Asthma
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 asthma. 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 1744 CL
Sponsors
Boehringer Ingelheim
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 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. Male or female patients, 18 years of age or older 3. Diagnosis of asthma (GINA) 4. Pre-bronchodilator FEV1 greater than or equal to 60% predicted and \<90% predicted (ECSC); 5. Increase in FEV1 greater than or equal to 12% and 200 ml 15 minutes after 400µg salbutamol (albuterol) at Visit 1 6. Patient must have been taking Inhaled Corticosteroids for at least 12 weeks prior to screening, and must have been receiving a stable low/moderate dose for at least 6 weeks prior to screening. 7. Patients must be able to perform technically acceptable pulmonary function tests and PEF measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol 8. Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler (MDI).
Exclusion criteria
1. Patients with a smoking history of more than 10 pack years 2. Patients with any of the following conditions: a diagnosis of thyrotoxicosis, a diagnosis of paroxysmal tachycardia (\>100 beats per minute), a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms), a history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) 3. Patients with any of the following conditions: a history of myocardial infarction within 1 year of screening visit (Visit 1), a diagnosis of clinically relevant cardiac arrhythmia, a history of cor pulmonale, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed), a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, a history of significant alcohol or drug abuse 4. Patients who have undergone thoracotomy with pulmonary resection 5. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1) 6. Pregnant or nursing women 7. Women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least 2 years 8. Patients who have previously been randomized in this study or are currently participating in another study 9. Patients who are unable to comply with pulmonary medication restrictions prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough FEV1 Response After 4 Weeks | Baseline and 4 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough FEV1 Response After 1 Week | Baseline and 1 week | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval. |
| Trough FEV1 Response After 2 Weeks | Baseline and 2 weeks | Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval. |
| Trough FVC Response After 1 Week | Baseline and 1 week | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval. |
| Trough FVC Response After 2 Weeks | Baseline and 2 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval. |
| Trough FVC Response After 4 Weeks | Baseline and 4 weeks | Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval. |
| 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. 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. |
| 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. 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. |
| 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. 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 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. 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. 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 4 | 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 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. 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. |
| Peak FEV1 (0-3h) Response After 1 Week | 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. |
| 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. |
| 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. |
| Peak FVC (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 after 1 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. |
| Peak FVC (0-3h) Response After 1 Week | 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 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. |
| Weekly Mean Pre-dose Morning PEFR After 4 Weeks | Baseline and 4 weeks | Response was defined as change from baseline. Baseline peak expiratory flow response (PEFR) was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment. |
| 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 | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. |
| Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4 | 1 hour (h) prior to dose on first day of randomized treatment (baseline) and 1h, 3h, 6h, 9h, 12h 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. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. |
| Weekly Mean Evening PEFR After 4 Weeks | Baseline and 4 weeks | Response was defined as change from baseline. Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment. |
| PEFR Variability After 4 Weeks | 4 weeks | PEFR variability represents the absolute difference between the highest morning PEFR value and the highest evening PEFR value of 1 day, divided by the arithmetic mean of these 2 PEFR values and expressed as a percent, weekly means. |
| 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 \[albuterol\]) as assessed by the e-Diary (e-Diary incorporated in AM2+). |
| Area Under Curve From 0 to 3 Hours (AUC0-3) | 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration | AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=3 |
| Maximum Concentration (Cmax) | 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration | Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma. |
| Time From Dosing to the Maximum Concentration (Tmax) | 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration | tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma. |
| Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration | AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) 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) | 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration | AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) 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) | 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration | AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=24 at steady state. |
| Maximum Concentration at Steady State (Cmax,ss) | 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration | Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state. |
| Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration | tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state. |
| Total Score in Asthma Control Questionnaire After 4 Weeks | 4 weeks | Adequacy of asthma control was assessed using a scale of: 0=totally controlled, to 6=Severely uncontrolled. |
| 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 29 days | Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value. |
| Peak FVC (0-3h) Response After 2 Weeks | 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 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 FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. |
Countries
Canada, France, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Placebo delivered by the Respimat Inhaler. | 54 |
| Olo 2 mcg qd Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler. | 61 |
| Olo 5 mcg qd Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler. | 60 |
| Olo 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler. | 60 |
| Olo 20 mcg qd Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler. | 61 |
| Total | 296 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Olo 2 mcg qd | Olo 5 mcg qd | Olo 10 mcg qd | Olo 20 mcg qd |
|---|---|---|---|---|---|---|
| Age, Continuous | 45.23 years STANDARD_DEVIATION 13.88 | 43.59 years STANDARD_DEVIATION 14.11 | 45.36 years STANDARD_DEVIATION 15.12 | 46.17 years STANDARD_DEVIATION 12.96 | 46.25 years STANDARD_DEVIATION 14.45 | 44.62 years STANDARD_DEVIATION 12.95 |
| Sex: Female, Male Female | 170 Participants | 34 Participants | 39 Participants | 30 Participants | 34 Participants | 33 Participants |
| Sex: Female, Male Male | 126 Participants | 20 Participants | 22 Participants | 30 Participants | 26 Participants | 28 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 | 9 / 54 | 9 / 61 | 11 / 60 | 7 / 60 | 11 / 61 |
| serious Total, serious adverse events | 0 / 54 | 0 / 61 | 0 / 60 | 1 / 60 | 1 / 61 |
Outcome results
Primary
Trough FEV1 Response After 4 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.
