Diurnal variation in DLCO and non-standardized study procedures may cause a false positive safety signal in clinical trials

Respir Med. 2022 Jan:191:106705. doi: 10.1016/j.rmed.2021.106705. Epub 2021 Dec 2.

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.

Keywords: DLCO; Diurnal variation; False positive safety signal; Inhaled PI3K inhibitor; Pneumonitis; Timing standardization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Carbon Monoxide*
  • Circadian Rhythm
  • Clinical Trials as Topic
  • Humans
  • Pulmonary Diffusing Capacity*

Substances

  • Carbon Monoxide