Asthma, Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL inhalation solution delivered by the Respimat® inhaler for four weeks in patients with chronic obstructive pulmonary disease (COPD). The selection of the optimum dose(s) will be based on bronchodilator efficacy (how well it helps your breathing), safety evaluations and pharmacokinetic evaluations (the amount of the medication found in your blood).
Interventions
DRUGBI 1744CL
Sponsors
Boehringer Ingelheim
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions 2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: Patients must have relatively stable, moderate to severe airway obstruction with a post-bronchodilator FEV1 30% of predicted normal and \< 80% of predicted normal and a post-bronchodilator FEV1 / FVC \< 70% at Visit 1 3. Male or female patients, 40 years of age or older 4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years. Patients who have never smoked cigarettes must be excluded 5. Patients must be able to perform technically acceptable pulmonary function tests and PEFR measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol 6. Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler (MDI).
Exclusion criteria
Selection of relevant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough FEV1 Response After 4 Weeks | Baseline and 4 weeks | Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough FEV1 Response After 2 Weeks | Baseline and 2 weeks | Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication. |
| Trough FVC Response After 1 Week | Baseline and 1 week | Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. |
| Trough FVC Response After 2 Weeks | Baseline and 2 weeks | Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. |
| Trough FVC Response After 4 Weeks | Baseline and 4 weeks | Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4 | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. |
| Peak FEV1 (0-3h) Response After 4 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed). |
| Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4 | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. |
| Peak FVC (0-3h) Response After 4 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks | Peak (0-3h) will be the maximum post-dose value during the first 3 hours. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at day 1 | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours postdose using the trapezoidal rule, divided by the observation time (3h) to report in litres. |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1 | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre 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 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 | 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2 | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre 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. |
| Peak FEV1 (0-3h) Response At Day 1 | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose at day 1 | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.Means are adjusted using a mixed effects model with baseline,treatment and centre (centre random, all other effects fixed). |
| Peak FEV1 (0-3h) Response After 1 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 week | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed). |
| 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 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed). |
| Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1 | baseline and day1 | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. |
| Trough FEV1 Response After 1 Week | Baseline and 1 week | Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication. |
| Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks | Baseline and 2 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. |
| Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks | Baseline and 4 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. |
| Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks | 4 weeks | Baseline PEFR was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment. |
| Weekly Mean Evening PEFR After 4 Weeks | 4 weeks | Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment. |
| Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 4 weeks | Weekly mean number of occasions of rescue therapy used per day (PRN salbutamol (albuterol)) |
| Area Under Curve From 0 to 3 Hours (AUC0-3) | Baseline and 4 weeks | AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3. |
| Maximum Concentration (Cmax) | Baseline and 4 weeks | Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma. |
| Time From Dosing to the Maximum Concentration (Tmax) | Baseline and 4 weeks | tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma. |
| Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Baseline and 4 weeks | AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3 at steady state. |
| Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Baseline and 4 weeks | AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=6 at steady state. |
| Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss) | Baseline and 4 weeks | AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=24 at steady state. |
| Maximum Concentration at Steady State (Cmax,ss) | Baseline and 4 weeks | Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state. |
| Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Baseline and 4 weeks | tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state. |
| Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | 4 weeks | Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events. |
| Laboratory Testing: Average Change From Baseline of Potassium | Baseline and day 29 | Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value. |
| Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week | Baseline and 1 week | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. |
Countries
Canada, Germany, Netherlands, United States
Participant flow
Pre-assignment details
409 patients were enrolled to the study, however 4 patients were assigned incorrect medication, so these patients were re-randomised, so only 405 patients actually started the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Placebo delivered by the Respimat Inhaler. | 79 |
| Olo 2 mcg qd Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler. | 81 |
| Olo 5 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler. | 80 |
| Olo 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler. | 86 |
| Olo 20 mcg qd Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler. | 79 |
| Total | 405 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 5 | 0 | 2 |
| Overall Study | Lack of Efficacy | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other reasons not listed above | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Olo 2 mcg qd | Olo 5 mcg qd | Olo 10 mcg qd | Olo 20 mcg qd | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 62.66 years STANDARD_DEVIATION 9.74 | 63.81 years STANDARD_DEVIATION 8.63 | 63.25 years STANDARD_DEVIATION 9.47 | 63.55 years STANDARD_DEVIATION 7.92 | 63.19 years STANDARD_DEVIATION 9 | 63.30 years STANDARD_DEVIATION 8.92 |
| Sex: Female, Male Female | 40 Participants | 39 Participants | 24 Participants | 35 Participants | 33 Participants | 171 Participants |
| Sex: Female, Male Male | 39 Participants | 42 Participants | 56 Participants | 51 Participants | 46 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 79 | 8 / 81 | 12 / 80 | 9 / 86 | 7 / 79 |
| serious Total, serious adverse events | 0 / 79 | 2 / 81 | 2 / 80 | 2 / 86 | 2 / 79 |
Outcome results
Primary
Trough FEV1 Response After 4 Weeks
Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.
