Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The primary objective of this study is to assess the long-term efficacy and safety of once daily treatment of BI 1744 CL inhalation solution (5 and 10 mcg) delivered via the Respimat® inhaler, in patients with COPD.
Interventions
Comparison of low and high doses on efficacy and safety in COPD patients
DRUGFormoterol
Active comparator with Olodaterol (BI 1744) on safety and efficacy in COPD patients
DRUGPlacebo
Placebo for comparison with Olodaterol (BI 1744) on safety and efficacy in COPD patients
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
1. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:post-bronchodilator FEV1\<80% of predicted normal (ECSC) and a post-bronchodilator FEV1/FVC \<70% at Visit 1 2. Male or female patients, 40 years of age or older 3. Patients must be current or ex-smokers with a smoking history of more than 10 pack years:
Exclusion criteria
1. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT \>x2 ULN, SGPT \>x2 ULN, bilirubin \>x2 ULN or creatinine \>x2 ULN 2. Patients with a history of asthma and/or total blood eosinophil count greater than 600/mm3 3. Patients with thyrotoxicosis, paroxysmal tachycardia (\>100 beats per minute) 4. Patients with a history of myocardial infarction within 1 year of screening visit, unstable or life-threatening cardiac arrhythmia, hospitalization 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, life-threatening pulmonary obstruction, cystic fibrosis, clinically evident bronchiectasis, significant alcohol or drug abuse 5. Patients who have undergone thoracotomy with pulmonary resection 6. Patients being treated with oral beta-adrenergics or oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day. 7. Patients who regularly use daytime oxygen therapy for more than one hour per day. 8. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program 9. Pregnant or nursing women 10. Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier).
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 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 on Week 24 | 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 Week 24 | 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 at week 24. | 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. |
| Mahler Transitional Dyspnea Index Focal Score at 24 Weeks | Baseline, Week 24 | Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). |
| Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis | Baseline, Week 24 | This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 on Week 2 | 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. |
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 on Week 6 | 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. |
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 Week 12 | 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. |
| Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 on Week 48 | 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 Week 2 | 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 at week 2. | 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 at Week 6 | 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 at week 6. | 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 at Week 12 | 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 at week 12. | 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 at Week 18 | 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 at week 18. | 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 at Week 32 | 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 at week 32. | 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 at Week 40 | 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 at week 40. | 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 at Week 48 | 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 at week 48. | 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 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 Hour (h) (AUC 0-3h) Response at 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 on Week 2 | Response was defined as change from baseline. Baseline FVC 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. FVC 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 Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 on Week 6 | Response was defined as change from baseline. Baseline FVC 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. FVC 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 Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 Week 12 | Response was defined as change from baseline. Baseline FVC 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. FVC 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 Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 on Week 24 | Response was defined as change from baseline. Baseline FVC 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. FVC 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 Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 on Week 48 | Response was defined as change from baseline. Baseline FVC 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. FVC 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 FVC Response at Week 2 | 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 at week 2. | 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 FVC performed 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 at Week 6 | 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 at week 6. | 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 FVC performed 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 at Week 12 | 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 at week 12. | 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 FVC performed 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 at Week 18 | 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 at week 18. | 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 FVC performed 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 at Week 24 | 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 at week 24. | 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 FVC performed 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 at Week 32 | 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 at week 32. | 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 FVC performed 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 at Week 48 | 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 at week 48. | 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 FVC performed 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 at Week 40 | 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 at week 40. | 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 FVC performed 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. |
| Peak FVC (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 FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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 FVC (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 FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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 FVC (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 FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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 FVC (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 FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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 FVC (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 FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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 Expiratory Flow Rate (PEFR) at Week 24 | Week 24 | Weekly mean pre-dose morning and evening PEFR. Results are from non-MMRM ANCOVA models by week, with Last observation carried forward (LOCF) up to each week. Fixed effects include treatment, tiotropium, strata and baseline. |
| Use of Rescue Medication at Week 24 | Week 24 | Mean number of puffs of rescue medication used per day (daytime/nighttime/total) |
| Patient's Global Rating (PGR) at 6 Weeks | Week 6 | Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). |
| Patient's Global Rating (PGR) at 12 Weeks | Week 12 | Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). |
| Patient's Global Rating (PGR) at 24 Weeks | Week 24 | Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). |
| Patient's Global Rating (PGR) at 48 Weeks | Week 48 | Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). |
| Mahler Transitional Dyspnea Index Focal Score at 6 Weeks | Baseline, Week 6 | Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). |
| Mahler Transitional Dyspnea Index Focal Score at 12 Weeks | Baseline, Week 12 | Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). |
| Mahler Transitional Dyspnea Index Focal Score at 18 Weeks | Baseline, Week 18 | Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). |
| Mahler Transitional Dyspnea Index Focal Score at 32 Weeks | Baseline, Week 32 | Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). |
| Mahler Transitional Dyspnea Index Focal Score at 40 Weeks | Baseline, Week 40 | Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). |
