Diurnal variation in DLCO and non-standardized study procedures may cause a false positive safety signal in clinical trials. (January 2022)

• Record Type: Journal Article
• Authors: Kirla, Krishna Tulasi; Nemes, Szilárd; Betts, Joanne; Kristensson, Cecilia; Mo, John; Asimus, Sara; Sadiq, Muhammad Waqas; Redlich, Elke; Koernicke, Thomas; Fuhr, Rainard; Brailsford, Wayne; Keen, Christina; Hagberg, Anette; Mäenpää, Jukka
• Is Part Of: Respiratory medicine. Volume 191(2022)
• Publication Date: 2022-01
• Subjects: DLCO -- Diurnal variation -- False positive safety signal -- Pneumonitis -- Timing standardization -- Inhaled PI3K inhibitor; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2021.106705
• Languages: English
• ISSNs: 0954-6111

Abstract

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. 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.