Time frame: Baseline and 4 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 4 Weeks | -0.014 Liter | Standard Error 0.021 |
| Olo 2 mcg qd | Trough FEV1 Response After 4 Weeks | 0.046 Liter | Standard Error 0.021 |
| Olo 5 mcg qd | Trough FEV1 Response After 4 Weeks | 0.082 Liter | Standard Error 0.021 |
| Olo 10 mcg qd | Trough FEV1 Response After 4 Weeks | 0.109 Liter | Standard Error 0.021 |
| Olo 20 mcg qd | Trough FEV1 Response After 4 Weeks | 0.118 Liter | Standard Error 0.021 |
p-value: 0.023395% CI: [0.008, 0.113]ANCOVA
p-value: 0.000395% CI: [0.044, 0.149]ANCOVA
p-value: <0.000195% CI: [0.072, 0.175]ANCOVA
p-value: <0.000195% CI: [0.08, 0.185]ANCOVA
Secondary
Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)
AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=24 at steady state.
Time frame: Baseline and 4 weeks
Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 10 mcg qd | Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss) | Olodaterol | 104 Picogram*hours/milliliter | Geometric Coefficient of Variation 40.9 |
| Olo 10 mcg qd | Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss) | Olodaterol glucuronide | NA Picogram*hours/milliliter | — |
| Olo 20 mcg qd | Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss) | Olodaterol | 145 Picogram*hours/milliliter | Geometric Coefficient of Variation 55.1 |
| Olo 20 mcg qd | Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss) | Olodaterol glucuronide | NA Picogram*hours/milliliter | — |
Secondary
Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)
AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3 at steady state.
Time frame: Baseline and 4 weeks
Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 5 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol (N=0;0;0;63;70) | NA Picogram*hours/milliliter | — |
| Olo 5 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol glucuronide (N=0;0;55;69;63) | 9.29 Picogram*hours/milliliter | Geometric Coefficient of Variation 43.3 |
| Olo 10 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol (N=0;0;0;63;70) | 15.6 Picogram*hours/milliliter | Geometric Coefficient of Variation 49.9 |
| Olo 10 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol glucuronide (N=0;0;55;69;63) | 11.4 Picogram*hours/milliliter | Geometric Coefficient of Variation 69 |
| Olo 20 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol (N=0;0;0;63;70) | 27.7 Picogram*hours/milliliter | Geometric Coefficient of Variation 64.3 |
| Olo 20 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol glucuronide (N=0;0;55;69;63) | 23.9 Picogram*hours/milliliter | Geometric Coefficient of Variation 68.9 |
Secondary
Area Under Curve From 0 to 3 Hours (AUC0-3)
AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3.
Time frame: Baseline and 4 weeks
Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 10 mcg qd | Area Under Curve From 0 to 3 Hours (AUC0-3) | Olodaterol (N=0;0;0;29;58) | 13.3 Picogram*hours/milliliter | Geometric Coefficient of Variation 37.9 |
| Olo 10 mcg qd | Area Under Curve From 0 to 3 Hours (AUC0-3) | Olodaterol glucuronide (N=0;0;0;44;44) | 11.6 Picogram*hours/milliliter | Geometric Coefficient of Variation 52.8 |
| Olo 20 mcg qd | Area Under Curve From 0 to 3 Hours (AUC0-3) | Olodaterol (N=0;0;0;29;58) | 20.3 Picogram*hours/milliliter | Geometric Coefficient of Variation 56 |
| Olo 20 mcg qd | Area Under Curve From 0 to 3 Hours (AUC0-3) | Olodaterol glucuronide (N=0;0;0;44;44) | 21.1 Picogram*hours/milliliter | Geometric Coefficient of Variation 67.8 |
Secondary
Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=6 at steady state.
