Trial reportAntimicrobial agents and chemotherapy2012
Phase II dose-ranging trial of the early bactericidal activity of PA-824.
Trial report in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00944021 (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), which is not on this map. Cited by 66 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- Diabetes mellitus comorbidity in patients enrolled in tuberculosis drug efficacy trials around the world: A systematic review.British journal of clinical pharmacology · 2019Pooled it
- Time Trends in Sputum Mycobacterial Load and Two-Day Bactericidal Activity of Isoniazid-Containing Antituberculosis Therapies.Antimicrobial agents and chemotherapy · 2017Pooled it
- Population pharmacokinetics and target attainment of pretomanid in rifampicin-resistant tuberculosis patients.Scientific reports · 2026Trial
- 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
- Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2020Trial
- 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
- 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
- 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
- Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis.Antimicrobial agents and chemotherapy · 2013Trial
- Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin: Mechanisms of Action, Drug Interactions, Adverse Effects and Use in Special Situations.Microorganisms · 2026Review
- Mouse models of tuberculosis uniformly featuring hypoxic necrotic lesions and poor response to chemotherapy.Infection and immunity · 2026Article
- Mouse Models Uniformly Featuring Human-like Lesions Harboring Drug-tolerantbioRxiv : the preprint server for biology · 2025Article
- Hepatic safety of pretomanid- and pyrazinamide-containing regimens in TB Alliance clinical trials.IJTLD open · 2025Article
- Estimating the Early Transmission Inhibition of New Treatment Regimens for Drug-Resistant Tuberculosis.The Journal of infectious diseases · 2025Article
- Pharmacology of emerging drugs for the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Review
- Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024Review
- Translational predictions of phase 2a first-in-patient efficacy studies for antituberculosis drugs.The European respiratory journal · 2023Article
6 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
11 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PA-824 is a novel nitroimidazo-oxazine under evaluation as an antituberculosis agent. A dose-ranging randomized study was conducted to evaluate the safety, tolerability, pharmacokinetics, and early bactericidal activity of PA-824 in drug-sensitive, sputum smear-positive adult pulmonary-tuberculosis patients to find the lowest dose giving optimal bactericidal activity (EBA). Fifteen patients per cohort received oral PA-824 in doses of 50 mg, 100 mg, 150 mg, or 200 mg per kg body weight per day for 14 days. Eight subjects received once-daily standard antituberculosis treatment with isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) as a positive control. The primary efficacy endpoint was the mean rate of decline in log CFU of Mycobacterium tuberculosis in sputum incubated on agar plates from serial overnight sputum collections, expressed as log(10) CFU/day/ml sputum (± standard deviation). The mean 14-day EBA of HRZE was consistent with previous studies (0.177 ± 0.042), and that of PA-824 at 50 mg, 100 mg, 150 mg, and 200 mg was 0.063 ± 0.058, 0.091 ± 0.073, 0.078 ± 0.074, and 0.112 ± 0.070, respectively. Although the study was not powered for testing the difference between arms, there was a trend toward significance, indicating a lower EBA at the 50-mg dose. Serum PA-824 levels were approximately dose proportional with respect to the area under the time-concentration curve. All doses were safe and well tolerated with no dose-limiting adverse events or clinically significant QTc changes. A dose of 100 mg to 200 mg PA-824 daily appears to be safe and efficacious and will be further evaluated as a component of novel antituberculosis regimens for drug-sensitive and drug-resistant tuberculosis.
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Registered trials
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.