| Mahler Transitional Dyspnea Index Focal Score at 48 Weeks | Baseline, Week 48 | Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). |
| 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. |
| Time to First Chronic Obstructive Pulmonary Disease (CPOD) 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. |
| Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) 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. |
| 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. |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks | Baseline, Week 24 | Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). |
| Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) 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. |
| Absolute Plasma Concentrations | within 2 hours before first drug administration and 10 minutes post-dose at week 6, 12 and 18 | Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means. |
| Changes in Safety Parameters Related to Treatment | 48 weeks | Occurence of cardiac disorders and investigations related to treatment. |
| 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. |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks | Baseline, Week 12 | Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks | Baseline, Week 48 | Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis | Baseline, Week 24 | Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). This is a combined analysis of the data from NCT00793624 and NCT00796653 showing adjusted values using a MMRM model. |
Countries
Argentina, Brazil, Canada, Croatia, Czechia, Denmark, Finland, Germany, Hong Kong, India, Italy, Malaysia, Norway, Philippines, South Africa, South Korea, Spain, Sweden, Thailand, Ukraine
Participant flow
Pre-assignment details
Two subjects were randomized but not treated due to withdrawn consent and inability to perform spirometry prior to dosing.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Placebo delivered by the Respimat Inhaler. | 225 |
| Olo 5 mcg qd Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler. | 227 |
| Olo 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler. | 225 |
| Form 12 mcg Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler. | 227 |
| Total | 904 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 18 | 16 | 15 | 20 |
| Overall Study | Lack of Efficacy | 9 | 2 | 1 | 3 |
| Overall Study | Lost to Follow-up | 2 | 2 | 4 | 0 |
| Overall Study | Non compliance with protocol | 2 | 3 | 2 | 3 |
| Overall Study | Other reason not described above | 6 | 4 | 6 | 3 |
| Overall Study | Withdrawal by Subject | 20 | 9 | 11 | 14 |
Baseline characteristics
| Characteristic | Placebo | Olo 5 mcg qd | Olo 10 mcg qd | Form 12 mcg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 8.4 | 63.7 years STANDARD_DEVIATION 9.1 | 62.6 years STANDARD_DEVIATION 8.8 | 64.8 years STANDARD_DEVIATION 8.6 | 63.8 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 45 Participants | 50 Participants | 55 Participants | 48 Participants | 198 Participants |
| Sex: Female, Male Male | 180 Participants | 177 Participants | 170 Participants | 179 Participants | 706 Participants |
| Tiotropium (Tio) Use Stratum Non-tiotropium | 169 Number of participants | 168 Number of participants | 167 Number of participants | 169 Number of participants | 673 Number of participants |
| Tiotropium (Tio) Use Stratum Tiotropium | 56 Number of participants | 59 Number of participants | 58 Number of participants | 58 Number of participants | 231 Number of participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 83 / 225 | 100 / 227 | 96 / 225 | 83 / 227 |
| serious Total, serious adverse events | 31 / 225 | 33 / 227 | 26 / 225 | 33 / 227 |
Outcome results
Primary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 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 Week 24
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks | -0.009 Liter | Standard Error 0.016 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks | 0.142 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks | 0.156 Liter | Standard Error 0.015 |
| Form 12 mcg | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks | 0.168 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.11, 0.193]Mixed Models Analysis
p-value: <0.000195% CI: [0.124, 0.206]Mixed Models Analysis
p-value: <0.000195% CI: [0.136, 0.218]Mixed Models Analysis
Primary
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time frame: Baseline, Week 24
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mahler Transitional Dyspnea Index Focal Score at 24 Weeks | 2.046 score on a scale | Standard Error 0.255 |
| Olo 5 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 24 Weeks | 2.234 score on a scale | Standard Error 0.24 |
| Olo 10 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 24 Weeks | 2.068 score on a scale | Standard Error 0.245 |
| Form 12 mcg | Mahler Transitional Dyspnea Index Focal Score at 24 Weeks | 1.818 score on a scale | Standard Error 0.247 |
p-value: 0.584395% CI: [-0.485, 0.86]Mixed Models Analysis
p-value: 0.949495% CI: [-0.656, 0.699]Mixed Models Analysis
p-value: 0.509995% CI: [-0.908, 0.451]Mixed Models Analysis
Primary
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis
This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time frame: Baseline, Week 24
Population: Full analysis sets (FAS) of the trials NCT00793624 and NCT00796653. 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis | 1.471 score on a scale | Standard Error 0.155 |
| Olo 5 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis | 1.980 score on a scale | Standard Error 0.175 |
| Olo 10 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis | 1.996 score on a scale | Standard Error 0.17 |
| Form 12 mcg | Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis | 1.827 score on a scale | Standard Error 0.168 |
Comparison: Olo 5mcg minus placebop-value: 0.02795% CI: [0.058, 0.96]pattern mixture model
Comparison: Olo 10 mcg minus placebop-value: 0.020395% CI: [0.082, 0.967]pattern mixture model
Comparison: Form 12mcg minus placebop-value: 0.116695% CI: [-0.088, 0.799]pattern mixture model
Primary
Trough FEV1 Response at Week 24
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 at week 24.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Week 24 | -0.056 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Trough FEV1 Response at Week 24 | 0.021 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Trough FEV1 Response at Week 24 | 0.028 Liter | Standard Error 0.015 |
| Form 12 mcg | Trough FEV1 Response at Week 24 | -0.002 Liter | Standard Error 0.015 |
p-value: 0.000295% CI: [0.037, 0.118]Mixed Models Analysis
p-value: <0.000195% CI: [0.044, 0.125]Mixed Models Analysis
p-value: 0.008895% CI: [0.014, 0.095]Mixed Models Analysis
Secondary
Absolute Plasma Concentrations
Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means.
Time frame: within 2 hours before first drug administration and 10 minutes post-dose at week 6, 12 and 18
Population: Pharmacokinetic set includes all patients in the treated set who had at least one valid olodaterol plasma concentration measurement after initial administration of study drug. This set is restricted to patients in either the Olodaterol 5 μg or 10 μg dose group.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Olo 5 mcg qd | Absolute Plasma Concentrations | 4.179 pg/mL | Geometric Coefficient of Variation 60.3 |
| Olo 10 mcg qd | Absolute Plasma Concentrations | 7.246 pg/mL | Geometric Coefficient of Variation 72.242 |
Secondary
Changes in Safety Parameters Related to Treatment
Occurence of cardiac disorders and investigations related to treatment.
Time frame: 48 weeks
Population: Treated set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Changes in Safety Parameters Related to Treatment | Palpitations | 0.4 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Arrhythmia | 0.0 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Atrial fibrillation | 0.4 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Atrioventricular block | 0.4 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Atrioventricular block first degree | 0.0 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Bundle branch block right | 0.0 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Ventricular extrasystoles | 0.4 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Electrocardiogram QT prolonged | 0.0 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Electrocardiogram T wave inversion | 0.0 percentage of participants |
| Placebo | Changes in Safety Parameters Related to Treatment | Tachycardia | 0.4 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Ventricular extrasystoles | 0.0 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Bundle branch block right | 0.4 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Atrial fibrillation | 0.0 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Electrocardiogram T wave inversion | 0.0 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Palpitations | 0.0 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Electrocardiogram QT prolonged | 0.4 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Arrhythmia | 0.4 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Atrioventricular block first degree | 0.0 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Atrioventricular block | 0.0 percentage of participants |
