Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Spirometry was conducted according to internationally accepted standards. Trough FEV1 is defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings measured at day 29, after 28 days of treatment. Mixed model: Trough FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.

Time frame: Day 29

Population: The Per Protocol Set includes the Full analysis Set patients with available data and without any major protocol deviations or criteria causing exclusion.~Patients were analyzed according to the treatment to which they were randomized.

The mean total symptom scores and mean individual symptom scores for the patient were calculated for the whole study period. The mean change from baseline in the total scores and in the individual scores were summarized by treatment and were analyzed for the percentage of 'nights with no nighttime awakenings'. The symptom variables for the whole active treatment period was analyzed using the similar MIXED model as for the primary endpoint, with the baseline FEV1 term being replaced by the respective baseline symptom variables.

Time frame: 28 days

Population: The Modified per protocol set (PPS) was defined post-DBL and included all patients with available data and without any major protocol deviations or criteria or GCP finding causing exclusion. Patients were analyzed according to the treatment to which they were randomized.

The number of puffs of rescue medication taken in the previous 12 hours was recorded in the Patient Diary in the morning and evening. The total number of puffs of rescue medication per day over the whole active treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening) then a half day was used in the denominator.

Time frame: Baseline and 28 days

Population: The Per Protocol Set includes the Full analysis Set patients with available data and without any major protocol deviations or criteria causing exclusion.~Patients were analyzed according to the treatment to which they were randomized.

Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.

Time frame: 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 1

Population: The Per Protocol Set includes the Full analysis Set patients with available data and without any major protocol deviations or criteria causing exclusion.~Patients were analyzed according to the treatment to which they were randomized.

Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 28 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.

Time frame: 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 28

Population: The Per Protocol Set includes the Full analysis Set patients with available data and without any major protocol deviations or criteria causing exclusion.~Patients were analyzed according to the treatment to which they were randomized.

Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.

Time frame: 5 min - 4 hr at Days 1 and 28

Population: The Per Protocol Set includes the Full analysis Set patients with available data and without any major protocol deviations or criteria causing exclusion.~Patients were analyzed according to the treatment to which they were randomized.

Time course of Forced Expiratory Volume in 1 second (FEV1) was measured at -45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.

Time frame: -45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28

Population: The Per Protocol Set includes the Full analysis Set patients with available data and without any major protocol deviations or criteria causing exclusion. Patients were analyzed according to the treatment to which they were randomized.