Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
This primary objective of this study is to compare two doses of BI 1744 CL inhalation solution delivered by the Respimat® inhaler once daily to placebo in patients with chronic obstructive pulmonary disease (COPD). The safety of BI 1744 CL inhalation solution delivered through the Respimat inhaler will also be compared to placebo.
Interventions
Comparison of low and high doses on efficacy and safety in COPD patients
DRUGplacebo
Olodaterol (BI1744) placebo inhaled orally once daily from the Respimat inhaler
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients must have a diagnosis of chronic obstructive pulmonary disease * Male or female patients, 40 years of age or older Patients must be current or ex-smokers with a smoking history of more than 10 pack years Post bronchodilator FEV1 \<80% predicted and post-bronchodilator FEV1/FVC \<70%
Exclusion criteria
* Patients with a significant disease other than COPD * Patients with a history of asthma * Patients with any of the following conditions: a history of myocardial infarction within 1 year of screening visit (Visit 1) unstable or life-threatening cardiac arrhythmia. have been hospitalized for heart failure within the past year. known active tuberculosis a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed) a history of life-threatening pulmonary obstruction a history of cystic fibrosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks) | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Day 85 | Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. |
| Trough FEV1 Response at Day 85 (12 Weeks) | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h and - 10 mins prior to study drug at Day 85. | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks | Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. |
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -1h, -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks | Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. |
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks | Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. |
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks | Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. |
| Trough FEV1 Response After 2 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 2 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed a -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FEV1 Response After 6 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 6 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FEV1 Response After 18 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 18 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FEV1 Response After 24 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 24 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FEV1 Response After 32 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 32 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FEV1 Response After 40 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 40 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FEV1 Response After 48 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 48 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Peak FEV1 (0-3h) Response At Day 1 | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1 | Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by- visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Peak FEV1 (0-3h) Response After 2 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks | Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Peak FEV1 (0-3h) Response After 6 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks | Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Peak FEV1 (0-3h) Response After 12 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks | Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Peak FEV1 (0-3h) Response After 24 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks | Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Peak FEV1 (0-3h) Response After 48 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks | Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1 | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1 | Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks | Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks | Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks | Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks | Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks | Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| Trough FVC Response After 2 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 2 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FVC Response After 6 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 6 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FVC Response After 12 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 12 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FVC Response After 18 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 18 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FVC Response After 24 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 24 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FVC Response After 32 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 32 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FVC Response After 40 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 40 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Trough FVC Response After 48 Weeks | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 48 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| FVC Peak (0-3h) Response At Day 1 | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1 | Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| FVC Peak (0-3h) Response After 2 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks | Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| FVC Peak (0-3h) Response After 6 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks | Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| FVC Peak (0-3h) Response After 12 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks | Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| FVC Peak (0-3h) Response After 24 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks | Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| FVC Peak (0-3h) Response After 48 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks | Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. |
| Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks) | 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks) | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FVC AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. |
| Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF) | immediately upon arising (before drug administration) from Screening to week 48 | Weekly mean pre-dose morning peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded. |
| Weekly Mean Evening Peak Expiratory Flow Rate (PEF) | at bedtime from Screening to week 48 | Weekly mean evening peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded. |
| Weekly Mean Daytime Rescue Use | From Screening to week 48 | The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. |
| Weekly Mean Nighttime Rescue Use | From Screening to week 48 | The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. |
| Weekly Mean Daily (24h) Rescue Use | From Screening to week 48 | The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. |
| Patient's Global Rating at Week 6 | Week 6 visit | Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. |
| Patient's Global Rating at Week 12 | Week 12 visit | Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. |
| Patient's Global Rating at Week 24 | Week 24 visit | Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. |
| Patient's Global Rating at Week 48 | Week 48 visit | Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. |
| Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Baseline to end of study at 48 weeks. | Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile. |
| Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | Baseline to end of study at 48 weeks. | Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile. |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks) | 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks) | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. |
| Number of COPD Exacerbations | Baseline to end of study at week 48 visit | Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. |
| Number of COPD Exacerbations Requiring Hospitalization | Baseline to end of study at week 48 visit | Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. |
| Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | Baseline to end of study at 48 weeks. | Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. |
| Changes in Safety Parameters Related to Treatment | 48 weeks | Occurrence of bronchoconstriction, cardiac disorders and investigations related to treatment. Bronchoconstriction is defined as any of the following events: Drop in trough FEV1 \>= 15%, Rescue medication use within 30 min of inhaling randomized treatment on a clinic test day or Cough, wheeze, or dyspnoea AE within 30 min of inhaling randomized treatment on a clinic test day. |
| Change From Baseline in Potassium | Day 1 and at 12, 24 and 48 weeks | Laboratory testing: Average change from baseline of potassium measured. The laboratory tests at Day 1 were considered the baseline measurements. |
| Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Baseline to end of study at 48 weeks. | Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile. |
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1 | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at day 1 | Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. |
Countries
Australia, China, Germany, New Zealand, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Placebo delivered by the Respimat Inhaler. | 209 |
| Olo 5 mcg qd Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler. | 208 |
| Olo 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler. | 207 |
| Total | 624 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 21 | 17 | 16 |
| Overall Study | Lack of Efficacy | 13 | 4 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 | 2 |
| Overall Study | Non compliance with protocol | 0 | 3 | 2 |
| Overall Study | Other reason not described above | 3 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 11 | 8 | 11 |
Baseline characteristics
| Characteristic | Placebo | Olo 5 mcg qd | Olo 10 mcg qd | Total |
|---|---|---|---|---|
| Age, Continuous | 65.8 years STANDARD_DEVIATION 8.5 | 64.0 years STANDARD_DEVIATION 8.6 | 65.0 years STANDARD_DEVIATION 8.2 | 64.9 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 57 Participants | 58 Participants | 52 Participants | 167 Participants |
| Sex: Female, Male Male | 152 Participants | 150 Participants | 155 Participants | 457 Participants |
| Tiotropium (Tio) Use Stratum Non-tiotropium | 160 Number of participants | 161 Number of participants | 156 Number of participants | 477 Number of participants |
| Tiotropium (Tio) Use Stratum Tiotropium | 49 Number of participants | 47 Number of participants | 51 Number of participants | 147 Number of participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 93 / 209 | 83 / 208 | 78 / 207 |
| serious Total, serious adverse events | 34 / 209 | 39 / 208 | 43 / 207 |
Outcome results
Primary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Day 85
Population: Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before Day 85 (12 weeks) for either co-primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks) | -0.007 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks) | 0.165 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks) | 0.169 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.135, 0.209]Mixed Models Analysis
p-value: <0.000195% CI: [0.139, 0.214]Mixed Models Analysis
Primary
Trough FEV1 Response at Day 85 (12 Weeks)
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h and - 10 mins prior to study drug at Day 85.
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Day 85 (12 Weeks) | -0.041 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Trough FEV1 Response at Day 85 (12 Weeks) | 0.050 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response at Day 85 (12 Weeks) | 0.060 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.054, 0.128]Mixed Models Analysis
p-value: <0.000195% CI: [0.064, 0.137]Mixed Models Analysis
Secondary
Change From Baseline in Potassium
Laboratory testing: Average change from baseline of potassium measured. The laboratory tests at Day 1 were considered the baseline measurements.
Time frame: Day 1 and at 12, 24 and 48 weeks
Population: Treated set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Potassium | 0.0 mmol/L | Standard Deviation 0.4 |
| Olo 5 mcg qd | Change From Baseline in Potassium | 0.0 mmol/L | Standard Deviation 0.3 |
| Olo 10 mcg qd | Change From Baseline in Potassium | 0.0 mmol/L | Standard Deviation 0.3 |
Secondary
Changes in Safety Parameters Related to Treatment
Occurrence of bronchoconstriction, cardiac disorders and investigations related to treatment. Bronchoconstriction is defined as any of the following events: Drop in trough FEV1 \>= 15%, Rescue medication use within 30 min of inhaling randomized treatment on a clinic test day or Cough, wheeze, or dyspnoea AE within 30 min of inhaling randomized treatment on a clinic test day.