| Olo 5 mcg qd | Changes in Safety Parameters Related to Treatment | Tachycardia | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Palpitations | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Electrocardiogram QT prolonged | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Atrioventricular block | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Atrioventricular block first degree | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Bundle branch block right | 0.0 percentage of participants |
| Olo 10 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 | Ventricular extrasystoles | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Tachycardia | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Electrocardiogram T wave inversion | 0.0 percentage of participants |
| Olo 10 mcg qd | Changes in Safety Parameters Related to Treatment | Arrhythmia | 0.0 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Ventricular extrasystoles | 0.0 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Atrioventricular block first degree | 0.4 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Arrhythmia | 0.0 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Tachycardia | 0.9 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Atrioventricular block | 0.0 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Electrocardiogram QT prolonged | 0.4 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Palpitations | 0.4 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Bundle branch block right | 0.0 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Electrocardiogram T wave inversion | 0.4 percentage of participants |
| Form 12 mcg | Changes in Safety Parameters Related to Treatment | Atrial fibrillation | 0.4 percentage of participants |
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 Week 12
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks | -0.003 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks | 0.176 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks | 0.167 Liter | Standard Error 0.015 |
| Form 12 mcg | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks | 0.182 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.137, 0.219]Mixed Models Analysis
p-value: <0.000195% CI: [0.129, 0.211]Mixed Models Analysis
p-value: <0.000195% CI: [0.144, 0.226]Mixed Models Analysis
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 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 Week 2
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks | 0.015 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks | 0.201 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks | 0.181 Liter | Standard Error 0.015 |
| Form 12 mcg | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks | 0.221 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.126, 0.206]Mixed Models Analysis
p-value: <0.000195% CI: [0.146, 0.226]Mixed Models Analysis
p-value: <0.000195% CI: [0.166, 0.246]Mixed Models Analysis
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 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 Week 48
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks | -0.023 Liter | Standard Error 0.016 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks | 0.122 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks | 0.123 Liter | Standard Error 0.015 |
| Form 12 mcg | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks | 0.149 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.103, 0.186]Mixed Models Analysis
p-value: <0.000195% CI: [0.105, 0.188]Mixed Models Analysis
p-value: <0.000195% CI: [0.13, 0.214]Mixed Models Analysis
Secondary
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 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 Week 6
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks | 0.001 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks | 0.178 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks | 0.161 Liter | Standard Error 0.015 |
| Form 12 mcg | Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks | 0.194 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.136, 0.217]Mixed Models Analysis
p-value: <0.000195% CI: [0.119, 0.2]Mixed Models Analysis
p-value: <0.000195% CI: [0.152, 0.233]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
Response was defined as change from baseline. Baseline FVC 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. FVC 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 Week 12
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks | 0.023 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks | 0.233 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks | 0.278 Liter | Standard Error 0.027 |
| Form 12 mcg | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks | 0.300 Liter | Standard Error 0.028 |
p-value: <0.000195% CI: [0.135, 0.285]Mixed Models Analysis
p-value: <0.000195% CI: [0.179, 0.329]Mixed Models Analysis
p-value: <0.000195% CI: [0.201, 0.352]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
Response was defined as change from baseline. Baseline FVC 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. FVC 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 Week 24
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks | 0.037 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks | 0.220 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks | 0.252 Liter | Standard Error 0.028 |
| Form 12 mcg | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks | 0.279 Liter | Standard Error 0.028 |
p-value: <0.000195% CI: [0.107, 0.258]Mixed Models Analysis
p-value: <0.000195% CI: [0.139, 0.291]Mixed Models Analysis
p-value: <0.000195% CI: [0.166, 0.318]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
Response was defined as change from baseline. Baseline FVC 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. FVC 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 Week 2
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks | 0.076 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks | 0.299 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks | 0.311 Liter | Standard Error 0.027 |
| Form 12 mcg | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks | 0.383 Liter | Standard Error 0.027 |
p-value: <0.000195% CI: [0.149, 0.297]Mixed Models Analysis
p-value: <0.000195% CI: [0.161, 0.309]Mixed Models Analysis
p-value: <0.000195% CI: [0.233, 0.381]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
Response was defined as change from baseline. Baseline FVC 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. FVC 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 Week 48
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks | 0.016 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks | 0.196 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks | 0.219 Liter | Standard Error 0.028 |
| Form 12 mcg | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks | 0.260 Liter | Standard Error 0.028 |
p-value: <0.000195% CI: [0.103, 0.256]Mixed Models Analysis
p-value: <0.000195% CI: [0.126, 0.28]Mixed Models Analysis
p-value: <0.000195% CI: [0.166, 0.32]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
Response was defined as change from baseline. Baseline FVC 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. FVC 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 Week 6
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks | 0.016 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks | 0.252 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks | 0.265 Liter | Standard Error 0.027 |
| Form 12 mcg | Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks | 0.326 Liter | Standard Error 0.027 |
p-value: <0.000195% CI: [0.161, 0.31]Mixed Models Analysis
p-value: <0.000195% CI: [0.175, 0.324]Mixed Models Analysis
p-value: <0.000195% CI: [0.235, 0.384]Mixed Models Analysis
Secondary
Mahler Transitional Dyspnea Index Focal Score at 12 Weeks
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time frame: Baseline, Week 12
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mahler Transitional Dyspnea Index Focal Score at 12 Weeks | 1.412 score on a scale | Standard Error 0.252 |
| Olo 5 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 12 Weeks | 1.792 score on a scale | Standard Error 0.239 |
| Olo 10 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 12 Weeks | 1.955 score on a scale | Standard Error 0.242 |
| Form 12 mcg | Mahler Transitional Dyspnea Index Focal Score at 12 Weeks | 1.805 score on a scale | Standard Error 0.245 |
p-value: 0.262595% CI: [-0.285, 1.047]Mixed Models Analysis
p-value: 0.110995% CI: [-0.125, 1.211]Mixed Models Analysis
p-value: 0.250795% CI: [-0.278, 1.066]Mixed Models Analysis
Secondary
Mahler Transitional Dyspnea Index Focal Score at 18 Weeks
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time frame: Baseline, Week 18
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mahler Transitional Dyspnea Index Focal Score at 18 Weeks | 1.665 score on a scale | Standard Error 0.254 |
| Olo 5 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 18 Weeks | 1.897 score on a scale | Standard Error 0.24 |
| Olo 10 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 18 Weeks | 2.099 score on a scale | Standard Error 0.244 |
