Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The study is intended to characterize the lung function profile of BI1744 in COPD patients where patients will perform pulmonary function tests at regular intervals for 24 hours at the end of a 6 week treatment period. Each patient will receive all four treatments.
Interventions
DRUGBI 1744 (Olodaterol) Low Dose
BI1744 Respimat low dose once daily and placebo Foradil
DRUGBI 1744 (Olodaterol) Medium Dose
BI1744 Respimat medium dose once daily and placebo Foradil
DRUGPlacebo
Placebo Respimat once daily and placebo Foradil
DRUGForadil
12 mcg twice daily and placebo Respimat
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients willing to participate with confirmed diagnosis of COPD * 40 years of age or older * having a 10 pack year smoking history * able to perform serial pulmonary function tests * able to use both a DPI and Respimat device
Exclusion criteria
Significant other disease * clinically relevant abnormal hematology, chemistry, or urinalysis * history of asthma * diagnosis of thyrotoxicosis * paroxysmal tachycardia related to beta agonists * history of MI within 1 year, cardiac arrhythmia, hospitalization for heart failure within 1 year * active tuberculosis, cystic fibrosis, clinically evident bronchiectasis * significant alcohol or drug use * pulmonary resection * taking oral beta adrenergics * taking unstable oral steroids * daytime oxygen * enrolled in rehabilitation program * enrolled in another study or taking investigational products * pregnant or nursing women, women of child bearing potential not willing to use two methods of birth control * those who are not willing to comply with pulmonary medication washouts
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment | 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. |
| FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment | 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak FEV1 (0-3h) Response | Baseline and 6 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak values were obtained within 0 - 3 hours after the last am dose after six weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. |
| Trough FEV1 Response | Baseline and 6 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. |
| Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment | 1 h and 10 min prior to am dose on the first day of the treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment. | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres. |
| Peak FVC (0-3h) Response | Baseline and 6 weeks | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC was obtained within 0 - 3 hours after the last am dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. |
| Trough FVC Response | Baseline and 6 weeks | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. |
| Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | 6 weeks | Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations). |
| FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment. | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to am dose after six weeks of treatment | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-3h was calculated from 0-3hours post-dose using the trapezoidal rule, divided by the observation time (3 h) to report in litres. |
Countries
United States
Participant flow
Pre-assignment details
This was a randomised, double-blind, double dummy, placebo- and active-controlled, 4 way crossover trial. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments.
Participants by arm
| Arm | Count |
|---|---|
| Study Total Total number of patients treated in the study. This was a randomised, double-blind, double dummy, placebo- and active-controlled, 4 way crossover trial. 99 patients were assigned randomly to one of 4 treatment sequences in which they received each of 4 treatments, two doses (5 microgram (mcg) or 10 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo delivered by Respimat Inhaler or Aerolizer Inhaler. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments. | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Study Total |
|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 54 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 | 9 / 94 | 9 / 93 | 12 / 95 | 7 / 93 |
| serious Total, serious adverse events | 3 / 94 | 4 / 93 | 3 / 95 | 5 / 93 |
Outcome results
Primary
FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
Population: Full analysis set (FAS). FAS is defined as all patients with the baseline (pre-dose) date and any evaluable post-dosing data for the first co-primary endpoint FEV1AUC 0-12h.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment | -0.022 Liter | Standard Error 0.024 |
| Olo 5 mcg qd | FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment | 0.150 Liter | Standard Error 0.024 |
| Olo 10 mcg qd | FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment | 0.152 Liter | Standard Error 0.024 |
| Form 12 mcg Bid | FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment | 0.136 Liter | Standard Error 0.024 |
p-value: <0.000195% CI: [0.139, 0.205]Mixed Models Analysis
p-value: <0.000195% CI: [0.14, 0.208]Mixed Models Analysis
p-value: <0.000195% CI: [0.124, 0.191]Mixed Models Analysis
Primary
FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time frame: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
Population: Full analysis set (FAS).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment | -0.048 Liter | Standard Error 0.025 |
| Olo 5 mcg qd | FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment | 0.069 Liter | Standard Error 0.025 |
| Olo 10 mcg qd | FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment | 0.072 Liter | Standard Error 0.025 |
| Form 12 mcg Bid | FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment | 0.107 Liter | Standard Error 0.025 |
p-value: <0.000195% CI: [0.082, 0.154]Mixed Models Analysis
p-value: <0.000195% CI: [0.084, 0.157]Mixed Models Analysis
p-value: <0.000195% CI: [0.119, 0.191]Mixed Models Analysis
Secondary
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations).
Time frame: 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | ECG QT prolonged | 0 participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Tachycardia | 0 participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Bundle branch block right | 0 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | ECG QT prolonged | 0 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Tachycardia | 0 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Bundle branch block right | 0 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Bundle branch block right | 1 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | ECG QT prolonged | 1 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Tachycardia | 0 participants |
| Form 12 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | ECG QT prolonged | 0 participants |
| Form 12 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Tachycardia | 1 participants |
| Form 12 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Bundle branch block right | 0 participants |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.