Time frame: 48 weeks
Population: Treated set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Changes in Safety Parameters Related to Treatment | Ventricular extrasystoles | 0.0 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Electrocardiogram QT prolonged | 0.5 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Bronchoconstriction | 13.4 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Atrial fibrillation | 0.0 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Angina pectoris | 0.0 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Forced expiratory volume decreased | 0.0 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Ventricular extrasystoles | 0.5 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Forced expiratory volume decreased | 0.0 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Angina pectoris | 0.5 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Electrocardiogram QT prolonged | 0.5 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Bronchoconstriction | 2.4 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Atrial fibrillation | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Bronchoconstriction | 3.9 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Atrial fibrillation | 1.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Angina pectoris | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Ventricular extrasystoles | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Forced expiratory volume decreased | 0.5 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Electrocardiogram QT prolonged | 0.0 percentage of participants |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)
Population: Patients in FAS with spirometry data after 3 hours at Visit 5 (12-hour pulmonary function test set)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks) | -0.029 Liter | Standard Error 0.025 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks) | 0.144 Liter | Standard Error 0.022 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks) | 0.139 Liter | Standard Error 0.022 |
p-value: <0.000195% CI: [0.113, 0.233]ANCOVA
p-value: <0.000195% CI: [0.108, 0.229]Mixed Models Analysis
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks | -0.18 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks | 0.156 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks | 0.143 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.136, 0.212]Mixed Models Analysis
p-value: <0.000195% CI: [0.123, 0.199]Mixed Models Analysis
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks | -0.000 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks | 0.180 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks | 0.192 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.144, 0.217]Mixed Models Analysis
p-value: <0.000195% CI: [0.156, 0.229]Mixed Models Analysis
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks | -0.043 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks | 0.130 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks | 0.126 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.134, 0.211]Mixed Models Analysis
p-value: <0.000195% CI: [0.131, 0.208]Mixed Models Analysis
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -1h, -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks | -0.001 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks | 0.169 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks | 0.165 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.133, 0.207]Mixed Models Analysis
p-value: <0.000195% CI: [0.13, 0.204]Mixed Models Analysis
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at day 1
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1 | 0.024 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1 | 0.189 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1 | 0.199 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.128, 0.201]Mixed Models Analysis
p-value: <0.000195% CI: [0.139, 0.212]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FVC AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)
Population: Patients in FAS with spirometry data after 3 hours at Visit 5 (12-hour pulmonary function test set)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks) | -0.019 Liter | Standard Error 0.049 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks) | 0.283 Liter | Standard Error 0.045 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks) | 0.230 Liter | Standard Error 0.044 |
p-value: <0.000195% CI: [0.181, 0.422]ANCOVA
p-value: <0.000195% CI: [0.128, 0.37]ANCOVA
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks
Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks | 0.026 Liter | Standard Error 0.027 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks | 0.323 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks | 0.353 Liter | Standard Error 0.027 |
p-value: <0.000195% CI: [0.224, 0.368]Mixed Models Analysis
p-value: <0.000195% CI: [0.255, 0.399]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1
Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1 | 0.063 Liter | Standard Error 0.027 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1 | 0.350 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1 | 0.392 Liter | Standard Error 0.027 |
p-value: <0.000195% CI: [0.216, 0.359]Mixed Models Analysis
p-value: <0.000195% CI: [0.258, 0.401]Mixed Models Analysis
Secondary