| Form 12 mcg | Mahler Transitional Dyspnea Index Focal Score at 18 Weeks | 1.689 score on a scale | Standard Error 0.246 |
p-value: 0.489595% CI: [-0.439, 0.902]Mixed Models Analysis
p-value: 0.207395% CI: [-0.24, 1.107]Mixed Models Analysis
p-value: 0.946295% CI: [-0.653, 0.7]Mixed Models Analysis
Secondary
Mahler Transitional Dyspnea Index Focal Score at 32 Weeks
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time frame: Baseline, Week 32
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mahler Transitional Dyspnea Index Focal Score at 32 Weeks | 1.732 score on a scale | Standard Error 0.257 |
| Olo 5 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 32 Weeks | 1.898 score on a scale | Standard Error 0.241 |
| Olo 10 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 32 Weeks | 1.698 score on a scale | Standard Error 0.247 |
| Form 12 mcg | Mahler Transitional Dyspnea Index Focal Score at 32 Weeks | 1.966 score on a scale | Standard Error 0.249 |
p-value: 0.630995% CI: [-0.511, 0.842]Mixed Models Analysis
p-value: 0.922795% CI: [-0.717, 0.649]Mixed Models Analysis
p-value: 0.50395% CI: [-0.451, 0.919]Mixed Models Analysis
Secondary
Mahler Transitional Dyspnea Index Focal Score at 40 Weeks
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time frame: Baseline, Week 40
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mahler Transitional Dyspnea Index Focal Score at 40 Weeks | 1.952 score on a scale | Standard Error 0.259 |
| Olo 5 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 40 Weeks | 1.839 score on a scale | Standard Error 0.241 |
| Olo 10 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 40 Weeks | 1.887 score on a scale | Standard Error 0.249 |
| Form 12 mcg | Mahler Transitional Dyspnea Index Focal Score at 40 Weeks | 1.575 score on a scale | Standard Error 0.251 |
p-value: 0.745995% CI: [-0.793, 0.568]Mixed Models Analysis
p-value: 0.853495% CI: [-0.753, 0.623]Mixed Models Analysis
p-value: 0.509995% CI: [-1.068, 0.314]Mixed Models Analysis
Secondary
Mahler Transitional Dyspnea Index Focal Score at 48 Weeks
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time frame: Baseline, Week 48
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mahler Transitional Dyspnea Index Focal Score at 48 Weeks | 1.940 score on a scale | Standard Error 0.259 |
| Olo 5 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 48 Weeks | 2.035 score on a scale | Standard Error 0.242 |
| Olo 10 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 48 Weeks | 2.324 score on a scale | Standard Error 0.25 |
| Form 12 mcg | Mahler Transitional Dyspnea Index Focal Score at 48 Weeks | 2.047 score on a scale | Standard Error 0.251 |
p-value: 0.78595% CI: [-0.587, 0.777]Mixed Models Analysis
p-value: 0.275595% CI: [-0.306, 1.073]Mixed Models Analysis
p-value: 0.761895% CI: [-0.584, 0.798]Mixed Models Analysis
Secondary
Mahler Transitional Dyspnea Index Focal Score at 6 Weeks
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time frame: Baseline, Week 6
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mahler Transitional Dyspnea Index Focal Score at 6 Weeks | 0.995 score on a scale | Standard Error 0.248 |
| Olo 5 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 6 Weeks | 1.566 score on a scale | Standard Error 0.236 |
| Olo 10 mcg qd | Mahler Transitional Dyspnea Index Focal Score at 6 Weeks | 1.660 score on a scale | Standard Error 0.24 |
| Form 12 mcg | Mahler Transitional Dyspnea Index Focal Score at 6 Weeks | 1.753 score on a scale | Standard Error 0.243 |
p-value: 0.088295% CI: [-0.085, 1.227]Mixed Models Analysis
p-value: 0.048495% CI: [0.005, 1.324]Mixed Models Analysis
p-value: 0.025295% CI: [0.094, 1.421]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 | 0.5684 Number of COPD ex. per patient year | Standard Error 0.0718 |
| Olo 5 mcg qd | Number of COPD Exacerbations | 0.7117 Number of COPD ex. per patient year | Standard Error 0.0793 |
| Olo 10 mcg qd | Number of COPD Exacerbations | 0.6946 Number of COPD ex. per patient year | Standard Error 0.0801 |
| Form 12 mcg | Number of COPD Exacerbations | 0.5098 Number of COPD ex. per patient year | Standard Error 0.0649 |
p-value: 0.172995% CI: [0.906, 1.7304]Negative binomial regression
p-value: 0.229795% CI: [0.8808, 1.6954]Negative binomial regression
p-value: 0.535495% CI: [0.6353, 1.2659]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 | 0.0554 Number of COPD ex. per patient year | Standard Error 0.0249 |
| Olo 5 mcg qd | Number of COPD Exacerbations Requiring Hospitalization | 0.1043 Number of COPD ex. per patient year | Standard Error 0.0378 |
| Olo 10 mcg qd | Number of COPD Exacerbations Requiring Hospitalization | 0.1324 Number of COPD ex. per patient year | Standard Error 0.0493 |
| Form 12 mcg | Number of COPD Exacerbations Requiring Hospitalization | 0.0570 Number of COPD ex. per patient year | Standard Error 0.0227 |
p-value: 0.250895% CI: [0.6391, 5.543]Negative binomial regression
p-value: 0.113595% CI: [0.8122, 7.0194]Negative binomial regression
p-value: 0.961195% CI: [0.3268, 3.2395]Negative binomial regression
Secondary
Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) 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.
Population: Treated set- all patients who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations | 0.4765 Number of COPD ex. per patient year | Standard Error 0.0645 |
| Olo 5 mcg qd | Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations | 0.5537 Number of COPD ex. per patient year | Standard Error 0.0674 |
| Olo 10 mcg qd | Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations | 0.5114 Number of COPD ex. per patient year | Standard Error 0.0654 |
| Form 12 mcg | Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations | 0.3721 Number of COPD ex. per patient year | Standard Error 0.0537 |
p-value: 0.400295% CI: [0.8187, 1.6497]Negative binomial regression
p-value: 0.698395% CI: [0.7503, 1.5352]Negative binomial regression
p-value: 0.203395% CI: [0.5336, 1.1433]Negative binomial regression
Secondary
Patient's Global Rating (PGR) at 12 Weeks
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time frame: Week 12
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient's Global Rating (PGR) at 12 Weeks | 3.3 score on a scale | Standard Error 0.1 |
| Olo 5 mcg qd | Patient's Global Rating (PGR) at 12 Weeks | 3.0 score on a scale | Standard Error 0.1 |
| Olo 10 mcg qd | Patient's Global Rating (PGR) at 12 Weeks | 2.9 score on a scale | Standard Error 0.1 |
| Form 12 mcg | Patient's Global Rating (PGR) at 12 Weeks | 3.0 score on a scale | Standard Error 0.1 |
p-value: 0.002195% CI: [-0.5, -0.1]Mixed Models Analysis
p-value: <0.000195% CI: [-0.6, -0.2]Mixed Models Analysis
p-value: 0.012195% CI: [-0.5, -0.1]Mixed Models Analysis
Secondary
Patient's Global Rating (PGR) at 24 Weeks
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time frame: Week 24
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient's Global Rating (PGR) at 24 Weeks | 3.1 score on a scale | Standard Error 0.1 |
| Olo 5 mcg qd | Patient's Global Rating (PGR) at 24 Weeks | 2.9 score on a scale | Standard Error 0.1 |
| Olo 10 mcg qd | Patient's Global Rating (PGR) at 24 Weeks | 2.9 score on a scale | Standard Error 0.1 |
| Form 12 mcg | Patient's Global Rating (PGR) at 24 Weeks | 3.0 score on a scale | Standard Error 0.1 |
p-value: 0.03295% CI: [-0.4, 0]Mixed Models Analysis
p-value: 0.044795% CI: [-0.4, 0]Mixed Models Analysis
p-value: 0.133295% CI: [-0.4, 0]Mixed Models Analysis
Secondary
Patient's Global Rating (PGR) at 48 Weeks
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time frame: Week 48
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient's Global Rating (PGR) at 48 Weeks | 3.1 score on a scale | Standard Error 0.1 |
| Olo 5 mcg qd | Patient's Global Rating (PGR) at 48 Weeks | 3.0 score on a scale | Standard Error 0.1 |
| Olo 10 mcg qd | Patient's Global Rating (PGR) at 48 Weeks | 2.9 score on a scale | Standard Error 0.1 |
| Form 12 mcg | Patient's Global Rating (PGR) at 48 Weeks | 2.9 score on a scale | Standard Error 0.1 |
p-value: 0.410595% CI: [-0.3, 0.1]Mixed Models Analysis
p-value: 0.058495% CI: [-0.4, 0]Mixed Models Analysis
p-value: 0.100695% CI: [-0.4, 0]Mixed Models Analysis
Secondary
Patient's Global Rating (PGR) at 6 Weeks
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time frame: Week 6
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient's Global Rating (PGR) at 6 Weeks | 3.4 score on a scale | Standard Error 0.1 |
| Olo 5 mcg qd | Patient's Global Rating (PGR) at 6 Weeks | 3.0 score on a scale | Standard Error 0.1 |
| Olo 10 mcg qd | Patient's Global Rating (PGR) at 6 Weeks | 3.1 score on a scale | Standard Error 0.1 |
| Form 12 mcg | Patient's Global Rating (PGR) at 6 Weeks | 3.1 score on a scale | Standard Error 0.1 |
p-value: 0.000395% CI: [-0.6, -0.2]Mixed Models Analysis
p-value: 0.007395% CI: [-0.5, -0.1]Mixed Models Analysis
p-value: 0.001795% CI: [-0.5, -0.1]Mixed Models Analysis
Secondary
Peak Expiratory Flow Rate (PEFR) at Week 24
Weekly mean pre-dose morning and evening PEFR. Results are from non-MMRM ANCOVA models by week, with Last observation carried forward (LOCF) up to each week. Fixed effects include treatment, tiotropium, strata and baseline.