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 | 0.004 Liter | Standard Error 0.034 |
| Olo 2 mcg qd | Trough FEV1 Response After 4 Weeks | 0.083 Liter | Standard Error 0.032 |
| Olo 5 mcg qd | Trough FEV1 Response After 4 Weeks | 0.090 Liter | Standard Error 0.032 |
| Olo 10 mcg qd | Trough FEV1 Response After 4 Weeks | 0.080 Liter | Standard Error 0.032 |
| Olo 20 mcg qd | Trough FEV1 Response After 4 Weeks | 0.150 Liter | Standard Error 0.032 |
p-value: 0.075495% CI: [-0.008, 0.167]Mixed Models Analysis
p-value: 0.057195% CI: [-0.003, 0.174]Mixed Models Analysis
p-value: 0.090695% CI: [-0.012, 0.164]Mixed Models Analysis
p-value: 0.001195% CI: [0.059, 0.234]Mixed Models Analysis
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 (a metabolite of olodaterol) in plasma from 0 to time t=24 at steady state.
Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
Population: All evaluable patients were included in the pharmacokinetic (PK) analysis. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of PK parameters 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 | 83.7 Picogram*hours/milliliter | Geometric Coefficient of Variation 30.3 |
| 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 glucuronide | NA Picogram*hours/milliliter | — |
| Olo 20 mcg qd | Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss) | Olodaterol | 147 Picogram*hours/milliliter | Geometric Coefficient of Variation 49.5 |
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 (a metabolite of olodaterol) in plasma from 0 to time t=3 at steady state.
Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
Population: All evaluable patients were included in the pharmacokinetic (PK) analysis. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of PK parameters 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;38;53) | 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;38;44;54) | 7.71 Picogram*hours/milliliter | Geometric Coefficient of Variation 62.2 |
| Olo 10 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol (N=0;0;0;38;53) | 13.0 Picogram*hours/milliliter | Geometric Coefficient of Variation 42.7 |
| Olo 10 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol glucuronide (N=0;0;38;44;54) | 9.04 Picogram*hours/milliliter | Geometric Coefficient of Variation 64.2 |
| Olo 20 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol glucuronide (N=0;0;38;44;54) | 19.0 Picogram*hours/milliliter | Geometric Coefficient of Variation 59.4 |
| Olo 20 mcg qd | Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) | Olodaterol (N=0;0;0;38;53) | 25.5 Picogram*hours/milliliter | Geometric Coefficient of Variation 56.5 |
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 (a metabolite of olodaterol) in plasma from 0 to time t=3
Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration
Population: All evaluable patients were included in the pharmacokinetic (PK) analysis. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of PK parameters 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;20;44) | 11.8 Picogram*hours/milliliter | Geometric Coefficient of Variation 35.2 |
| Olo 10 mcg qd | Area Under Curve From 0 to 3 Hours (AUC0-3) | Olodaterol glucuronide (N=0;0;0;28;36) | 9.14 Picogram*hours/milliliter | Geometric Coefficient of Variation 48.6 |
| Olo 20 mcg qd | Area Under Curve From 0 to 3 Hours (AUC0-3) | Olodaterol (N=0;0;0;20;44) | 17.8 Picogram*hours/milliliter | Geometric Coefficient of Variation 42.1 |
| Olo 20 mcg qd | Area Under Curve From 0 to 3 Hours (AUC0-3) | Olodaterol glucuronide (N=0;0;0;28;36) | 20.3 Picogram*hours/milliliter | Geometric Coefficient of Variation 48 |
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 (a metabolite of olodaterol) in plasma from 0 to time t=6 at steady state.
Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
Population: All evaluable patients were included in the pharmacokinetic (PK) analysis. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of PK parameters 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;32;50) | 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;21;23;33) | 19.2 Picogram*hours/milliliter | Geometric Coefficient of Variation 58.2 |
| Olo 10 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol (N=0;0;0;32;50) | 25.3 Picogram*hours/milliliter | Geometric Coefficient of Variation 35.7 |
| Olo 10 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol glucuronide (N=0;0;21;23;33) | 21.3 Picogram*hours/milliliter | Geometric Coefficient of Variation 56.4 |
| Olo 20 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol glucuronide (N=0;0;21;23;33) | 37.6 Picogram*hours/milliliter | Geometric Coefficient of Variation 54.2 |
| Olo 20 mcg qd | Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) | Olodaterol (N=0;0;0;32;50) | 46.3 Picogram*hours/milliliter | Geometric Coefficient of Variation 50.3 |
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 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 | Ventricular extrasystoles | 0 participants |
| Placebo | 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 | Palpitations | 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 | Ventricular extrasystoles | 0 participants |
| Olo 5 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 | Blood creatine phosphokinase increased | 0 participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Ventricular extrasystoles | 1 participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Ventricular extrasystoles | 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 | Blood creatine phosphokinase increased | 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 | Palpitations | 2 participants |
| Olo 20 mcg qd | Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination | Ventricular extrasystoles | 0 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. 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 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 | 0.092 Liter | Standard Error 0.03 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 0.271 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 0.275 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 0.265 Liter | Standard Error 0.028 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 | 0.383 Liter | Standard Error 0.028 |
p-value: <0.000195% CI: [0.102, 0.255]Mixed Models Analysis
p-value: <0.000195% CI: [0.106, 0.26]Mixed Models Analysis
p-value: <0.000195% CI: [0.096, 0.25]Mixed Models Analysis
p-value: <0.000195% CI: [0.214, 0.367]Mixed Models Analysis
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. 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 | 0.062 Liter | Standard Error 0.034 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 0.252 Liter | Standard Error 0.032 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 0.258 Liter | Standard Error 0.033 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 0.219 Liter | Standard Error 0.032 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 | 0.325 Liter | Standard Error 0.032 |
p-value: <0.000195% CI: [0.101, 0.279]Mixed Models Analysis
p-value: <0.000195% CI: [0.107, 0.286]Mixed Models Analysis
p-value: 0.000795% CI: [0.067, 0.246]Mixed Models Analysis
p-value: <0.000195% CI: [0.174, 0.352]Mixed Models Analysis
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. 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 | 0.084 Liter | Standard Error 0.038 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 | 0.298 Liter | Standard Error 0.036 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 | 0.240 Liter | Standard Error 0.036 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 | 0.172 Liter | Standard Error 0.036 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 | 0.311 Liter | Standard Error 0.035 |
p-value: <0.000195% CI: [0.115, 0.313]Mixed Models Analysis
p-value: 0.002195% CI: [0.057, 0.255]Mixed Models Analysis
p-value: 0.079595% CI: [-0.01, 0.187]Mixed Models Analysis
p-value: <0.000195% CI: [0.129, 0.326]Mixed Models Analysis
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) 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. 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 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 0-3 h (AUC 0-3h) Response at Week 4 | 0.092 Liter | Standard Error 0.037 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4 | 0.271 Liter | Standard Error 0.035 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4 | 0.224 Liter | Standard Error 0.035 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4 | 0.192 Liter | Standard Error 0.035 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4 | 0.332 Liter | Standard Error 0.035 |
p-value: 0.000395% CI: [0.082, 0.276]Mixed Models Analysis
p-value: 0.007795% CI: [0.035, 0.229]Mixed Models Analysis
p-value: 0.042795% CI: [0.003, 0.197]Mixed Models Analysis
p-value: <0.000195% CI: [0.143, 0.336]Mixed Models Analysis
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. 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 | 0.091 Liter | Standard Error 0.037 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.269 Liter | Standard Error 0.035 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.229 Liter | Standard Error 0.035 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.190 Liter | Standard Error 0.035 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.323 Liter | Standard Error 0.035 |
p-value: 0.000595% CI: [0.079, 0.277]Mixed Models Analysis
p-value: 0.00795% CI: [0.038, 0.237]Mixed Models Analysis
p-value: 0.051295% CI: [-0.001, 0.198]Mixed Models Analysis
p-value: <0.000195% CI: [0.133, 0.331]Mixed Models Analysis
