Diurnal variation in DLCO and non-standardized study procedures may cause a false positive safety signal in clinical trials - 25/01/22
Abstract |
Diffusing capacity for carbon monoxide (DLCO) was measured in a phase I single ascending dose study after inhalation of AZD8154 or placebo in healthy participants at baseline (DLCOBaseline) and follow-up (DLCOFollow-up) 6 days after dosing. Initially, DLCOFollow-up timepoint was 2 h earlier than the DLCOBaseline timepoint and clinically significant decreases in DLCOFollow-up (absolute change up to 19% from baseline and DLCO%predicted values less than 70) were observed then. The observed reduction in DLCOFollow-up was confirmed as a false positive finding after alignment of DLCO timings. As a consequence, when DLCO is used in clinical studies, measurements should be strictly standardized in relation to time of the day.
Le texte complet de cet article est disponible en PDF.Highlights |
• | DLCO measurements might be affected by various factors in healthy volunteers. |
• | Measuring DLCO at different timings of a day led to significant decreased values. |
• | Factors affecting cardiac output should be standardized at each DLCO timepoint. |
Keywords : DLCO, Diurnal variation, False positive safety signal, Pneumonitis, Timing standardization, Inhaled PI3K inhibitor
Plan
Vol 191
Article 106705- janvier 2022 Retour au numéro
Article précédent
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