Time frame: Week 24
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Peak Expiratory Flow Rate (PEFR) at Week 24 | morning PEFR (N=214, 212, 216, 218) | 196.429 L/min | Standard Error 3.392 |
| Placebo | Peak Expiratory Flow Rate (PEFR) at Week 24 | evening PEFR (N=215, 211, 215, 221) | 202.256 L/min | Standard Error 3.363 |
| Olo 5 mcg qd | Peak Expiratory Flow Rate (PEFR) at Week 24 | evening PEFR (N=215, 211, 215, 221) | 219.977 L/min | Standard Error 3.408 |
| Olo 5 mcg qd | Peak Expiratory Flow Rate (PEFR) at Week 24 | morning PEFR (N=214, 212, 216, 218) | 211.496 L/min | Standard Error 3.42 |
| Olo 10 mcg qd | Peak Expiratory Flow Rate (PEFR) at Week 24 | morning PEFR (N=214, 212, 216, 218) | 211.428 L/min | Standard Error 3.379 |
| Olo 10 mcg qd | Peak Expiratory Flow Rate (PEFR) at Week 24 | evening PEFR (N=215, 211, 215, 221) | 220.727 L/min | Standard Error 3.36 |
| Form 12 mcg | Peak Expiratory Flow Rate (PEFR) at Week 24 | morning PEFR (N=214, 212, 216, 218) | 214.070 L/min | Standard Error 3.373 |
| Form 12 mcg | Peak Expiratory Flow Rate (PEFR) at Week 24 | evening PEFR (N=215, 211, 215, 221) | 220.129 L/min | Standard Error 3.332 |
Comparison: Comparison for Weekly mean morning PEFRp-value: 0.001295% CI: [5.962, 24.173]ANCOVA
Comparison: Comparison for Weekly mean morning PEFRp-value: 0.001295% CI: [5.949, 24.049]ANCOVA
Comparison: Comparison for Weekly mean morning PEFRp-value: 0.000195% CI: [8.61, 26.673]ANCOVA
Comparison: Comparison for Weekly mean evening PEFRp-value: 0.000195% CI: [8.68, 26.762]ANCOVA
Comparison: Comparison for Weekly mean evening PEFRp-value: <0.000195% CI: [9.484, 27.458]ANCOVA
Comparison: Comparison for Weekly mean evening PEFRp-value: <0.000195% CI: [8.947, 26.799]ANCOVA
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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 12 Weeks | 0.082 Liter | Standard Error 0.016 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 12 Weeks | 0.247 Liter | Standard Error 0.016 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 12 Weeks | 0.241 Liter | Standard Error 0.016 |
| Form 12 mcg | Peak FEV1 (0-3h) Response After 12 Weeks | 0.256 Liter | Standard Error 0.016 |
p-value: <0.000195% CI: [0.122, 0.208]Mixed Models Analysis
p-value: <0.000195% CI: [0.116, 0.203]Mixed Models Analysis
p-value: <0.000195% CI: [0.13, 0.218]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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 24 Weeks | 0.068 Liter | Standard Error 0.017 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 24 Weeks | 0.216 Liter | Standard Error 0.016 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 24 Weeks | 0.225 Liter | Standard Error 0.016 |
| Form 12 mcg | Peak FEV1 (0-3h) Response After 24 Weeks | 0.236 Liter | Standard Error 0.016 |
p-value: <0.000195% CI: [0.104, 0.191]Mixed Models Analysis
p-value: <0.000195% CI: [0.112, 0.2]Mixed Models Analysis
p-value: <0.000195% CI: [0.123, 0.211]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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 2 Weeks | 0.100 Liter | Standard Error 0.016 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.277 Liter | Standard Error 0.016 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.250 Liter | Standard Error 0.016 |
| Form 12 mcg | Peak FEV1 (0-3h) Response After 2 Weeks | 0.290 Liter | Standard Error 0.016 |
p-value: <0.000195% CI: [0.135, 0.22]Mixed Models Analysis
p-value: <0.000195% CI: [0.108, 0.193]Mixed Models Analysis
p-value: <0.000195% CI: [0.148, 0.233]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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 48 Weeks | 0.053 Liter | Standard Error 0.017 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 48 Weeks | 0.192 Liter | Standard Error 0.016 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 48 Weeks | 0.193 Liter | Standard Error 0.016 |
| Form 12 mcg | Peak FEV1 (0-3h) Response After 48 Weeks | 0.215 Liter | Standard Error 0.016 |
p-value: <0.000195% CI: [0.095, 0.183]Mixed Models Analysis
p-value: <0.000195% CI: [0.095, 0.184]Mixed Models Analysis
p-value: <0.000195% CI: [0.117, 0.206]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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 6 Weeks | 0.081 Liter | Standard Error 0.016 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 6 Weeks | 0.248 Liter | Standard Error 0.016 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 6 Weeks | 0.234 Liter | Standard Error 0.016 |
| Form 12 mcg | Peak FEV1 (0-3h) Response After 6 Weeks | 0.264 Liter | Standard Error 0.016 |
p-value: <0.000195% CI: [0.124, 0.209]Mixed Models Analysis
p-value: <0.000195% CI: [0.109, 0.195]Mixed Models Analysis
p-value: <0.000195% CI: [0.139, 0.226]Mixed Models Analysis
Secondary
Peak FVC (0-3h) Response After 12 Weeks
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FVC (0-3h) Response After 12 Weeks | 0.194 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 12 Weeks | 0.382 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 12 Weeks | 0.432 Liter | Standard Error 0.029 |
| Form 12 mcg | Peak FVC (0-3h) Response After 12 Weeks | 0.450 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.108, 0.267]Mixed Models Analysis
p-value: <0.000195% CI: [0.159, 0.318]Mixed Models Analysis
p-value: <0.000195% CI: [0.177, 0.336]Mixed Models Analysis
Secondary
Peak FVC (0-3h) Response After 24 Weeks
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FVC (0-3h) Response After 24 Weeks | 0.207 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 24 Weeks | 0.379 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 24 Weeks | 0.414 Liter | Standard Error 0.029 |
| Form 12 mcg | Peak FVC (0-3h) Response After 24 Weeks | 0.424 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.092, 0.253]Mixed Models Analysis
p-value: <0.000195% CI: [0.127, 0.288]Mixed Models Analysis
p-value: <0.000195% CI: [0.137, 0.298]Mixed Models Analysis
Secondary
Peak FVC (0-3h) Response After 2 Weeks
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FVC (0-3h) Response After 2 Weeks | 0.268 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 2 Weeks | 0.454 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 2 Weeks | 0.474 Liter | Standard Error 0.028 |
| Form 12 mcg | Peak FVC (0-3h) Response After 2 Weeks | 0.551 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.108, 0.264]Mixed Models Analysis
p-value: <0.000195% CI: [0.128, 0.284]Mixed Models Analysis
p-value: <0.000195% CI: [0.205, 0.361]Mixed Models Analysis
Secondary
Peak FVC (0-3h) Response After 48 Weeks