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) 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. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time frame: 1 hour (h) prior to dose on first day of randomized treatment (baseline) and 1h, 3h, 6h, 9h, 12h 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 6-12 h (AUC 6-12h) Response at Week 4 | 0.054 Liter | Standard Error 0.051 |
| Olo 2 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4 | 0.107 Liter | Standard Error 0.048 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4 | 0.098 Liter | Standard Error 0.049 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4 | 0.092 Liter | Standard Error 0.049 |
| Olo 20 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4 | 0.216 Liter | Standard Error 0.049 |
p-value: 0.433195% CI: [-0.079, 0.184]Mixed Models Analysis
p-value: 0.51595% CI: [-0.089, 0.178]Mixed Models Analysis
p-value: 0.571495% CI: [-0.095, 0.171]Mixed Models Analysis
p-value: 0.017795% CI: [0.028, 0.296]Mixed Models Analysis
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. 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 | 0.076 Liter | Standard Error 0.045 |
| Olo 2 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.159 Liter | Standard Error 0.042 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.154 Liter | Standard Error 0.043 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.113 Liter | Standard Error 0.043 |
| Olo 20 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 | 0.267 Liter | Standard Error 0.042 |
p-value: 0.181195% CI: [-0.039, 0.203]Mixed Models Analysis
p-value: 0.211895% CI: [-0.044, 0.199]Mixed Models Analysis
p-value: 0.550495% CI: [-0.085, 0.158]Mixed Models Analysis
p-value: 0.002295% CI: [0.069, 0.312]Mixed Models Analysis
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 29 days
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Laboratory Testing: Average Change From Baseline of Potassium | 0.98 mmol/L |
| Olo 2 mcg qd | Laboratory Testing: Average Change From Baseline of Potassium | 0.97 mmol/L |
| Olo 5 mcg qd | Laboratory Testing: Average Change From Baseline of Potassium | 1.00 mmol/L |
| Olo 10 mcg qd | Laboratory Testing: Average Change From Baseline of Potassium | 0.99 mmol/L |
| Olo 20 mcg qd | Laboratory Testing: Average Change From Baseline of Potassium | 0.97 mmol/L |
Secondary
Maximum Concentration at Steady State (Cmax,ss)
Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state.
Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
Population: All evaluable patients were included in the pharmacokinetic (PK) analysis. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of PK parameters 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;39;45;56) | 3.19 Picogram/milliliter | Geometric Coefficient of Variation 35 |
| Olo 5 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol glucuronide N=(0;0;46;46;54) | 4.16 Picogram/milliliter | Geometric Coefficient of Variation 46.8 |
| Olo 10 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol N=(0;0;39;45;56) | 5.09 Picogram/milliliter | Geometric Coefficient of Variation 53 |
| Olo 10 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol glucuronide N=(0;0;46;46;54) | 5.04 Picogram/milliliter | Geometric Coefficient of Variation 57.4 |
| Olo 20 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol N=(0;0;39;45;56) | 12.1 Picogram/milliliter | Geometric Coefficient of Variation 69.2 |
| Olo 20 mcg qd | Maximum Concentration at Steady State (Cmax,ss) | Olodaterol glucuronide N=(0;0;46;46;54) | 9.19 Picogram/milliliter | Geometric Coefficient of Variation 53.6 |
Secondary
Maximum Concentration (Cmax)
Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.
Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration
Population: All evaluable patients were included in the pharmacokinetic (PK) analysis. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of PK parameters or had insufficient data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 5 mcg qd | Maximum Concentration (Cmax) | Olodaterol (N=0;0;21;44;58) | 3.54 Picogram/milliliter | Geometric Coefficient of Variation 48.4 |
| Olo 5 mcg qd | Maximum Concentration (Cmax) | Olodaterol glucuronide (N=0;0;38;54;57) | 3.57 Picogram/milliliter | Geometric Coefficient of Variation 82.1 |
| Olo 10 mcg qd | Maximum Concentration (Cmax) | Olodaterol (N=0;0;21;44;58) | 4.63 Picogram/milliliter | Geometric Coefficient of Variation 59.7 |
| Olo 10 mcg qd | Maximum Concentration (Cmax) | Olodaterol glucuronide (N=0;0;38;54;57) | 5.00 Picogram/milliliter | Geometric Coefficient of Variation 50.4 |
| Olo 20 mcg qd | Maximum Concentration (Cmax) | Olodaterol glucuronide (N=0;0;38;54;57) | 9.54 Picogram/milliliter | Geometric Coefficient of Variation 69.7 |
| Olo 20 mcg qd | Maximum Concentration (Cmax) | Olodaterol (N=0;0;21;44;58) | 8.24 Picogram/milliliter | Geometric Coefficient of Variation 68.6 |
Secondary
Peak FEV1 (0-3h) 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. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after 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 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 Week | 0.170 Liter | Standard Error 0.036 |
| Olo 2 mcg qd | Peak FEV1 (0-3h) Response After 1 Week | 0.343 Liter | Standard Error 0.034 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 1 Week | 0.355 Liter | Standard Error 0.034 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 1 Week | 0.308 Liter | Standard Error 0.034 |
| Olo 20 mcg qd | Peak FEV1 (0-3h) Response After 1 Week | 0.407 Liter | Standard Error 0.034 |
p-value: 0.000495% CI: [0.078, 0.268]Mixed Models Analysis
p-value: 0.000295% CI: [0.09, 0.281]Mixed Models Analysis
p-value: 0.004795% CI: [0.043, 0.233]Mixed Models Analysis
p-value: <0.000195% CI: [0.142, 0.332]Mixed Models Analysis
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.