Time frame: Baseline and 4 weeks
Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 5 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol (N=0;0;0;55;69) | NA Picogram*hours/milliliter | — |
| Olo 5 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol glucuronide (N=0;0;32;50;48) | 21.4 Picogram*hours/milliliter | Geometric Coefficient of Variation 40.6 |
| Olo 10 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol (N=0;0;0;55;69) | 29.7 Picogram*hours/milliliter | Geometric Coefficient of Variation 43 |
| Olo 10 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol glucuronide (N=0;0;32;50;48) | 25.6 Picogram*hours/milliliter | Geometric Coefficient of Variation 60.2 |
| Olo 20 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol (N=0;0;0;55;69) | 46.4 Picogram*hours/milliliter | Geometric Coefficient of Variation 57.3 |
| Olo 20 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol glucuronide (N=0;0;32;50;48) | 49.4 Picogram*hours/milliliter | Geometric Coefficient of Variation 61 |
Secondary
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events.
Time frame: 4 weeks
Population: Treated set including all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Electrocardiogram QT prolonged | 0 participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Palpitations | 0 participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Tachycardia | 0 participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Gamma-glutamyltransferase increased | 0 participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Blood creatine phosphokinase increased | 0 participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Atrioventricular block first degree | 0 participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Sinus arrhythmia | 1 participants |
| Olo 2 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Sinus arrhythmia | 0 participants |
| Olo 2 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Atrioventricular block first degree | 0 participants |
| Olo 2 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Blood creatine phosphokinase increased | 0 participants |
| Olo 2 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Electrocardiogram QT prolonged | 1 participants |
| Olo 2 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Tachycardia | 0 participants |
| Olo 2 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Gamma-glutamyltransferase increased | 1 participants |
| Olo 2 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Palpitations | 1 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Atrioventricular block first degree | 0 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Electrocardiogram QT prolonged | 1 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Blood creatine phosphokinase increased | 0 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Gamma-glutamyltransferase increased | 0 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Sinus arrhythmia | 0 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Tachycardia | 1 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Palpitations | 0 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Gamma-glutamyltransferase increased | 0 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Sinus arrhythmia | 0 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Blood creatine phosphokinase increased | 0 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Palpitations | 0 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Tachycardia | 1 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Electrocardiogram QT prolonged | 0 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Atrioventricular block first degree | 0 participants |
| Olo 20 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Gamma-glutamyltransferase increased | 0 participants |
| Olo 20 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Palpitations | 0 participants |
| Olo 20 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Tachycardia | 0 participants |
| Olo 20 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Sinus arrhythmia | 0 participants |
| Olo 20 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Blood creatine phosphokinase increased | 1 participants |
| Olo 20 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Electrocardiogram QT prolonged | 2 participants |
| Olo 20 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Atrioventricular block first degree | 1 participants |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours postdose 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 first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at day 1
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| 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 at Day 1 | 0.031 Liter | Standard Error 0.017 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 0.165 Liter | Standard Error 0.017 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 0.203 Liter | Standard Error 0.017 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 0.236 Liter | Standard Error 0.017 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 0.234 Liter | Standard Error 0.017 |
p-value: <0.000195% CI: [0.09, 0.176]ANCOVA
p-value: <0.000195% CI: [0.128, 0.215]ANCOVA
p-value: <0.000195% CI: [0.162, 0.247]ANCOVA
p-value: <0.000195% CI: [0.159, 0.246]ANCOVA