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks
Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks | 0.003 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks | 0.277 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks | 0.295 Liter | Standard Error 0.028 |
p-value: <0.000195% CI: [0.201, 0.348]Mixed Models Analysis
p-value: <0.000195% CI: [0.219, 0.366]Mixed Models Analysis
Secondary
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks
Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks | 0.026 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks | 0.261 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks | 0.281 Liter | Standard Error 0.028 |
p-value: <0.000195% CI: [0.161, 0.309]Mixed Models Analysis
p-value: <0.000195% CI: [0.18, 0.329]Mixed Models Analysis
Secondary
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks
Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks | -0.040 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks | 0.204 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks | 0.231 Liter | Standard Error 0.028 |
p-value: <0.000195% CI: [0.169, 0.319]Mixed Models Analysis
p-value: <0.000195% CI: [0.196, 0.346]Mixed Models Analysis
Secondary
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks
Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks | 0.022 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks | 0.276 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks | 0.316 Liter | Standard Error 0.027 |
p-value: <0.000195% CI: [0.181, 0.327]Mixed Models Analysis
p-value: <0.000195% CI: [0.22, 0.366]Mixed Models Analysis
Secondary
FVC Peak (0-3h) Response After 12 Weeks
Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Peak (0-3h) Response After 12 Weeks | 0.169 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | FVC Peak (0-3h) Response After 12 Weeks | 0.421 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | FVC Peak (0-3h) Response After 12 Weeks | 0.430 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.174, 0.329]Mixed Models Analysis
p-value: <0.000195% CI: [0.183, 0.338]Mixed Models Analysis
Secondary
FVC Peak (0-3h) Response After 24 Weeks
Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Peak (0-3h) Response After 24 Weeks | 0.188 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | FVC Peak (0-3h) Response After 24 Weeks | 0.419 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | FVC Peak (0-3h) Response After 24 Weeks | 0.420 Liter | Standard Error 0.03 |
p-value: <0.000195% CI: [0.153, 0.31]Mixed Models Analysis
p-value: <0.000195% CI: [0.154, 0.311]Mixed Models Analysis
Secondary
FVC Peak (0-3h) Response After 2 Weeks
Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Peak (0-3h) Response After 2 Weeks | 0.207 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | FVC Peak (0-3h) Response After 2 Weeks | 0.471 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | FVC Peak (0-3h) Response After 2 Weeks | 0.499 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.188, 0.341]Mixed Models Analysis
p-value: <0.000195% CI: [0.216, 0.368]Mixed Models Analysis
Secondary
FVC Peak (0-3h) Response After 48 Weeks
Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Peak (0-3h) Response After 48 Weeks | 0.109 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | FVC Peak (0-3h) Response After 48 Weeks | 0.356 Liter | Standard Error 0.03 |
| Olo 10 mcg qd | FVC Peak (0-3h) Response After 48 Weeks | 0.369 Liter | Standard Error 0.03 |
p-value: <0.000195% CI: [0.168, 0.327]Mixed Models Analysis
p-value: <0.000195% CI: [0.181, 0.34]Mixed Models Analysis
Secondary
FVC Peak (0-3h) Response After 6 Weeks
Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Peak (0-3h) Response After 6 Weeks | 0.180 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | FVC Peak (0-3h) Response After 6 Weeks | 0.430 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | FVC Peak (0-3h) Response After 6 Weeks | 0.460 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.174, 0.328]Mixed Models Analysis
p-value: <0.000195% CI: [0.203, 0.358]Mixed Models Analysis
Secondary
FVC Peak (0-3h) Response At Day 1
Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Peak (0-3h) Response At Day 1 | 0.245 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | FVC Peak (0-3h) Response At Day 1 | 0.509 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | FVC Peak (0-3h) Response At Day 1 | 0.546 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.187, 0.339]Mixed Models Analysis
p-value: <0.000195% CI: [0.225, 0.376]Mixed Models Analysis
Secondary
Number of COPD Exacerbations
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria.
Time frame: Baseline to end of study at week 48 visit
Population: Treated set- all patients who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of COPD Exacerbations | 0.7476 Number of COPD exacerbations | Standard Error 0.0972 |
| Olo 5 mcg qd | Number of COPD Exacerbations | 0.5842 Number of COPD exacerbations | Standard Error 0.0791 |
| Olo 10 mcg qd | Number of COPD Exacerbations | 0.6322 Number of COPD exacerbations | Standard Error 0.0822 |
p-value: 0.163195% CI: [0.5524, 1.1054]Negative binomial regression
p-value: 0.334295% CI: [0.6015, 1.1889]Negative binomial regression
Secondary
Number of COPD Exacerbations Requiring Hospitalization
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization.