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 | 0.182 Liter | Standard Error 0.041 |
| Olo 2 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.386 Liter | Standard Error 0.039 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.335 Liter | Standard Error 0.039 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.261 Liter | Standard Error 0.038 |
| Olo 20 mcg qd | Peak FEV1 (0-3h) Response After 2 Weeks | 0.403 Liter | Standard Error 0.038 |
p-value: 0.000295% CI: [0.096, 0.312]Mixed Models Analysis
p-value: 0.005795% CI: [0.045, 0.261]Mixed Models Analysis
p-value: 0.151395% CI: [-0.029, 0.186]Mixed Models Analysis
p-value: <0.000195% CI: [0.114, 0.328]Mixed Models Analysis
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.
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 | 0.198 Liter | Standard Error 0.04 |
| Olo 2 mcg qd | Peak FEV1 (0-3h) Response After 4 Weeks | 0.363 Liter | Standard Error 0.038 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response After 4 Weeks | 0.315 Liter | Standard Error 0.038 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response After 4 Weeks | 0.279 Liter | Standard Error 0.038 |
| Olo 20 mcg qd | Peak FEV1 (0-3h) Response After 4 Weeks | 0.430 Liter | Standard Error 0.038 |
p-value: 0.002295% CI: [0.06, 0.271]Mixed Models Analysis
p-value: 0.030795% CI: [0.011, 0.223]Mixed Models Analysis
p-value: 0.13295% CI: [-0.025, 0.187]Mixed Models Analysis
p-value: <0.000195% CI: [0.127, 0.337]Mixed Models Analysis
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.
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 | 0.203 Liter | Standard Error 0.036 |
| Olo 2 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.372 Liter | Standard Error 0.034 |
| Olo 5 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.378 Liter | Standard Error 0.034 |
| Olo 10 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.376 Liter | Standard Error 0.034 |
| Olo 20 mcg qd | Peak FEV1 (0-3h) Response At Day 1 | 0.499 Liter | Standard Error 0.034 |
p-value: 0.000595% CI: [0.074, 0.263]Mixed Models Analysis
p-value: 0.000395% CI: [0.08, 0.269]Mixed Models Analysis
p-value: 0.000495% CI: [0.078, 0.268]Mixed Models Analysis
p-value: <0.000195% CI: [0.202, 0.39]Mixed Models Analysis
Secondary
Peak FVC (0-3h) Response After 1 Week
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after 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 1 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 1 Week | 0.182 Liter | Standard Error 0.044 |
| Olo 2 mcg qd | Peak FVC (0-3h) Response After 1 Week | 0.281 Liter | Standard Error 0.041 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 1 Week | 0.301 Liter | Standard Error 0.042 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 1 Week | 0.259 Liter | Standard Error 0.042 |
| Olo 20 mcg qd | Peak FVC (0-3h) Response After 1 Week | 0.367 Liter | Standard Error 0.041 |
p-value: 0.095995% CI: [-0.018, 0.216]Mixed Models Analysis
p-value: 0.04795% CI: [0.002, 0.237]Mixed Models Analysis
p-value: 0.19695% CI: [-0.04, 0.195]Mixed Models Analysis
p-value: 0.00295% CI: [0.068, 0.302]Mixed Models Analysis
Secondary
Peak FVC (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 FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after 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 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 FVC (0-3h) Response After 2 Weeks | 0.184 Liter | Standard Error 0.047 |
| Olo 2 mcg qd | Peak FVC (0-3h) Response After 2 Weeks | 0.327 Liter | Standard Error 0.045 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 2 Weeks | 0.290 Liter | Standard Error 0.045 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 2 Weeks | 0.234 Liter | Standard Error 0.045 |
| Olo 20 mcg qd | Peak FVC (0-3h) Response After 2 Weeks | 0.361 Liter | Standard Error 0.045 |
p-value: 0.02795% CI: [0.016, 0.269]Mixed Models Analysis
p-value: 0.103195% CI: [-0.021, 0.233]Mixed Models Analysis