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre 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 first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| 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 at Week 1 | -0.000 Liter | Standard Error 0.022 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 0.186 Liter | Standard Error 0.022 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 0.215 Liter | Standard Error 0.022 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 0.218 Liter | Standard Error 0.021 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 0.247 Liter | Standard Error 0.022 |
p-value: <0.000195% CI: [0.131, 0.243]ANCOVA
p-value: <0.000195% CI: [0.159, 0.271]ANCOVA
p-value: <0.000195% CI: [0.163, 0.273]ANCOVA
p-value: <0.000195% CI: [0.191, 0.304]ANCOVA
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre 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 first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| 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 at Week 2 | 0.006 Liter | Standard Error 0.024 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 | 0.166 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 at Week 2 | 0.200 Liter | Standard Error 0.024 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 | 0.209 Liter | Standard Error 0.023 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 | 0.211 Liter | Standard Error 0.024 |
p-value: <0.000195% CI: [0.1, 0.219]ANCOVA
p-value: <0.000195% CI: [0.134, 0.253]ANCOVA
p-value: <0.000195% CI: [0.144, 0.262]ANCOVA
p-value: <0.000195% CI: [0.145, 0.264]ANCOVA
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.013 Liter | Standard Error 0.025 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.154 Liter | Standard Error 0.024 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.175 Liter | Standard Error 0.025 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.226 Liter | Standard Error 0.024 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.228 Liter | Standard Error 0.025 |
p-value: <0.000195% CI: [0.078, 0.204]ANCOVA
p-value: <0.000195% CI: [0.099, 0.225]ANCOVA
p-value: <0.000195% CI: [0.151, 0.275]ANCOVA
p-value: <0.000195% CI: [0.151, 0.277]ANCOVA
Secondary
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Time frame: Baseline and 1 week
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week | -0.018 Liter | Standard Error 0.03 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week | 0.067 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week | 0.156 Liter | Standard Error 0.029 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week | 0.132 Liter | Standard Error 0.03 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week | 0.118 Liter | Standard Error 0.03 |
p-value: 0.030995% CI: [0.008, 0.162]ANCOVA
p-value: <0.000195% CI: [0.098, 0.25]ANCOVA
p-value: 0.000295% CI: [0.072, 0.228]ANCOVA
p-value: 0.000695% CI: [0.059, 0.214]ANCOVA
Secondary
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Time frame: Baseline and 2 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks | 0.006 Liter | Standard Error 0.031 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks | 0.059 Liter | Standard Error 0.031 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks | 0.135 Liter | Standard Error 0.03 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks | 0.105 Liter | Standard Error 0.031 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks | 0.098 Liter | Standard Error 0.031 |
p-value: 0.21595% CI: [-0.031, 0.137]ANCOVA
p-value: 0.002495% CI: [0.046, 0.212]ANCOVA
p-value: 0.02395% CI: [0.014, 0.184]ANCOVA
p-value: 0.033395% CI: [0.007, 0.177]ANCOVA
Secondary
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Time frame: Baseline and 4 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks | 0.005 Liter | Standard Error 0.031 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks | 0.058 Liter | Standard Error 0.031 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks | 0.134 Liter | Standard Error 0.03 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks | 0.145 Liter | Standard Error 0.032 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks | 0.094 Liter | Standard Error 0.031 |
p-value: 0.215895% CI: [-0.031, 0.137]ANCOVA
p-value: 0.002495% CI: [0.046, 0.212]ANCOVA
p-value: 0.001395% CI: [0.055, 0.225]ANCOVA
p-value: 0.037695% CI: [0.005, 0.174]ANCOVA
Secondary
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Time frame: baseline and day1
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1 | 0.019 Liter | Standard Error 0.028 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1 | 0.064 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1 | 0.166 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1 | 0.195 Liter | Standard Error 0.028 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1 | 0.171 Liter | Standard Error 0.028 |
p-value: 0.239295% CI: [-0.03, 0.121]ANCOVA
p-value: 0.000195% CI: [0.072, 0.222]ANCOVA
p-value: <0.000195% CI: [0.099, 0.253]ANCOVA
p-value: 0.000195% CI: [0.076, 0.228]ANCOVA
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.009 Liter | Standard Error 0.044 |
| Olo 2 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.271 Liter | Standard Error 0.043 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.292 Liter | Standard Error 0.044 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.320 Liter | Standard Error 0.042 |
| Olo 20 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.313 Liter | Standard Error 0.044 |
p-value: <0.000195% CI: [0.15, 0.373]ANCOVA
p-value: <0.000195% CI: [0.171, 0.395]ANCOVA
p-value: <0.000195% CI: [0.201, 0.421]ANCOVA
p-value: <0.000195% CI: [0.192, 0.416]ANCOVA
Secondary
Laboratory Testing: Average Change From Baseline of Potassium
Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value.