Time frame: Baseline to end of study at week 48 visit
Population: Treated set- all patients who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of COPD Exacerbations Requiring Hospitalization | 0.1010 Number of COPD exacerbations | Standard Error 0.0314 |
| Olo 5 mcg qd | Number of COPD Exacerbations Requiring Hospitalization | 0.0662 Number of COPD exacerbations | Standard Error 0.0224 |
| Olo 10 mcg qd | Number of COPD Exacerbations Requiring Hospitalization | 0.1133 Number of COPD exacerbations | Standard Error 0.0319 |
p-value: 0.298595% CI: [0.2947, 1.4556]Negative binomial regression
p-value: 0.75595% CI: [0.5464, 2.3003]Negative binomial regression
Secondary
Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids.
Time frame: Baseline to end of study at 48 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | 0.5745 Number of COPD exacerbations | Standard Error 0.0844 |
| Olo 5 mcg qd | Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | 0.4643 Number of COPD exacerbations | Standard Error 0.0714 |
| Olo 10 mcg qd | Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | 0.4875 Number of COPD exacerbations | Standard Error 0.0723 |
p-value: 0.291195% CI: [0.5438, 1.2008]Negative binomial regression
p-value: 0.408695% CI: [0.5743, 1.2535]Negative binomial regression
Secondary
Patient's Global Rating at Week 12
Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.
Time frame: Week 12 visit
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient's Global Rating at Week 12 | 3.4 Point on scale | Standard Error 0.1 |
| Olo 5 mcg qd | Patient's Global Rating at Week 12 | 3.0 Point on scale | Standard Error 0.1 |
| Olo 10 mcg qd | Patient's Global Rating at Week 12 | 3.0 Point on scale | Standard Error 0.1 |
p-value: <0.000195% CI: [-0.7, -0.2]Mixed Models Analysis
p-value: <0.000195% CI: [-0.6, -0.2]Mixed Models Analysis
Secondary
Patient's Global Rating at Week 24
Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.
Time frame: Week 24 visit
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient's Global Rating at Week 24 | 3.5 Point on scale | Standard Error 0.1 |
| Olo 5 mcg qd | Patient's Global Rating at Week 24 | 3.0 Point on scale | Standard Error 0.1 |
| Olo 10 mcg qd | Patient's Global Rating at Week 24 | 3.0 Point on scale | Standard Error 0.1 |
p-value: <0.000195% CI: [-0.7, -0.2]Mixed Models Analysis
p-value: <0.000195% CI: [-0.7, -0.2]Mixed Models Analysis
Secondary
Patient's Global Rating at Week 48
Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.
Time frame: Week 48 visit
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient's Global Rating at Week 48 | 3.4 Point on scale | Standard Error 0.1 |
| Olo 5 mcg qd | Patient's Global Rating at Week 48 | 3.1 Point on scale | Standard Error 0.1 |
| Olo 10 mcg qd | Patient's Global Rating at Week 48 | 3.1 Point on scale | Standard Error 0.1 |
p-value: 0.010995% CI: [-0.5, -0.1]Mixed Models Analysis
p-value: 0.003195% CI: [-0.6, -0.1]Mixed Models Analysis
Secondary
Patient's Global Rating at Week 6
Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.