p-value: 0.437895% CI: [-0.077, 0.177]Mixed Models Analysis
p-value: 0.006495% CI: [0.05, 0.303]Mixed Models Analysis
Secondary
Peak FVC (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 FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after 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 | 0.199 Liter | Standard Error 0.051 |
| Olo 2 mcg qd | Peak FVC (0-3h) Response After 4 Weeks | 0.274 Liter | Standard Error 0.048 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response After 4 Weeks | 0.267 Liter | Standard Error 0.048 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response After 4 Weeks | 0.235 Liter | Standard Error 0.048 |
| Olo 20 mcg qd | Peak FVC (0-3h) Response After 4 Weeks | 0.439 Liter | Standard Error 0.048 |
p-value: 0.278195% CI: [-0.061, 0.21]Mixed Models Analysis
p-value: 0.328495% CI: [-0.068, 0.204]Mixed Models Analysis
p-value: 0.60295% CI: [-0.1, 0.171]Mixed Models Analysis
p-value: 0.000695% CI: [0.104, 0.375]Mixed Models Analysis
Secondary
Peak FVC (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 FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after 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 1 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 At Day 1 | 0.218 Liter | Standard Error 0.041 |
| Olo 2 mcg qd | Peak FVC (0-3h) Response At Day 1 | 0.297 Liter | Standard Error 0.039 |
| Olo 5 mcg qd | Peak FVC (0-3h) Response At Day 1 | 0.315 Liter | Standard Error 0.039 |
| Olo 10 mcg qd | Peak FVC (0-3h) Response At Day 1 | 0.315 Liter | Standard Error 0.039 |
| Olo 20 mcg qd | Peak FVC (0-3h) Response At Day 1 | 0.398 Liter | Standard Error 0.039 |
p-value: 0.158595% CI: [-0.031, 0.188]Mixed Models Analysis
p-value: 0.084895% CI: [-0.013, 0.207]Mixed Models Analysis
p-value: 0.083895% CI: [-0.013, 0.207]Mixed Models Analysis
p-value: 0.001495% CI: [0.07, 0.289]Mixed Models Analysis
Secondary
PEFR Variability After 4 Weeks
PEFR variability represents the absolute difference between the highest morning PEFR value and the highest evening PEFR value of 1 day, divided by the arithmetic mean of these 2 PEFR values and expressed as a percent, weekly means.
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 | PEFR Variability After 4 Weeks | 11.694 percentage of PEFR | Standard Error 0.78 |
| Olo 2 mcg qd | PEFR Variability After 4 Weeks | 10.575 percentage of PEFR | Standard Error 0.736 |
| Olo 5 mcg qd | PEFR Variability After 4 Weeks | 9.343 percentage of PEFR | Standard Error 0.739 |
| Olo 10 mcg qd | PEFR Variability After 4 Weeks | 8.649 percentage of PEFR | Standard Error 0.747 |
| Olo 20 mcg qd | PEFR Variability After 4 Weeks | 8.756 percentage of PEFR | Standard Error 0.733 |
p-value: 0.289895% CI: [-3.194, 0.957]Mixed Models Analysis
p-value: 0.02795% CI: [-4.432, -0.269]Mixed Models Analysis
p-value: 0.004595% CI: [-5.138, -0.952]Mixed Models Analysis
p-value: 0.005695% CI: [-5.01, -0.865]Mixed Models Analysis
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 (a metabolite of olodaterol) in plasma at steady state.
Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration
Population: All evaluable patients were included in the pharmacokinetic (PK) analysis. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of PK parameters 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;39;45;56) | 0.333 hours |
| Olo 5 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol glucuronide (N=0;0;46;46;54) | 3.00 hours |
| Olo 10 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol (N=0;0;39;45;56) | 0.333 hours |
| Olo 10 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol glucuronide (N=0;0;46;46;54) | 3.00 hours |
| Olo 20 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol (N=0;0;39;45;56) | 0.333 hours |
| Olo 20 mcg qd | Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | Olodaterol glucuronide (N=0;0;46;46;54) | 2.97 hours |
Secondary
Time From Dosing to the Maximum Concentration (Tmax)
tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.
