Trial reportCPT: pharmacometrics & systems pharmacology2021
Exposure-safety analysis of QTc interval and transaminase levels following bedaquiline administration in patients with drug-resistant tuberculosis.
Trial report in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Effect of HIV on bedaquiline and delamanid pharmacokinetics in patients with multidrug-resistant TB.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2025Trial
- Population pharmacokinetic and exposure-response study of a novel anti-tuberculosis drug to inform its dosage design in phase III clinical trial.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2025Trial
- Cardiac safety of bedaquiline, delamanid and moxifloxacin co-administered with or without varying doses of sutezolid or delpazolid for the treatment of drug-susceptible TB.The Journal of antimicrobial chemotherapy · 2025Trial
- Establishing the Exposure-QT Relationship During Bedaquiline Treatment Using a Time-Varying Tuberculosis-Specific Correction Factor (QTcTBT).CPT: pharmacometrics & systems pharmacology · 2025Trial
- Assessing Prolongation of the Corrected QT Interval with Bedaquiline and Delamanid Coadministration to Predict the Cardiac Safety of Simplified Dosing Regimens.Clinical pharmacology and therapeutics · 2022Trial
- Exposure-safety analysis of QTc interval and transaminase levels following bedaquiline administration in patients with drug-resistant tuberculosis.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Application of an Open-Source Modular Framework for Pharmacokinetic, Pharmacodynamic, and Safety Simulations to Anti-Tuberculosis Drugs.CPT: pharmacometrics & systems pharmacology · 2026Article
- Bedaquiline reloading strategies following interruptions during daily dosing.Antimicrobial agents and chemotherapy · 2026Article
- QT prolongation in participants receiving bedaquiline-containing regimens: analysis of data from Phase 3 STREAM Stage 2.IJTLD open · 2026Article
- An Interactive Pharmacokinetic-Pharmacodynamic Framework to Evaluate Bedaquiline Dose Modifications in Adults With Tuberculosis.CPT: pharmacometrics & systems pharmacology · 2026Article
- Exposure-QTc modeling of bedaquiline, pretomanid, and clofazimine in adults with tuberculosis.Antimicrobial agents and chemotherapy · 2026Article
- Analysis of Adverse Drug Reactions of Clofazimine Reported in the FDA Adverse Event Reporting System from 2004 to 2025 Q1.Infectious diseases and therapy · 2025Article
- Model-Informed Once-Daily Dosing Strategy for Bedaquiline and Delamanid in Children, Adolescents and Adults with Tuberculosis.Clinical pharmacology and therapeutics · 2025Article
- Development and validation of a time-varying correction factor for QT interval assessment in drug-resistant tuberculosis patients.International journal of antimicrobial agents · 2025Article
- HIV and body mass index are associated with prolonged corrected QT interval among people with drug-resistant tuberculosis on bedaquiline-containing regimen in Uganda.IJID regions · 2024Article
- The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation.International journal of antimicrobial agents · 2023Observational
- Predictions of Bedaquiline and Pretomanid Target Attainment in Lung Lesions of Tuberculosis Patients using Translational Minimal Physiologically Based Pharmacokinetic Modeling.Clinical pharmacokinetics · 2023Article
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
- Population pharmacokinetics and model-based dosing evaluation of bedaquiline in multidrug-resistant tuberculosis patients.Frontiers in pharmacology · 2023Article
- Pharmacogenetics of Between-Individual Variability in Plasma Clearance of Bedaquiline and Clofazimine in South Africa.The Journal of infectious diseases · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Bedaquiline (BDQ) has shown great value in the treatment of multidrug-resistant tuberculosis (MDR-TB) in recent years. However, exposure-safety relationships must be explored to extend the use of BDQ. Two reported safety findings for BDQ are prolongation of the QTc interval and elevation of transaminase levels. In this study, we investigated the potential relationships between BDQ and/or its main metabolite (M2) pharmacokinetic (PK) metrics and QTcF interval or transaminase levels in patients with MDR-TB using the approved dose regimen. Data from 429 patients with MDR-TB from two phase IIb studies were analyzed via nonlinear mixed-effects modeling. Individual model-predicted concentrations and summary PK metrics were evaluated, respectively, in the QTcF interval and transaminase level exposure-response models. Investigation of further covariate effects was performed in both models. M2 concentrations were found to be responsible for the drug-related QTcF increase in a model accounting for circadian rhythm patterns, time on study, effect of concomitant medication with QT liability, and patient demographics. Simulations with the final model suggested that doses higher than the approved dose (leading to increased M2 concentrations) are not expected to lead to a critical QTcF interval increase. No exposure-safety relationship could be described with transaminase levels despite previous reports of higher levels in patients treated with BDQ. The developed longitudinal models characterized the role of M2 concentrations in QTc interval prolongation and found no concentration dependency for transaminase level elevation, together suggesting that BDQ exposure at the high end of the observed range may not be associated with a higher risk of safety events.
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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.