PGx6712: An Exploratory Study of the Effects of 2 Common Variants in ADRB2 on Anoro (GSK573719/GW642444) Efficacy in Chronic Obstructive Pulmonary Disease in Multiple Clinical Studies

Trial description: The primary objective of this study is to identify if selected genetic variants in the ADRB2 gene associated with umeclidinium bromide/vilanterol, umeclidinium bromide, or vilanterol efficacy. A secondary objective is to identify genetic associations with baseline reversibility status and baseline FEV1/FVC. The association of genetic markers in ADRB2, the gene that encodes the beta2-adrenergic receptor expressed on airway smooth muscle cells, with efficacy response will be tested in subjects from 17 clinical studies in patients with COPD. Genetic variants tested will include the two common variants rs1042713 (A/G; Gly16Arg), rs1042714 (G/C; Gln27Glu), and the rare variant rs1800888 (T/C; Thr164Ile). Endpoints will include change from baseline of trough FEV1, baseline reversibility, and baseline FEV1/FVC. The effects of covariates will be regressed out within each study group and each drug to get residuals followed by inverse normal transformation. For the primary analysis, the inverse normal transformed residuals will be pooled across study groups and across drugs to estimate genetic effects in patients treated with each drug-containing regimen. Three models will be investigated. The primary model will consider all potential covariates. In the second model, all potential covariates except reversibility related covariates will be considered. In the third model, only basic covariates will be considered by excluding reversibility and baseline disease characteristics. To control family wise error rate, the per-marker significant level will be 0.17 after adjusting for multiple markers.ANORO is a trademark of the GlaxoSmithKline group of companies.