Time frame: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration
Population: All evaluable patients were included in the pharmacokinetic (PK) analysis. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of PK parameters 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;21;44;58) | 0.183 hours |
| Olo 5 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol glucuronide (N=0;0;38;54;57) | 2.97 hours |
| Olo 10 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol (N=0;0;21;44;58) | 0.234 hours |
| Olo 10 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol glucuronide (N=0;0;38;54;57) | 2.97 hours |
| Olo 20 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol glucuronide (N=0;0;38;54;57) | 2.97 hours |
| Olo 20 mcg qd | Time From Dosing to the Maximum Concentration (Tmax) | Olodaterol (N=0;0;21;44;58) | 0.267 hours |
Secondary
Total Score in Asthma Control Questionnaire After 4 Weeks
Adequacy of asthma control was assessed using a scale of: 0=totally controlled, to 6=Severely uncontrolled.
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 | Total Score in Asthma Control Questionnaire After 4 Weeks | 1.456 units on a scale | Standard Error 0.089 |
| Olo 2 mcg qd | Total Score in Asthma Control Questionnaire After 4 Weeks | 1.314 units on a scale | Standard Error 0.086 |
| Olo 5 mcg qd | Total Score in Asthma Control Questionnaire After 4 Weeks | 1.260 units on a scale | Standard Error 0.086 |
| Olo 10 mcg qd | Total Score in Asthma Control Questionnaire After 4 Weeks | 1.129 units on a scale | Standard Error 0.084 |
| Olo 20 mcg qd | Total Score in Asthma Control Questionnaire After 4 Weeks | 1.181 units on a scale | Standard Error 0.084 |
p-value: 0.215695% CI: [-0.368, 0.083]ANCOVA
p-value: 0.086995% CI: [-0.422, 0.029]ANCOVA
p-value: 0.004495% CI: [-0.552, -0.103]ANCOVA
p-value: 0.015895% CI: [-0.499, -0.052]ANCOVA
Secondary
Trough FEV1 Response After 1 Week
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.
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 | -0.007 Liter | Standard Error 0.033 |
| Olo 2 mcg qd | Trough FEV1 Response After 1 Week | 0.060 Liter | Standard Error 0.031 |
| Olo 5 mcg qd | Trough FEV1 Response After 1 Week | 0.094 Liter | Standard Error 0.032 |
| Olo 10 mcg qd | Trough FEV1 Response After 1 Week | 0.106 Liter | Standard Error 0.031 |
| Olo 20 mcg qd | Trough FEV1 Response After 1 Week | 0.166 Liter | Standard Error 0.031 |
p-value: 0.126495% CI: [-0.019, 0.154]Mixed Models Analysis
p-value: 0.023295% CI: [0.014, 0.188]Mixed Models Analysis
p-value: 0.010695% CI: [0.027, 0.2]Mixed Models Analysis
p-value: 0.000195% CI: [0.087, 0.26]Mixed Models Analysis
Secondary
Trough FEV1 Response After 2 Weeks
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.
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 | -0.009 Liter | Standard Error 0.036 |
| Olo 2 mcg qd | Trough FEV1 Response After 2 Weeks | 0.094 Liter | Standard Error 0.034 |
| Olo 5 mcg qd | Trough FEV1 Response After 2 Weeks | 0.080 Liter | Standard Error 0.034 |
| Olo 10 mcg qd | Trough FEV1 Response After 2 Weeks | 0.034 Liter | Standard Error 0.034 |
| Olo 20 mcg qd | Trough FEV1 Response After 2 Weeks | 0.131 Liter | Standard Error 0.034 |
p-value: 0.032995% CI: [0.008, 0.198]Mixed Models Analysis
p-value: 0.066695% CI: [-0.006, 0.184]Mixed Models Analysis
p-value: 0.373895% CI: [-0.052, 0.137]Mixed Models Analysis
p-value: 0.003795% CI: [0.046, 0.234]Mixed Models Analysis
Secondary
Trough FVC Response After 1 Week
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.
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 | 0.001 Liter | Standard Error 0.036 |
| Olo 2 mcg qd | Trough FVC Response After 1 Week | 0.053 Liter | Standard Error 0.034 |
| Olo 5 mcg qd | Trough FVC Response After 1 Week | 0.044 Liter | Standard Error 0.034 |
| Olo 10 mcg qd | Trough FVC Response After 1 Week | 0.070 Liter | Standard Error 0.034 |
| Olo 20 mcg qd | Trough FVC Response After 1 Week | 0.131 Liter | Standard Error 0.034 |
p-value: 0.264695% CI: [-0.039, 0.142]Mixed Models Analysis
p-value: 0.352795% CI: [-0.048, 0.135]Mixed Models Analysis
p-value: 0.136995% CI: [-0.022, 0.16]Mixed Models Analysis
p-value: 0.005195% CI: [0.039, 0.221]Mixed Models Analysis
Secondary
Trough FVC Response After 2 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.