Time frame: 1 h and 10 min prior to am dose on the first day of the treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment | -0.035 Liter | Standard Error 0.024 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment | 0.110 Liter | Standard Error 0.024 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment | 0.112 Liter | Standard Error 0.024 |
| Form 12 mcg Bid | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment | 0.121 Liter | Standard Error 0.024 |
p-value: <0.000195% CI: [0.114, 0.176]Mixed Models Analysis
p-value: <0.000195% CI: [0.116, 0.179]Mixed Models Analysis
p-value: <0.000195% CI: [0.125, 0.187]Mixed Models Analysis
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-3h was calculated from 0-3hours post-dose using the trapezoidal rule, divided by the observation time (3 h) to report in litres.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to am dose after six weeks of treatment
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment | 0.004 Liter | Standard Error 0.024 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment | 0.190 Liter | Standard Error 0.025 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment | 0.202 Liter | Standard Error 0.025 |
| Form 12 mcg Bid | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment | 0.217 Liter | Standard Error 0.025 |
p-value: <0.000195% CI: [0.149, 0.223]Mixed Models Analysis
p-value: <0.000195% CI: [0.162, 0.235]Mixed Models Analysis
p-value: <0.000195% CI: [0.176, 0.25]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | -0.032 Liter | Standard Error 0.04 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.219 Liter | Standard Error 0.04 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.214 Liter | Standard Error 0.04 |
| Form 12 mcg Bid | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.203 Liter | Standard Error 0.04 |
p-value: <0.000195% CI: [0.195, 0.306]Mixed Models Analysis
p-value: <0.000195% CI: [0.19, 0.302]Mixed Models Analysis
p-value: <0.000195% CI: [0.179, 0.291]Mixed Models Analysis
Secondary
FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | -0.055 Liter | Standard Error 0.039 |
| Olo 5 mcg qd | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.151 Liter | Standard Error 0.039 |
| Olo 10 mcg qd | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.147 Liter | Standard Error 0.039 |
| Form 12 mcg Bid | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.174 Liter | Standard Error 0.039 |
p-value: <0.000195% CI: [0.155, 0.258]Mixed Models Analysis
p-value: <0.000195% CI: [0.15, 0.255]Mixed Models Analysis
p-value: <0.000195% CI: [0.176, 0.281]Mixed Models Analysis
Secondary
FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | -0.078 Liter | Standard Error 0.041 |
| Olo 5 mcg qd | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.083 Liter | Standard Error 0.041 |
| Olo 10 mcg qd | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.079 Liter | Standard Error 0.041 |
| Form 12 mcg Bid | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.144 Liter | Standard Error 0.041 |
p-value: <0.000195% CI: [0.101, 0.222]Mixed Models Analysis
p-value: <0.000195% CI: [0.096, 0.218]Mixed Models Analysis
p-value: <0.000195% CI: [0.162, 0.284]Mixed Models Analysis
Secondary
Peak FEV1 (0-3h) Response
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak values were obtained within 0 - 3 hours after the last am dose after six weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.
Time frame: Baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response | 0.076 Liter | Standard Error 0.026 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response | 0.268 Liter | Standard Error 0.026 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response | 0.273 Liter | Standard Error 0.026 |
| Form 12 mcg Bid | Peak FEV1 (0-3h) Response | 0.293 Liter | Standard Error 0.026 |
p-value: <0.000195% CI: [0.154, 0.23]Mixed Models Analysis
p-value: <0.000195% CI: [0.158, 0.235]Mixed Models Analysis
p-value: <0.000195% CI: [0.178, 0.255]Mixed Models Analysis
Secondary
Peak FVC (0-3h) Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC was obtained within 0 - 3 hours after the last am dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.
Time frame: Baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FVC (0-3h) Response | 0.138 Liter | Standard Error 0.043 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response | 0.436 Liter | Standard Error 0.043 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response | 0.440 Liter | Standard Error 0.043 |
| Form 12 mcg Bid | Peak FVC (0-3h) Response | 0.475 Liter | Standard Error 0.043 |
p-value: <0.000195% CI: [0.233, 0.365]Mixed Models Analysis
p-value: <0.000195% CI: [0.236, 0.369]Mixed Models Analysis
p-value: <0.000195% CI: [0.271, 0.405]Mixed Models Analysis
Secondary
Trough FEV1 Response
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.
Time frame: Baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response | 0.012 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | Trough FEV1 Response | 0.109 Liter | Standard Error 0.03 |
| Olo 10 mcg qd | Trough FEV1 Response | 0.115 Liter | Standard Error 0.03 |
| Form 12 mcg Bid | Trough FEV1 Response | 0.093 Liter | Standard Error 0.03 |
p-value: 0.000395% CI: [0.045, 0.148]Mixed Models Analysis
p-value: 0.000195% CI: [0.051, 0.155]Mixed Models Analysis
p-value: 0.002695% CI: [0.028, 0.132]Mixed Models Analysis
Secondary
Trough FVC Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.
Time frame: Baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response | -0.007 Liter | Standard Error 0.053 |
| Olo 5 mcg qd | Trough FVC Response | 0.125 Liter | Standard Error 0.053 |
| Olo 10 mcg qd | Trough FVC Response | 0.133 Liter | Standard Error 0.054 |
| Form 12 mcg Bid | Trough FVC Response | 0.141 Liter | Standard Error 0.054 |
p-value: 0.016395% CI: [0.024, 0.239]Mixed Models Analysis
p-value: 0.011895% CI: [0.031, 0.247]Mixed Models Analysis
p-value: 0.007695% CI: [0.04, 0.256]Mixed Models Analysis