Bactericidal Activity of Isoniazid-Containing Antituberculosis Therapies.Antimicrobial agents and chemotherapy · 2017Pooled it
- Pooled it
- Population pharmacokinetics and target attainment of pretomanid in rifampicin-resistant tuberculosis patients.Scientific reports · 2026Trial
- Relative bioavailability of delamanid 50 mg tablets dispersed in water in healthy adult volunteers.British journal of clinical pharmacology · 2025Trial
- Assessing Pretomanid for Tuberculosis (APT), a Randomized Phase 2 Trial of Pretomanid-Containing Regimens for Drug-Sensitive Tuberculosis: 12-Week Results.American journal of respiratory and critical care medicine · 2023Trial
- Pretomanid dose selection for pulmonary tuberculosis: An application of multi-objective optimization to dosage regimen design.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Pretomanid Pharmacokinetics in the Presence of Rifamycins: Interim Results from a Randomized Trial among Patients with Tuberculosis.Antimicrobial agents and chemotherapy · 2021Trial
- Fourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2020Trial
- Long-Term Effects on QT Prolongation of Pretomanid Alone and in Combinations in Patients with Tuberculosis.Antimicrobial agents and chemotherapy · 2019Trial
- First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment.Antimicrobial agents and chemotherapy · 2019Trial
- Early Bactericidal Activity of AZD5847 in Patients with Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2016Trial
- A new trial design to accelerate tuberculosis drug development: the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP).BMC medicine · 2016Trial
- Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin.Antimicrobial agents and chemotherapy · 2014Trial
- Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis.PloS one · 2014Trial
- Effect of a high-calorie, high-fat meal on the bioavailability and pharmacokinetics of PA-824 in healthy adult subjects.Antimicrobial agents and chemotherapy · 2013Trial
- Phase II dose-ranging trial of the early bactericidal activity of PA-824.Antimicrobial agents and chemotherapy · 2012Trial
- The Structure, Properties, and Clinical Utility of Contezolid for Antituberculosis: A Narrative Review.Infectious diseases and therapy · 2026Review
- Hepatic safety of pretomanid- and pyrazinamide-containing regimens in TB Alliance clinical trials.IJTLD open · 2025Article
- Clinical Pharmacokinetics of Antitubercular Drugs in the Overweight and Obese Population: Implications for Dosage Adjustments.Clinical pharmacokinetics · 2025Review
- Pharmacology of emerging drugs for the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PA-824 is a novel nitroimidazo-oxazine being evaluated for its potential to improve tuberculosis (TB) therapy. This randomized study evaluated safety, tolerability, pharmacokinetics, and extended early bactericidal activity of PA-824 in drug-sensitive, sputum smear-positive, adult pulmonary tuberculosis patients. Fifteen patients per cohort received 1 of 4 doses of oral PA-824: 200, 600, 1,000, or 1,200 mg per day for 14 days. Eight subjects received once daily standard antituberculosis treatment as positive control. The primary efficacy endpoint was the mean rate of change in log CFU of Mycobacterium tuberculosis in sputum incubated on agar plates from serial overnight sputum collections, expressed as log10 CFU/day/ml (+/-standard deviation [SD]). The drug demonstrated increases that were dose linear but less than dose proportional in serum concentrations in doses from 200 to 1,000 mg daily. Dosing of 1,200 mg gave no additional exposure compared to 1,000 mg daily. The mean daily CFU fall under standard treatment was 0.148 (+/-0.055), consistent with that found in previous studies. The mean daily fall under PA-824 was 0.098 (+/-0.072) and was equivalent for all four dosages. PA-824 appeared safe and well tolerated; the incidence of adverse events potentially related to PA-824 appeared dose related. We conclude that PA-824 demonstrated bactericidal activity over the dose range of 200 to 1,200 mg daily over 14 days. Because maximum efficacy was unexpectedly achieved at the lowest dosage tested, the activity of lower dosages should now be explored.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.