RT Journal Article SR Electronic T1 Validation of FEV1 spirometric endpoints as a measure of the anti-inflammatory and bronchodilatory effects of fluticasone/formoterol combination therapy JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P4131 VO 42 IS Suppl 57 A1 Sanjeeva Dissanayake A1 Birgit Grothe A1 Tammy McIver A1 Kirsten Kaiser YR 2013 UL http://erj.ersjournals.com/content/42/Suppl_57/P4131.abstract AB Background: The change from pre-dose FEV1 at day 1 to 2-hours post-dose FEV1 at week 12 was used as a co-primary spirometric outcome in the development of fluticasone/formoterol combination therapy (FLUT/FORM; flutiform®) in the pivotal studies. As this endpoint is not well characterised in the literature, we investigated its utility by examining the relationship with other spirometric and non-spirometric indices, including the change from pre-dose FEV1 at day 1 to pre-dose FEV1 at week 12 and FEV1 AUC0-12 at week 12 (area under the FEV1 curve over 0-12 hrs post-dose at week 12).Methods: FEV1 and AUC endpoint data from 3 randomised, double-blind, 12-week studies comparing FLUT/FORM pMDI to fluticasone pMDI were pooled, and Pearson’s correlation coefficient (R) or odds ratios were calculated.Results and Conclusions: Change from pre-dose FEV1 at day 1 to 2h post-dose FEV1 at week 12 assesses both chronic ICS-mediated anti-inflammatory and acute LABA bronchodilatory effects. This endpoint correlated well with the pre-dose FEV1 (R=0.86) and FEV1 AUC0-12 (R=0.96) endpoints. Pre dose FEV1 and 2h post-dose FEV1 were similarly predictive of subsequent exacerbation risk. Both endpoints also exhibited similar correlations with other endpoints, e.g., asthma control days. These data indicate that 2h post-dose FEV1 is a useful surrogate for FEV1 AUC0-12 in ICS-LABA vs ICS studies, and allows similar conclusions to be drawn as with pre-dose FEV1. Given greater treatment differences vs ICS, change from pre-dose FEV1 at day 1 to 2h post-dose FEV1 allows sample size savings in such studies if used as a primary endpoint instead of pre-dose FEV1.