Evaluation of Umeclidinium Bromide in Combination With Fluticasone Furoate in COPD Subjects With an Asthmatic Component

All participants received the albuterol/salbutamol via MDI as a rescue medication on an as-needed basis. Total daily rescue medication use for a given day is the sum of daytime albuterol/salbutamol use recorded in PM and nighttime albuterol/salbutamol use recorded in AM the next day. The number of puffs of albuterol (salbutamol) MDI used in the last 12 hours for relief of symptoms were recorded morning and evening in the eDiary by the participants. End of Treatment Phase A is the last 7 days of Treatment Phase A. Change from Baseline at the end of Treatment Phase is the difference between the end of Treatment Phase value and the appropriate baseline week. Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline rescue medication use, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization

A daily symptoms score for exacerbations of chronic pulmonary disease tool - Respiratory Symptoms (E-RS) is derived by summing the 11 item-level E-RS scores and has a theoretical range of 0-40, with higher values indicating more severe respiratory symptoms. The Baseline E-RS score is defined as the mean within-subject daily score over the 7 days prior to randomization, with data present for a minimum of 4 of the 7 days. Change from Baseline at the end of Treatment Phase is the difference between the end of Treatment Phase value and the appropriate Baseline week. Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline score, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization. All comparisons for statistical purposes are with the FF 100 µg arm.

Peak expiratory flow (PEF) stability limit was calculated from AM PEF measurements on the 7 days preceding Visit 3 as mean AM PEF from the available 7 days preceding Visit 3 x 80%. PEF stability limit serves as a benchmark of the participants run-in COPD status and used for comparison during the treatment phase to assess subject safety. Change from Baseline over the last 21 days of Treatment Phase A is the difference between the last 21 days of Treatment Phase A and the appropriate Baseline week. The last 21 days of Treatment Phase A include the AM assessments on the date of Visit 6. AM assessments include the date of Visit 6 and the 20 consecutive days preceding the date of Visit. Analysis performed using analysis of covariance with covariates of treatment, age, sex, Baseline AM PEF, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification. Baseline is the last 7 days of the run-in period prior to randomization

FEV1 was measured in the morning by spirometry. At Visit 5, after trough FEV1 is measured, subject received investigational product. 3 hours post-dose, spirometry was repeated and subject then received 2 puffs of albuterol/salbutamol. After 30 minutes,spirometry was repeated.. Change from Baseline in clinic trough (pre-dose) FEV1 is the difference in the trough value at 3 hours post-dose peak FEV1 and the Baseline value. If the trough value or the Baseline was missing, then change from Baseline was considered as missing. Baseline value of clinic FEV1 is the last acceptable/borderline acceptable (pre-dose) FEV1 value obtained prior to randomization (from Visit 3 pre-dose or from Visit 2 pre-bronchodilator). Analysis done using analysis of covariance with covariates of treatment, age, sex, baseline clinic trough FEV1, pre-dose trough FEV1 at Visit 5, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification.

FEV1 is defined as forced expiratory volume in one second and measured in the morning at Visits 1 through 8 between 6:00 and 11:00 electronically by spirometry. Reversibility was measured at Visit 1 and Visit 2 for study eligibility by change in clinic FEV1 within 20 to 60 minutes following 4 inhalations of albuterol/salbutamol and again measured 3 hours after dosing at Visit 5 by change in clinic FEV1 30 minutes following 2 inhalations of albuterol/salbutamol. Baseline value of clinic FEV1 is the last acceptable/borderline acceptable (pre-dose) FEV1 value obtained prior to randomization (either from Visit 3 pre-dose or from Visit 2 pre-bronchodilator). Analysis performed using analysis of covariance with covariates of treatment, age, sex, baseline clinic trough FEV1, pre-albuterol/salbutamol FEV1 at Visit 5, pack years smoked per randomization stratification and age when first treated with an inhaler per randomization stratification.