ArticleThe European respiratory journal2023
Translational predictions of phase 2a first-in-patient efficacy studies for antituberculosis drugs.
Article in The European respiratory journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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Who cites it
11 citing papers in PubMed.
- Prospectively predicting BPaMZ phase IIb/III trial outcomes using a translational mouse-to-human platform.Antimicrobial agents and chemotherapy · 2024Trial
- Successful Translational Prediction of Bedaquiline's Phase 2a Clinical Trial Results against Tuberculosis: The Zebrafish as a New Approach Methodology.Clinical pharmacology and therapeutics · 2026Article
- Article
- Translational Modeling of BTZ-043 to Predict Phase 2A Efficacy and Evaluate Drug-Drug Interactions With Bedaquiline, Pretomanid, and Linezolid in Murine Models.The Journal of infectious diseases · 2025Article
- Article
- Tuberculosis: An Update for the Clinician.Respirology (Carlton, Vic.) · 2025Review
- GEODE: anFrontiers in pharmacology · 2025Article
- REVOLUTIONIZING TUBERCULOSIS REGIMEN DEVELOPMENT.Transactions of the American Clinical and Climatological Association · 2025Review
- Toward better cures forClinical microbiology reviews · 2024Review
- Dose optimization of TBI-223 for enhanced therapeutic benefit compared to linezolid in antituberculosis regimen.Nature communications · 2024Article
- stormTB: a web-based simulator of a murine minimal-PBPK model for anti-tuberculosis treatments.Frontiers in pharmacology · 2024Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundPhase 2a trials in tuberculosis typically use early bactericidal activity (EBA), the decline in sputum CFU over 14 days, as the primary end-point for testing the efficacy of drugs as monotherapy. However, the cost of phase 2a trials can range from USD 7 million to USD 19.6 million on average, while >30% of drugs fail to progress to phase 3. Better utilising pre-clinical data to predict and prioritise the most likely drugs to succeed will thus help to accelerate drug development and reduce costs. We aim to predict clinical EBA using pre-clinical METHODS AND
findingsFirst, mouse PK, PD and clinical PK models were compiled. Second, mouse PK-PD models were built to derive an exposure-response relationship. Third, translational prediction of clinical EBA studies was performed using mouse PK-PD relationships and informed by clinical PK models and species-specific protein binding. Presence or absence of clinical efficacy was accurately predicted from the mouse model. Predicted daily decreases of CFU in the first 2 days of treatment and between day 2 and day 14 were consistent with clinical observations.
conclusionThis platform provides an innovative solution to inform or even replace phase 2a EBA trials, to bridge the gap between mouse efficacy studies and phase 2b and phase 3 trials, and to substantially accelerate drug development.
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