Time frame: Baseline and day 29
Population: Treated set includes all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Laboratory Testing: Average Change From Baseline of Potassium | 0.97 mmol/L |
| Olo 2 mcg qd | Laboratory Testing: Average Change From Baseline of Potassium | 0.99 mmol/L |
| Olo 5 mcg qd | Laboratory Testing: Average Change From Baseline of Potassium | 0.98 mmol/L |
| Olo 10 mcg qd | Laboratory Testing: Average Change From Baseline of Potassium | 0.97 mmol/L |
| Olo 20 mcg qd | Laboratory Testing: Average Change From Baseline of Potassium | 0.98 mmol/L |
Secondary
Maximum Concentration at Steady State (Cmax,ss)
Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.
Time frame: Baseline and 4 weeks
Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 5 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol (N=0;0;46;72;72) | 4.02 Picogram/milliliter | Geometric Coefficient of Variation 46.7 |
| Olo 5 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol glucuronide (N=0;0;60;72;66) | 4.90 Picogram/milliliter | Geometric Coefficient of Variation 49.8 |
| Olo 10 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol (N=0;0;46;72;72) | 7.13 Picogram/milliliter | Geometric Coefficient of Variation 63.8 |
| Olo 10 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol glucuronide (N=0;0;60;72;66) | 5.55 Picogram/milliliter | Geometric Coefficient of Variation 65.2 |
| Olo 20 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol (N=0;0;46;72;72) | 14.1 Picogram/milliliter | Geometric Coefficient of Variation 83.4 |
| Olo 20 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol glucuronide (N=0;0;60;72;66) | 11.1 Picogram/milliliter | Geometric Coefficient of Variation 81 |
Secondary
Maximum Concentration (Cmax)
Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma.
Time frame: Baseline and 4 weeks
Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 5 mcg qd | Maximum Concentration (Cmax) | Olodaterol (N=0;0;40;71;69) | 3.58 Picogram/milliliter | Geometric Coefficient of Variation 51.4 |
| Olo 5 mcg qd | Maximum Concentration (Cmax) | Olodaterol glucuronide (N=0;0;54;71;66) | 3.94 Picogram/milliliter | Geometric Coefficient of Variation 97.5 |
| Olo 10 mcg qd | Maximum Concentration (Cmax) | Olodaterol (N=0;0;40;71;69) | 5.45 Picogram/milliliter | Geometric Coefficient of Variation 63.5 |
| Olo 10 mcg qd | Maximum Concentration (Cmax) | Olodaterol glucuronide (N=0;0;54;71;66) | 5.24 Picogram/milliliter | Geometric Coefficient of Variation 97.4 |
| Olo 20 mcg qd | Maximum Concentration (Cmax) | Olodaterol (N=0;0;40;71;69) | 12.2 Picogram/milliliter | Geometric Coefficient of Variation 76 |
| Olo 20 mcg qd | Maximum Concentration (Cmax) | Olodaterol glucuronide (N=0;0;54;71;66) | 10.6 Picogram/milliliter | Geometric Coefficient of Variation 88.1 |
Secondary
Peak FEV1 (0-3h) Response After 1 Weeks
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 week
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 1 Weeks | 0.062 Liter | Standard Error 0.024 |
| Olo 2 mcg qd | Peak FEV1 (0-3h) Response After 1 Weeks | 0.264 Liter | Standard Error 0.023 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 1 Weeks | 0.293 Liter | Standard Error 0.024 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 1 Weeks | 0.295 Liter | Standard Error 0.023 |
| Olo 20 mcg qd | Peak FEV1 (0-3h) Response After 1 Weeks | 0.321 Liter | Standard Error 0.024 |
p-value: <0.000195% CI: [0.169, 0.294]ANCOVA
p-value: <0.000195% CI: [0.172, 0.295]ANCOVA
p-value: <0.000195% CI: [0.197, 0.322]ANCOVA
p-value: <0.000195% CI: [0.14, 0.264]ANCOVA
Secondary
Peak FEV1 (0-3h) Response After 2 Weeks
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 2 Weeks | 0.079 Liter | Standard Error 0.025 |