Time frame: Week 6 visit
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient's Global Rating at Week 6 | 3.5 Point on scale | Standard Error 0.1 |
| Olo 5 mcg qd | Patient's Global Rating at Week 6 | 3.0 Point on scale | Standard Error 0.1 |
| Olo 10 mcg qd | Patient's Global Rating at Week 6 | 3.0 Point on scale | Standard Error 0.1 |
p-value: <0.000195% CI: [-0.7, -0.3]Mixed Models Analysis
p-value: <0.000195% CI: [-0.7, -0.3]Mixed Models Analysis
Secondary
Peak FEV1 (0-3h) Response After 12 Weeks
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 12 Weeks | 0.071 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 12 Weeks | 0.235 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 12 Weeks | 0.236 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.123, 0.204]Mixed Models Analysis
p-value: <0.000195% CI: [0.124, 0.206]Mixed Models Analysis
Secondary
Peak FEV1 (0-3h) Response After 24 Weeks
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 24 Weeks | 0.055 Liter | Standard Error 0.016 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 24 Weeks | 0.230 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 24 Weeks | 0.206 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.134, 0.216]Mixed Models Analysis
p-value: <0.000195% CI: [0.11, 0.192]Mixed Models Analysis
Secondary
Peak FEV1 (0-3h) Response After 2 Weeks
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 2 Weeks | 0.077 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.254 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.267 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.137, 0.217]Mixed Models Analysis
p-value: <0.000195% CI: [0.15, 0.23]Mixed Models Analysis
Secondary
Peak FEV1 (0-3h) Response After 48 Weeks
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 48 Weeks | 0.029 Liter | Standard Error 0.016 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 48 Weeks | 0.198 Liter | Standard Error 0.016 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 48 Weeks | 0.192 Liter | Standard Error 0.016 |
p-value: <0.000195% CI: [0.128, 0.211]Mixed Models Analysis
p-value: <0.000195% CI: [0.121, 0.205]Mixed Models Analysis
Secondary
Peak FEV1 (0-3h) Response After 6 Weeks
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 6 Weeks | 0.066 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 6 Weeks | 0.238 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 6 Weeks | 0.238 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.132, 0.212]Mixed Models Analysis
p-value: <0.000195% CI: [0.132, 0.212]Mixed Models Analysis
Secondary
Peak FEV1 (0-3h) Response At Day 1
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by- visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response At Day 1 | 0.104 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.259 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.275 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.115, 0.194]Mixed Models Analysis
p-value: <0.000195% CI: [0.131, 0.211]Mixed Models Analysis
Secondary
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.
Time frame: Baseline to end of study at 48 weeks.
Population: Treated set- all patients who received at least one dose of study medication
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 194.0 days |
| Olo 5 mcg qd | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 160.0 days |
| Olo 10 mcg qd | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 203.0 days |
| Olo 5 mcg qd (Non-tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 236.0 days |
| Olo 10 mcg qd (Tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 167.0 days |
| Olo 10 mcg qd(Non-tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 239.0 days |
p-value: 0.065895% CI: [0.522, 1.016]Regression, Cox
p-value: 0.170195% CI: [0.576, 1.107]Regression, Cox
Secondary
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.
Time frame: Baseline to end of study at 48 weeks.
Population: Treated set- all patients who received at least one dose of study medication
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | NA days |
| Olo 5 mcg qd | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | NA days |
| Olo 10 mcg qd | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | NA days |
| Olo 5 mcg qd (Non-tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | NA days |
| Olo 10 mcg qd (Tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | NA days |
| Olo 10 mcg qd(Non-tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | NA days |
p-value: 0.275495% CI: [0.313, 1.374]Regression, Cox
p-value: 0.979295% CI: [0.521, 1.961]Regression, Cox
Secondary
Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.
Time frame: Baseline to end of study at 48 weeks.
Population: Treated set- all patients who received at least one dose of study medication
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 194.0 days |
| Olo 5 mcg qd | Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 216.0 days |
| Olo 10 mcg qd | Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 218.0 days |
| Olo 5 mcg qd (Non-tiotropium) | Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 344.0 days |
| Olo 10 mcg qd (Tiotropium) | Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 170.0 days |
| Olo 10 mcg qd(Non-tiotropium) | Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 309.0 days |
p-value: 0.119495% CI: [0.506, 1.078]Regression, Cox
p-value: 0.25795% CI: [0.561, 1.174]Regression, Cox
Secondary
Trough FEV1 Response After 18 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 18 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 18 Weeks | -0.042 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Trough FEV1 Response After 18 Weeks | 0.056 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response After 18 Weeks | 0.059 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.061, 0.135]Mixed Models Analysis
p-value: <0.000195% CI: [0.064, 0.138]Mixed Models Analysis
Secondary
Trough FEV1 Response After 24 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 24 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 24 Weeks | -0.050 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Trough FEV1 Response After 24 Weeks | 0.036 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response After 24 Weeks | 0.039 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.049, 0.123]Mixed Models Analysis
p-value: <0.000195% CI: [0.051, 0.126]Mixed Models Analysis
Secondary