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FVC (0-3h) Response After 48 Weeks | 0.193 Liter | Standard Error 0.031 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 48 Weeks | 0.344 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 48 Weeks | 0.371 Liter | Standard Error 0.03 |
| Form 12 mcg | Peak FVC (0-3h) Response After 48 Weeks | 0.416 Liter | Standard Error 0.03 |
p-value: 0.000395% CI: [0.07, 0.231]Mixed Models Analysis
p-value: <0.000195% CI: [0.096, 0.259]Mixed Models Analysis
p-value: <0.000195% CI: [0.141, 0.304]Mixed Models Analysis
Secondary
Peak FVC (0-3h) Response After 6 Weeks
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (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: 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FVC (0-3h) Response After 6 Weeks | 0.202 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 6 Weeks | 0.411 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 6 Weeks | 0.433 Liter | Standard Error 0.029 |
| Form 12 mcg | Peak FVC (0-3h) Response After 6 Weeks | 0.467 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.131, 0.288]Mixed Models Analysis
p-value: <0.000195% CI: [0.153, 0.31]Mixed Models Analysis
p-value: <0.000195% CI: [0.187, 0.344]Mixed Models Analysis
Secondary
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time frame: Baseline, Week 12
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks | 42.105 score on a scale | Standard Error 1.027 |
| Olo 5 mcg qd | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks | 39.320 score on a scale | Standard Error 0.986 |
| Olo 10 mcg qd | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks | 36.961 score on a scale | Standard Error 0.989 |
| Form 12 mcg | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks | 40.351 score on a scale | Standard Error 0.992 |
p-value: 0.04595% CI: [-5.507, -0.063]Mixed Models Analysis
p-value: 0.000295% CI: [-7.864, -2.425]Mixed Models Analysis
p-value: 0.206195% CI: [-4.474, 0.966]Mixed Models Analysis
Secondary
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time frame: Baseline, Week 24
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks | 41.068 score on a scale | Standard Error 1.038 |
| Olo 5 mcg qd | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks | 38.627 score on a scale | Standard Error 0.995 |
| Olo 10 mcg qd | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks | 37.674 score on a scale | Standard Error 0.998 |
| Form 12 mcg | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks | 40.116 score on a scale | Standard Error 0.994 |
p-value: 0.081695% CI: [-5.19, 0.307]Mixed Models Analysis
p-value: 0.015595% CI: [-6.141, -0.648]Mixed Models Analysis
p-value: 0.495495% CI: [-3.691, 1.787]Mixed Models Analysis
Secondary
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). This is a combined analysis of the data from NCT00793624 and NCT00796653 showing adjusted values using a MMRM model.
Time frame: Baseline, Week 24
Population: Full analysis sets (FAS) of the trials NCT00793624 and NCT00796653. 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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis | 41.639 score on a scale | Standard Error 0.718 |
| Olo 5 mcg qd | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis | 38.794 score on a scale | Standard Error 0.693 |
| Olo 10 mcg qd | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis | 38.205 score on a scale | Standard Error 0.695 |
| Form 12 mcg | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis | 40.391 score on a scale | Standard Error 0.699 |
Comparison: Olo 5 mcg qd minus Placebop-value: 0.003495% CI: [-4.751, -0.94]Mixed Models Analysis
Comparison: Olo 10 mcg qd minus Placebop-value: 0.000495% CI: [-5.343, -1.525]Mixed Models Analysis
Comparison: Form 10 mcg qd minus Placebop-value: 0.200995% CI: [-3.161, 0.665]Mixed Models Analysis
Secondary
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time frame: Baseline, Week 48
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 24 weeks for any of the co-primary efficacy variables.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks | 40.415 score on a scale | Standard Error 1.057 |
| Olo 5 mcg qd | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks | 38.545 score on a scale | Standard Error 1 |
| Olo 10 mcg qd | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks | 36.850 score on a scale | Standard Error 1.015 |
| Form 12 mcg | Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks | 40.431 score on a scale | Standard Error 1.015 |
p-value: 0.187895% CI: [-4.655, 0.914]Mixed Models Analysis
p-value: 0.012695% CI: [-6.364, -0.767]Mixed Models Analysis
p-value: 0.991395% CI: [-2.782, 2.814]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.
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 | 143 Days |
| Olo 5 mcg qd | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 268 Days |
| Olo 10 mcg qd | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 136 Days |
| Form 12 mcg | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 189 Days |
| Olo 10 mcg qd (Tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 134 Days |
| Olo 10 mcg qd(Non-tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 209 Days |
| Form 12 mcg (Tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 223 Days |
| Form 12 mcg (Non-tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 310 Days |
p-value: 0.342495% CI: [0.843, 1.603]Log Rank
p-value: 0.302395% CI: [0.859, 1.636]Log Rank
p-value: 0.358995% CI: [0.605, 1.205]Log Rank
Secondary
Time to First Chronic Obstructive Pulmonary Disease (CPOD) 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.
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 (CPOD) Exacerbation Leading to Hospitalization | NA Days |
| Olo 5 mcg qd | Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization | NA Days |
| Olo 10 mcg qd | Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization | NA Days |
| Form 12 mcg | Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization | NA Days |
| Olo 10 mcg qd (Tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization | NA Days |
| Olo 10 mcg qd(Non-tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization | NA Days |
| Form 12 mcg (Tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization | NA Days |
| Form 12 mcg (Non-tiotropium) | Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization | NA Days |
p-value: 0.19195% CI: [0.734, 4.503]Log Rank
p-value: 0.227495% CI: [0.695, 4.369]Log Rank
p-value: 0.553895% CI: [0.512, 3.538]Log Rank
Secondary
Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) 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.