| Olo 2 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.243 Liter | Standard Error 0.025 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.267 Liter | Standard Error 0.025 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.282 Liter | Standard Error 0.024 |
| Olo 20 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.280 Liter | Standard Error 0.025 |
p-value: <0.000195% CI: [0.101, 0.228]ANCOVA
p-value: <0.000195% CI: [0.125, 0.252]ANCOVA
p-value: <0.000195% CI: [0.14, 0.266]ANCOVA
p-value: <0.000195% CI: [0.137, 0.265]ANCOVA
Secondary
Peak FEV1 (0-3h) Response After 4 Weeks
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response After 4 Weeks | 0.078 Liter | Standard Error 0.026 |
| Olo 2 mcg qd | Peak FEV1 (0-3h) Response After 4 Weeks | 0.242 Liter | Standard Error 0.026 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 4 Weeks | 0.247 Liter | Standard Error 0.026 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 4 Weeks | 0.295 Liter | Standard Error 0.025 |
| Olo 20 mcg qd | Peak FEV1 (0-3h) Response After 4 Weeks | 0.303 Liter | Standard Error 0.026 |
p-value: <0.000195% CI: [0.097, 0.231]ANCOVA
p-value: <0.000195% CI: [0.102, 0.237]ANCOVA
p-value: <0.000195% CI: [0.152, 0.284]ANCOVA
p-value: <0.000195% CI: [0.157, 0.292]ANCOVA
Secondary
Peak FEV1 (0-3h) Response At Day 1
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.Means are adjusted using a mixed effects model with baseline,treatment and centre (centre random, all other effects fixed).
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose at day 1
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 (0-3h) Response At Day 1 | 0.104 Liter | Standard Error 0.021 |
| Olo 2 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.259 Liter | Standard Error 0.021 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.288 Liter | Standard Error 0.021 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.335 Liter | Standard Error 0.02 |
| Olo 20 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.335 Liter | Standard Error 0.021 |
p-value: <0.000195% CI: [0.101, 0.209]ANCOVA
p-value: <0.000195% CI: [0.131, 0.239]ANCOVA
p-value: <0.000195% CI: [0.178, 0.284]ANCOVA
p-value: <0.000195% CI: [0.177, 0.286]ANCOVA
Secondary
Peak FVC (0-3h) Response After 4 Weeks
Peak (0-3h) will be the maximum post-dose value during the first 3 hours. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.
Time frame: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FVC (0-3h) Response After 4 Weeks | 0.152 Liter | Standard Error 0.046 |
| Olo 2 mcg qd | Peak FVC (0-3h) Response After 4 Weeks | 0.440 Liter | Standard Error 0.046 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 4 Weeks | 0.432 Liter | Standard Error 0.046 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 4 Weeks | 0.449 Liter | Standard Error 0.044 |
| Olo 20 mcg qd | Peak FVC (0-3h) Response After 4 Weeks | 0.438 Liter | Standard Error 0.046 |
p-value: <0.000195% CI: [0.167, 0.409]ANCOVA
p-value: <0.000195% CI: [0.159, 0.401]ANCOVA
p-value: <0.000195% CI: [0.178, 0.416]ANCOVA
p-value: <0.000195% CI: [0.164, 0.407]ANCOVA
Secondary
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.
Time frame: Baseline and 4 weeks
Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Olo 5 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol (N=0;0;46;72;72) | 0.192 hours |
| Olo 5 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol glucuronide (N=0;0;60;72;66) | 3.00 hours |
| Olo 10 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol (N=0;0;46;72;72) | 0.200 hours |
| Olo 10 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol glucuronide (N=0;0;60;72;66) | 3.00 hours |
| Olo 20 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol (N=0;0;46;72;72) | 0.200 hours |
| Olo 20 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol glucuronide (N=0;0;60;72;66) | 3.00 hours |
Secondary
Time From Dosing to the Maximum Concentration (Tmax)
tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma.