Trough FEV1 Response After 2 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed a -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 2 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 2 Weeks | -0.019 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Trough FEV1 Response After 2 Weeks | 0.076 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response After 2 Weeks | 0.091 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.059, 0.131]Mixed Models Analysis
p-value: <0.000195% CI: [0.075, 0.147]Mixed Models Analysis
Secondary
Trough FEV1 Response After 32 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 32 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 32 Weeks | -0.051 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Trough FEV1 Response After 32 Weeks | 0.041 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response After 32 Weeks | 0.034 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.054, 0.13]Mixed Models Analysis
p-value: <0.000195% CI: [0.048, 0.123]Mixed Models Analysis
Secondary
Trough FEV1 Response After 40 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 40 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 40 Weeks | -0.061 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Trough FEV1 Response After 40 Weeks | 0.046 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response After 40 Weeks | 0.044 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.069, 0.145]Mixed Models Analysis
p-value: <0.000195% CI: [0.068, 0.143]Mixed Models Analysis
Secondary
Trough FEV1 Response After 48 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 48 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 48 Weeks | -0.74 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Trough FEV1 Response After 48 Weeks | 0.019 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response After 48 Weeks | 0.017 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.055, 0.13]Mixed Models Analysis
p-value: <0.000195% CI: [0.053, 0.129]Mixed Models Analysis
Secondary
Trough FEV1 Response After 6 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 6 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 6 Weeks | -0.022 Liter | Standard Error 0.014 |
| Olo 5 mcg qd | Trough FEV1 Response After 6 Weeks | 0.073 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response After 6 Weeks | 0.069 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.059, 0.131]Mixed Models Analysis
p-value: <0.000195% CI: [0.054, 0.127]Mixed Models Analysis
Secondary
Trough FVC Response After 12 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 12 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 12 Weeks | -0.030 Liter | Standard Error 0.027 |
| Olo 5 mcg qd | Trough FVC Response After 12 Weeks | 0.085 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Trough FVC Response After 12 Weeks | 0.130 Liter | Standard Error 0.027 |
p-value: 0.001995% CI: [0.043, 0.187]Mixed Models Analysis
p-value: <0.000195% CI: [0.088, 0.233]Mixed Models Analysis
Secondary
Trough FVC Response After 18 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 18 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 18 Weeks | -0.028 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Trough FVC Response After 18 Weeks | 0.102 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Trough FVC Response After 18 Weeks | 0.134 Liter | Standard Error 0.027 |
p-value: 0.000595% CI: [0.057, 0.203]Mixed Models Analysis
p-value: <0.000195% CI: [0.089, 0.235]Mixed Models Analysis
Secondary
Trough FVC Response After 24 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 24 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 24 Weeks | -0.028 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Trough FVC Response After 24 Weeks | 0.055 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Trough FVC Response After 24 Weeks | 0.096 Liter | Standard Error 0.027 |
p-value: 0.026195% CI: [0.01, 0.156]Mixed Models Analysis
p-value: 0.00195% CI: [0.05, 0.197]Mixed Models Analysis
Secondary
Trough FVC Response After 2 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 2 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 2 Weeks | -0.015 Liter | Standard Error 0.027 |
| Olo 5 mcg qd | Trough FVC Response After 2 Weeks | 0.132 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Trough FVC Response After 2 Weeks | 0.169 Liter | Standard Error 0.027 |
p-value: <0.000195% CI: [0.076, 0.218]Mixed Models Analysis
p-value: <0.000195% CI: [0.113, 0.255]Mixed Models Analysis
Secondary
Trough FVC Response After 32 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 32 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 32 Weeks | -0.026 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Trough FVC Response After 32 Weeks | 0.065 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response After 32 Weeks | 0.097 Liter | Standard Error 0.027 |
p-value: 0.015495% CI: [0.018, 0.165]Mixed Models Analysis
p-value: 0.001195% CI: [0.049, 0.197]Mixed Models Analysis
Secondary
Trough FVC Response After 40 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 40 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 40 Weeks | -0.044 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Trough FVC Response After 40 Weeks | 0.087 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response After 40 Weeks | 0.111 Liter | Standard Error 0.028 |
p-value: 0.000695% CI: [0.057, 0.205]Mixed Models Analysis
p-value: <0.000195% CI: [0.08, 0.229]Mixed Models Analysis
Secondary
Trough FVC Response After 48 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 48 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 48 Weeks | -0.083 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Trough FVC Response After 48 Weeks | 0.011 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response After 48 Weeks | 0.032 Liter | Standard Error 0.028 |
p-value: 0.013495% CI: [0.019, 0.168]Mixed Models Analysis
p-value: 0.002595% CI: [0.04, 0.19]Mixed Models Analysis
Secondary
Trough FVC Response After 6 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 6 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 6 Weeks | -0.005 Liter | Standard Error 0.027 |
| Olo 5 mcg qd | Trough FVC Response After 6 Weeks | 0.125 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Trough FVC Response After 6 Weeks | 0.135 Liter | Standard Error 0.027 |
p-value: 0.000395% CI: [0.059, 0.203]Mixed Models Analysis
p-value: 0.000195% CI: [0.069, 0.213]Mixed Models Analysis
Secondary
Weekly Mean Daily (24h) Rescue Use
The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.