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 (CPOD) Exacerbation | 150 Days |
| Olo 5 mcg qd | Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation | 296 Days |
| Olo 10 mcg qd | Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation | 239 Days |
| Form 12 mcg | Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation | 244 Days |
| Olo 10 mcg qd (Tiotropium) | Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation | 175 Days |
| Olo 10 mcg qd(Non-tiotropium) | Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation | 302 Days |
| Form 12 mcg (Tiotropium) | Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation | 280 Days |
| Form 12 mcg (Non-tiotropium) | Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation | 270 Days |
p-value: 0.557795% CI: [0.778, 1.557]Log Rank
p-value: 0.942395% CI: [0.714, 1.448]Log Rank
p-value: 0.109795% CI: [0.502, 1.076]Log Rank
Secondary
Trough FEV1 Response at Week 12
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 at week 12.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Week 12 | -0.027 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Trough FEV1 Response at Week 12 | 0.056 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response at Week 12 | 0.048 Liter | Standard Error 0.014 |
| Form 12 mcg | Trough FEV1 Response at Week 12 | 0.033 Liter | Standard Error 0.015 |
p-value: <0.000195% CI: [0.043, 0.123]Mixed Models Analysis
p-value: 0.000295% CI: [0.035, 0.114]Mixed Models Analysis
p-value: 0.003795% CI: [0.019, 0.1]Mixed Models Analysis
Secondary
Trough FEV1 Response at Week 18
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 at week 18.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Week 18 | -0.019 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Trough FEV1 Response at Week 18 | 0.046 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response at Week 18 | 0.026 Liter | Standard Error 0.015 |
| Form 12 mcg | Trough FEV1 Response at Week 18 | 0.023 Liter | Standard Error 0.015 |
p-value: 0.001695% CI: [0.025, 0.105]Mixed Models Analysis
p-value: 0.027695% CI: [0.005, 0.085]Mixed Models Analysis
p-value: 0.042695% CI: [0.001, 0.082]Mixed Models Analysis
Secondary
Trough FEV1 Response at Week 2
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 at week 2.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Week 2 | -0.019 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Trough FEV1 Response at Week 2 | 0.068 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response at Week 2 | 0.060 Liter | Standard Error 0.014 |
| Form 12 mcg | Trough FEV1 Response at Week 2 | 0.061 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.048, 0.126]Mixed Models Analysis
p-value: <0.000195% CI: [0.04, 0.118]Mixed Models Analysis
p-value: <0.000195% CI: [0.04, 0.119]Mixed Models Analysis
Secondary
Trough FEV1 Response at Week 32
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 at week 32.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Week 32 | -0.023 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Trough FEV1 Response at Week 32 | 0.023 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Trough FEV1 Response at Week 32 | 0.026 Liter | Standard Error 0.015 |
| Form 12 mcg | Trough FEV1 Response at Week 32 | 0.021 Liter | Standard Error 0.015 |
p-value: 0.023795% CI: [0.006, 0.087]Mixed Models Analysis
p-value: 0.017595% CI: [0.009, 0.09]Mixed Models Analysis
p-value: 0.033995% CI: [0.003, 0.085]Mixed Models Analysis
Secondary
Trough FEV1 Response at Week 40
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 at week 40.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Week 40 | -0.020 Liter | Standard Error 0.016 |
| Olo 5 mcg qd | Trough FEV1 Response at Week 40 | 0.020 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Trough FEV1 Response at Week 40 | 0.017 Liter | Standard Error 0.015 |
| Form 12 mcg | Trough FEV1 Response at Week 40 | 0.004 Liter | Standard Error 0.015 |
p-value: 0.053795% CI: [-0.001, 0.081]Mixed Models Analysis
p-value: 0.080895% CI: [-0.004, 0.078]Mixed Models Analysis
p-value: 0.257995% CI: [-0.017, 0.065]Mixed Models Analysis
Secondary
Trough FEV1 Response at Week 48
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 at week 48.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Week 48 | -0.065 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Trough FEV1 Response at Week 48 | 0.003 Liter | Standard Error 0.015 |
| Olo 10 mcg qd | Trough FEV1 Response at Week 48 | -0.009 Liter | Standard Error 0.015 |
| Form 12 mcg | Trough FEV1 Response at Week 48 | -0.006 Liter | Standard Error 0.015 |
p-value: 0.001195% CI: [0.027, 0.109]Mixed Models Analysis
p-value: 0.006995% CI: [0.018, 0.101]Mixed Models Analysis
p-value: <0.000195% CI: [0.04, 0.119]Mixed Models Analysis
Secondary
Trough FEV1 Response at Week 6
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 at week 6.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response at Week 6 | -0.037 Liter | Standard Error 0.015 |
| Olo 5 mcg qd | Trough FEV1 Response at Week 6 | 0.049 Liter | Standard Error 0.014 |
| Olo 10 mcg qd | Trough FEV1 Response at Week 6 | 0.041 Liter | Standard Error 0.014 |
| Form 12 mcg | Trough FEV1 Response at Week 6 | 0.042 Liter | Standard Error 0.014 |
p-value: <0.000195% CI: [0.047, 0.125]Mixed Models Analysis
p-value: 0.000195% CI: [0.038, 0.117]Mixed Models Analysis
p-value: <0.000195% CI: [0.039, 0.119]Mixed Models Analysis
Secondary
Trough FVC Response at Week 12
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 FVC performed 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 at week 12.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response at Week 12 | -0.018 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | Trough FVC Response at Week 12 | 0.079 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response at Week 12 | 0.087 Liter | Standard Error 0.028 |
| Form 12 mcg | Trough FVC Response at Week 12 | 0.068 Liter | Standard Error 0.028 |
p-value: 0.013695% CI: [0.02, 0.173]Mixed Models Analysis
p-value: 0.007695% CI: [0.028, 0.182]Mixed Models Analysis
p-value: 0.029495% CI: [0.009, 0.163]Mixed Models Analysis
Secondary
Trough FVC Response at Week 18
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 FVC performed 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 at week 18.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response at Week 18 | 0.060 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | Trough FVC Response at Week 18 | 0.066 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response at Week 18 | 0.078 Liter | Standard Error 0.028 |
| Form 12 mcg | Trough FVC Response at Week 18 | 0.063 Liter | Standard Error 0.028 |
p-value: 0.867495% CI: [-0.071, 0.084]Mixed Models Analysis
p-value: 0.648795% CI: [-0.06, 0.096]Mixed Models Analysis