Time frame: Baseline and 4 weeks
Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Olo 5 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol (N=0;0;40;71;69) | 0.167 hours |
| Olo 5 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol glucuronide (N=0;0;54;71;66) | 2.95 hours |
| Olo 10 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol (N=0;0;40;71;69) | 0.183 hours |
| Olo 10 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol glucuronide (N=0;0;54;71;66) | 3.00 hours |
| Olo 20 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol (N=0;0;40;71;69) | 0.200 hours |
| Olo 20 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol glucuronide (N=0;0;54;71;66) | 3.00 hours |
Secondary
Trough FEV1 Response After 1 Week
Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.
Time frame: Baseline and 1 week
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 1 Week | -0.029 Liter | Standard Error 0.019 |
| Olo 2 mcg qd | Trough FEV1 Response After 1 Week | 0.059 Liter | Standard Error 0.018 |
| Olo 5 mcg qd | Trough FEV1 Response After 1 Week | 0.108 Liter | Standard Error 0.019 |
| Olo 10 mcg qd | Trough FEV1 Response After 1 Week | 0.099 Liter | Standard Error 0.018 |
| Olo 20 mcg qd | Trough FEV1 Response After 1 Week | 0.140 Liter | Standard Error 0.019 |
p-value: 0.000495% CI: [0.039, 0.137]ANCOVA
p-value: <0.000195% CI: [0.088, 0.186]ANCOVA
p-value: <0.000195% CI: [0.08, 0.176]ANCOVA
p-value: <0.000195% CI: [0.12, 0.218]ANCOVA
Secondary
Trough FEV1 Response After 2 Weeks
Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.
Time frame: Baseline and 2 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response After 2 Weeks | -0.023 Liter | Standard Error 0.02 |
| Olo 2 mcg qd | Trough FEV1 Response After 2 Weeks | 0.062 Liter | Standard Error 0.02 |
| Olo 5 mcg qd | Trough FEV1 Response After 2 Weeks | 0.099 Liter | Standard Error 0.02 |
| Olo 10 mcg qd | Trough FEV1 Response After 2 Weeks | 0.102 Liter | Standard Error 0.02 |
| Olo 20 mcg qd | Trough FEV1 Response After 2 Weeks | 0.105 Liter | Standard Error 0.02 |
p-value: 0.001195% CI: [0.034, 0.136]ANCOVA
p-value: <0.000195% CI: [0.07, 0.173]ANCOVA
p-value: <0.000195% CI: [0.075, 0.175]ANCOVA
p-value: <0.000195% CI: [0.077, 0.179]ANCOVA
Secondary
Trough FVC Response After 1 Week
Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.
Time frame: Baseline and 1 week
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 1 Week | -0.020 Liter | Standard Error 0.033 |
| Olo 2 mcg qd | Trough FVC Response After 1 Week | 0.090 Liter | Standard Error 0.033 |
| Olo 5 mcg qd | Trough FVC Response After 1 Week | 0.154 Liter | Standard Error 0.033 |
| Olo 10 mcg qd | Trough FVC Response After 1 Week | 0.149 Liter | Standard Error 0.032 |
| Olo 20 mcg qd | Trough FVC Response After 1 Week | 0.151 Liter | Standard Error 0.033 |
p-value: 0.012795% CI: [0.024, 0.197]ANCOVA
p-value: <0.000195% CI: [0.087, 0.261]ANCOVA
p-value: 0.000195% CI: [0.084, 0.255]ANCOVA
p-value: 0.000195% CI: [0.084, 0.258]ANCOVA
Secondary
Trough FVC Response After 2 Weeks
Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.
Time frame: Baseline and 2 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 2 Weeks | -0.000 Liter | Standard Error 0.04 |
| Olo 2 mcg qd | Trough FVC Response After 2 Weeks | 0.090 Liter | Standard Error 0.04 |
| Olo 5 mcg qd | Trough FVC Response After 2 Weeks | 0.171 Liter | Standard Error 0.04 |
| Olo 10 mcg qd | Trough FVC Response After 2 Weeks | 0.149 Liter | Standard Error 0.039 |
| Olo 20 mcg qd | Trough FVC Response After 2 Weeks | 0.148 Liter | Standard Error 0.04 |
p-value: 0.083695% CI: [-0.012, 0.192]ANCOVA
p-value: 0.001195% CI: [0.068, 0.274]ANCOVA
p-value: 0.003795% CI: [0.049, 0.25]ANCOVA
p-value: 0.004795% CI: [0.046, 0.251]ANCOVA
Secondary
Trough FVC Response After 4 Weeks
Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.