Time frame: From Screening to week 48
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weekly Mean Daily (24h) Rescue Use | 3.747 Number of puffs | Standard Error 0.265 |
| Olo 5 mcg qd | Weekly Mean Daily (24h) Rescue Use | 2.642 Number of puffs | Standard Error 0.267 |
| Olo 10 mcg qd | Weekly Mean Daily (24h) Rescue Use | 2.312 Number of puffs | Standard Error 0.265 |
p-value: 0.001995% CI: [-1.799, -0.409]ANCOVA
p-value: <0.000195% CI: [-2.13, -0.74]ANCOVA
Secondary
Weekly Mean Daytime Rescue Use
The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.
Time frame: From Screening to week 48
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weekly Mean Daytime Rescue Use | 1.487 Number of puffs | Standard Error 0.136 |
| Olo 5 mcg qd | Weekly Mean Daytime Rescue Use | 0.967 Number of puffs | Standard Error 0.137 |
| Olo 10 mcg qd | Weekly Mean Daytime Rescue Use | 0.839 Number of puffs | Standard Error 0.136 |
p-value: 0.004595% CI: [-0.878, -0.162]ANCOVA
p-value: 0.000495% CI: [-1.005, -0.291]ANCOVA
Secondary
Weekly Mean Evening Peak Expiratory Flow Rate (PEF)
Weekly mean evening peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded.
Time frame: at bedtime from Screening to week 48
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weekly Mean Evening Peak Expiratory Flow Rate (PEF) | 190.676 L/min | Standard Error 3.165 |
| Olo 5 mcg qd | Weekly Mean Evening Peak Expiratory Flow Rate (PEF) | 207.862 L/min | Standard Error 3.202 |
| Olo 10 mcg qd | Weekly Mean Evening Peak Expiratory Flow Rate (PEF) | 205.236 L/min | Standard Error 3.166 |
p-value: <0.000195% CI: [8.849, 25.523]ANCOVA
p-value: 0.000695% CI: [6.259, 22.86]ANCOVA
Secondary
Weekly Mean Nighttime Rescue Use
The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.
Time frame: From Screening to week 48
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weekly Mean Nighttime Rescue Use | 2.283 Number of puffs | Standard Error 0.151 |
| Olo 5 mcg qd | Weekly Mean Nighttime Rescue Use | 1.701 Number of puffs | Standard Error 0.152 |
| Olo 10 mcg qd | Weekly Mean Nighttime Rescue Use | 1.492 Number of puffs | Standard Error 0.152 |
p-value: 0.004195% CI: [-0.979, -0.185]ANCOVA
p-value: 0.000195% CI: [-1.189, -0.394]ANCOVA
Secondary
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)
Weekly mean pre-dose morning peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded.
Time frame: immediately upon arising (before drug administration) from Screening to week 48
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF) | 180.019 L/min | Standard Error 3.182 |
| Olo 5 mcg qd | Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF) | 193.376 L/min | Standard Error 3.207 |
| Olo 10 mcg qd | Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF) | 195.475 L/min | Standard Error 3.184 |
p-value: 0.001895% CI: [5.005, 21.709]ANCOVA
p-value: 0.000395% CI: [7.114, 23.8]ANCOVA