Power to identify exposure‐response relationships in phase IIa pulmonary tuberculosis trials with multi‐dimensional bacterial load modeling

Autor: Simon E. Koele, Thomas P. C. Dorlo, Caryn M. Upton, Rob E. Aarnoutse, Elin M. Svensson
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: CPT: Pharmacometrics & Systems Pharmacology, Vol 13, Iss 3, Pp 374-385 (2024)
Druh dokumentu: article
ISSN: 2163-8306
DOI: 10.1002/psp4.13089
Popis: Abstract Adequate power to identify an exposure‐response relationship in a phase IIa clinical trial for pulmonary tuberculosis (TB) is important for dose selection and design of follow‐up studies. Currently, it is not known what response marker provides the pharmacokinetic‐pharmacodynamic (PK‐PD) model more power to identify an exposure‐response relationship. We simulated colony‐forming units (CFU) and time‐to‐positivity (TTP) measurements for four hypothetical drugs with different activity profiles for 14 days. The power to identify exposure‐response relationships when analyzing CFU, TTP, or combined CFU + TTP data was determined at 60 total participants, or with 25 out of 60 participants in the lowest and highest dosing groups (unbalanced design). For drugs with moderate bactericidal activity, power was low (
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