p-value: 0.926795% CI: [-0.074, 0.081]Mixed Models Analysis
Secondary
Trough FVC Response at Week 2
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 FVC performed 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 at week 2.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response at Week 2 | 0.042 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Trough FVC Response at Week 2 | 0.110 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Trough FVC Response at Week 2 | 0.119 Liter | Standard Error 0.028 |
| Form 12 mcg | Trough FVC Response at Week 2 | 0.126 Liter | Standard Error 0.028 |
p-value: 0.078195% CI: [-0.008, 0.143]Mixed Models Analysis
p-value: 0.045595% CI: [0.002, 0.153]Mixed Models Analysis
p-value: 0.02995% CI: [0.009, 0.16]Mixed Models Analysis
Secondary
Trough FVC Response at Week 24
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 FVC performed 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 at week 24.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response at Week 24 | -0.018 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | Trough FVC Response at Week 24 | 0.038 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response at Week 24 | 0.064 Liter | Standard Error 0.028 |
| Form 12 mcg | Trough FVC Response at Week 24 | 0.001 Liter | Standard Error 0.029 |
p-value: 0.160395% CI: [-0.022, 0.134]Mixed Models Analysis
p-value: 0.039995% CI: [0.004, 0.16]Mixed Models Analysis
p-value: 0.632895% CI: [-0.059, 0.098]Mixed Models Analysis
Secondary
Trough FVC Response at Week 32
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 FVC performed 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 at week 32.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response at Week 32 | 0.019 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | Trough FVC Response at Week 32 | 0.080 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response at Week 32 | 0.084 Liter | Standard Error 0.028 |
| Form 12 mcg | Trough FVC Response at Week 32 | 0.077 Liter | Standard Error 0.029 |
p-value: 0.12795% CI: [-0.017, 0.139]Mixed Models Analysis
p-value: 0.107695% CI: [-0.014, 0.143]Mixed Models Analysis
p-value: 0.149295% CI: [-0.021, 0.137]Mixed Models Analysis
Secondary
Trough FVC Response at Week 40
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 FVC performed 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 at week 40.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response at Week 40 | 0.028 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | Trough FVC Response at Week 40 | 0.087 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response at Week 40 | 0.086 Liter | Standard Error 0.028 |
| Form 12 mcg | Trough FVC Response at Week 40 | 0.052 Liter | Standard Error 0.029 |
p-value: 0.139495% CI: [-0.019, 0.138]Mixed Models Analysis
p-value: 0.153295% CI: [-0.022, 0.137]Mixed Models Analysis
p-value: 0.551195% CI: [-0.055, 0.104]Mixed Models Analysis
Secondary
Trough FVC Response at Week 48
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 FVC performed 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 at week 48.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response at Week 48 | -0.061 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | Trough FVC Response at Week 48 | 0.022 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Trough FVC Response at Week 48 | -0.002 Liter | Standard Error 0.029 |
| Form 12 mcg | Trough FVC Response at Week 48 | 0.006 Liter | Standard Error 0.029 |
p-value: 0.038595% CI: [0.004, 0.162]Mixed Models Analysis
p-value: 0.14295% CI: [-0.02, 0.138]Mixed Models Analysis
p-value: 0.096595% CI: [-0.012, 0.147]Mixed Models Analysis
Secondary
Trough FVC Response at Week 6
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 FVC performed 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 at week 6.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response at Week 6 | -0.046 Liter | Standard Error 0.029 |
| Olo 5 mcg qd | Trough FVC Response at Week 6 | 0.065 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Trough FVC Response at Week 6 | 0.085 Liter | Standard Error 0.028 |
| Form 12 mcg | Trough FVC Response at Week 6 | 0.090 Liter | Standard Error 0.028 |
p-value: 0.004395% CI: [0.035, 0.186]Mixed Models Analysis
p-value: 0.000795% CI: [0.055, 0.207]Mixed Models Analysis
p-value: 0.000595% CI: [0.06, 0.212]Mixed Models Analysis
Secondary
Use of Rescue Medication at Week 24
Mean number of puffs of rescue medication used per day (daytime/nighttime/total)
Time frame: Week 24
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Use of Rescue Medication at Week 24 | Daytime | 1.364 Number of puffs | Standard Error 0.097 |
| Placebo | Use of Rescue Medication at Week 24 | Total | 3.390 Number of puffs | Standard Error 0.196 |
| Placebo | Use of Rescue Medication at Week 24 | Nighttime | 2.051 Number of puffs | Standard Error 0.125 |
| Olo 5 mcg qd | Use of Rescue Medication at Week 24 | Daytime | 0.961 Number of puffs | Standard Error 0.099 |
| Olo 5 mcg qd | Use of Rescue Medication at Week 24 | Total | 2.399 Number of puffs | Standard Error 0.198 |
| Olo 5 mcg qd | Use of Rescue Medication at Week 24 | Nighttime | 1.449 Number of puffs | Standard Error 0.126 |
| Olo 10 mcg qd | Use of Rescue Medication at Week 24 | Nighttime | 1.471 Number of puffs | Standard Error 0.125 |
| Olo 10 mcg qd | Use of Rescue Medication at Week 24 | Daytime | 1.037 Number of puffs | Standard Error 0.097 |
| Olo 10 mcg qd | Use of Rescue Medication at Week 24 | Total | 2.488 Number of puffs | Standard Error 0.196 |
| Form 12 mcg | Use of Rescue Medication at Week 24 | Daytime | 1.217 Number of puffs | Standard Error 0.097 |
| Form 12 mcg | Use of Rescue Medication at Week 24 | Total | 2.917 Number of puffs | Standard Error 0.195 |
| Form 12 mcg | Use of Rescue Medication at Week 24 | Nighttime | 1.701 Number of puffs | Standard Error 0.124 |
Comparison: Comparison for weekly mean daytime rescue usep-value: 0.002695% CI: [-0.665, -0.141]ANCOVA
Comparison: Comparison for weekly mean daytime rescue usep-value: 0.014195% CI: [-0.587, -0.066]ANCOVA
Comparison: Comparison for weekly mean daytime rescue usep-value: 0.267795% CI: [-0.406, 0.113]ANCOVA
Comparison: Comparison for weekly mean nighttime rescue usep-value: 0.000595% CI: [-0.939, -0.266]ANCOVA
Comparison: Comparison for weekly mean nighttime rescue usep-value: 0.000795% CI: [-0.914, -0.247]ANCOVA
Comparison: Comparison for weekly mean nighttime rescue usep-value: 0.039195% CI: [-0.683, -0.018]ANCOVA
Comparison: Comparison for weekly mean daily (24h) rescue usep-value: 0.000295% CI: [-1.518, -0.464]ANCOVA
Comparison: Comparison for weekly mean daily (24h) rescue usep-value: 0.000895% CI: [-1.426, -0.378]ANCOVA
Comparison: Comparison for weekly mean daily (24h) rescue usep-value: 0.075895% CI: [-0.994, 0.049]ANCOVA