Time frame: Baseline and 4 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response After 4 Weeks | -0.026 Liter | Standard Error 0.04 |
| Olo 2 mcg qd | Trough FVC Response After 4 Weeks | 0.068 Liter | Standard Error 0.04 |
| Olo 5 mcg qd | Trough FVC Response After 4 Weeks | 0.136 Liter | Standard Error 0.04 |
| Olo 10 mcg qd | Trough FVC Response After 4 Weeks | 0.146 Liter | Standard Error 0.039 |
| Olo 20 mcg qd | Trough FVC Response After 4 Weeks | 0.153 Liter | Standard Error 0.04 |
p-value: 0.069595% CI: [-0.008, 0.195]ANCOVA
p-value: 0.001895% CI: [0.061, 0.264]ANCOVA
p-value: 0.000895% CI: [0.072, 0.272]ANCOVA
p-value: 0.000695% CI: [0.077, 0.281]ANCOVA
Secondary
Weekly Mean Evening PEFR After 4 Weeks
Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment.
Time frame: 4 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weekly Mean Evening PEFR After 4 Weeks | 224.65 Liter/minute | Standard Error 4.581 |
| Olo 2 mcg qd | Weekly Mean Evening PEFR After 4 Weeks | 235.09 Liter/minute | Standard Error 4.507 |
| Olo 5 mcg qd | Weekly Mean Evening PEFR After 4 Weeks | 246.98 Liter/minute | Standard Error 4.621 |
| Olo 10 mcg qd | Weekly Mean Evening PEFR After 4 Weeks | 262.88 Liter/minute | Standard Error 4.376 |
| Olo 20 mcg qd | Weekly Mean Evening PEFR After 4 Weeks | 250.06 Liter/minute | Standard Error 4.678 |
p-value: 0.097395% CI: [-1.911, 22.803]ANCOVA
p-value: 0.000595% CI: [9.824, 34.842]ANCOVA
p-value: <0.000195% CI: [26.054, 50.409]ANCOVA
p-value: <0.000195% CI: [12.814, 38.002]ANCOVA
Secondary
Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks
Weekly mean number of occasions of rescue therapy used per day (PRN salbutamol (albuterol))
Time frame: 4 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 2.914 Number of puffs | Standard Error 0.26 |
| Olo 2 mcg qd | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 2.393 Number of puffs | Standard Error 0.255 |
| Olo 5 mcg qd | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 3.052 Number of puffs | Standard Error 0.258 |
| Olo 10 mcg qd | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 1.949 Number of puffs | Standard Error 0.248 |
| Olo 20 mcg qd | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 2.500 Number of puffs | Standard Error 0.262 |
p-value: 0.154195% CI: [-1.237, 0.196]ANCOVA
p-value: 0.706595% CI: [-0.583, 0.859]ANCOVA
p-value: 0.007695% CI: [-1.671, -0.258]ANCOVA
p-value: 0.262695% CI: [-1.138, 0.311]ANCOVA
Secondary
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks
Baseline PEFR was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment.
Time frame: 4 weeks
Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks | 212.69 Liter/minute | Standard Error 4.431 |
| Olo 2 mcg qd | Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks | 226.39 Liter/minute | Standard Error 4.367 |
| Olo 5 mcg qd | Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks | 233.97 Liter/minute | Standard Error 4.425 |
| Olo 10 mcg qd | Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks | 250.77 Liter/minute | Standard Error 4.244 |
| Olo 20 mcg qd | Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks | 235.75 Liter/minute | Standard Error 4.471 |
p-value: 0.021195% CI: [2.07, 25.34]ANCOVA
p-value: 0.000495% CI: [9.581, 32.99]ANCOVA
p-value: <0.000195% CI: [26.607, 49.546]ANCOVA
p-value: 0.000195% CI: [11.282, 34.845]ANCOVA