Reducing the variability of DLCO measurements in clinical trials

Introduction: Measuring diffusing capacity of the lung for carbon monoxide (DLCO) facilitates the diagnosis, classification and monitoring of various lung diseases, and may also be used for safety signal detection in clinical drug development. However, other factors such as exercise, supine position, and diurnal variations may affect the gas transfer and impact the DLCO measurements. Aim: To measure DLCO in healthy subjects receiving a novel inhaled drug or placebo. Methods: In a Phase I, single ascending dose study, DLCO was measured at baseline (Day -1) and at follow up (Day 6) after inhalation the novel drug or placebo, cohort 1-6. For practical reasons, the DLCO measurements were performed at 11 am on Day -1 and at 9 am on Day 6. After Cohort 2, standardization of the assessments was introduced and the assessments were done at the same time of the day. Further adjustments were made from Cohort 4 ensuring the same timeframe between DLCO assessments and preceding meal. Results: Changes in DLCO from baseline to follow per cohort are presented in Table 1. A decline in DLCO was noted for all subjects in Cohort 1 and 2 including placebo. After standardization of timing of the assessment less variability was seen, some subjects had an increase while other had a decrease. No changes were observed in subjects’ spirometry measurements. Conclusions: When measuring DLCO in clinical studies, the procedures should be standardized with regards to time of the day and in relation to timing of factors such as diet and physical activity.