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 | -0.029 Liter | Standard Error 0.041 |
| Olo 2 mcg qd | Trough FVC Response After 2 Weeks | 0.098 Liter | Standard Error 0.039 |
| Olo 5 mcg qd | Trough FVC Response After 2 Weeks | 0.069 Liter | Standard Error 0.039 |
| Olo 10 mcg qd | Trough FVC Response After 2 Weeks | -0.002 Liter | Standard Error 0.038 |
| Olo 20 mcg qd | Trough FVC Response After 2 Weeks | 0.100 Liter | Standard Error 0.038 |
p-value: 0.01795% CI: [0.023, 0.232]Mixed Models Analysis
p-value: 0.064695% CI: [-0.006, 0.204]Mixed Models Analysis
p-value: 0.60295% CI: [-0.077, 0.132]Mixed Models Analysis
p-value: 0.014795% CI: [0.026, 0.233]Mixed Models Analysis
Secondary
Trough FVC Response After 4 Weeks
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.
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 | 0.018 Liter | Standard Error 0.041 |
| Olo 2 mcg qd | Trough FVC Response After 4 Weeks | 0.055 Liter | Standard Error 0.039 |
| Olo 5 mcg qd | Trough FVC Response After 4 Weeks | 0.076 Liter | Standard Error 0.039 |
| Olo 10 mcg qd | Trough FVC Response After 4 Weeks | 0.042 Liter | Standard Error 0.039 |
| Olo 20 mcg qd | Trough FVC Response After 4 Weeks | 0.166 Liter | Standard Error 0.038 |
p-value: 0.490295% CI: [-0.068, 0.142]Mixed Models Analysis
p-value: 0.283295% CI: [-0.048, 0.164]Mixed Models Analysis
p-value: 0.651695% CI: [-0.081, 0.13]Mixed Models Analysis
p-value: 0.00695% CI: [0.042, 0.252]Mixed Models Analysis
Secondary
Weekly Mean Evening PEFR After 4 Weeks
Response was defined as change from baseline. 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: 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 | Weekly Mean Evening PEFR After 4 Weeks | 384.08 Liter/minute | Standard Error 5.585 |
| Olo 2 mcg qd | Weekly Mean Evening PEFR After 4 Weeks | 407.05 Liter/minute | Standard Error 5.256 |
| Olo 5 mcg qd | Weekly Mean Evening PEFR After 4 Weeks | 408.68 Liter/minute | Standard Error 5.297 |
| Olo 10 mcg qd | Weekly Mean Evening PEFR After 4 Weeks | 420.88 Liter/minute | Standard Error 5.341 |
| Olo 20 mcg qd | Weekly Mean Evening PEFR After 4 Weeks | 426.58 Liter/minute | Standard Error 5.258 |
p-value: 0.00395% CI: [7.883, 38.057]Mixed Models Analysis
p-value: 0.001695% CI: [9.446, 39.754]Mixed Models Analysis
p-value: <0.000195% CI: [21.598, 52.015]Mixed Models Analysis
p-value: <0.000195% CI: [27.399, 57.611]Mixed Models Analysis
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 \[albuterol\]) as assessed by the e-Diary (e-Diary incorporated in AM2+).
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 | 1.449 Number of Puffs | Standard Error 0.19 |
| Olo 2 mcg qd | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 1.162 Number of Puffs | Standard Error 0.179 |
| Olo 5 mcg qd | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 0.923 Number of Puffs | Standard Error 0.181 |
| Olo 10 mcg qd | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 1.117 Number of Puffs | Standard Error 0.182 |
| Olo 20 mcg qd | Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks | 0.856 Number of Puffs | Standard Error 0.179 |
p-value: 0.264595% CI: [-0.793, 0.218]ANCOVA
p-value: 0.042395% CI: [-1.034, -0.018]ANCOVA
p-value: 0.200895% CI: [-0.842, 0.178]ANCOVA
p-value: 0.021895% CI: [-1.098, -0.087]ANCOVA
Secondary
Weekly Mean Pre-dose Morning PEFR After 4 Weeks
Response was defined as change from baseline. Baseline peak expiratory flow response (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: 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 | Weekly Mean Pre-dose Morning PEFR After 4 Weeks | 368.18 Liter/minute | Standard Error 5.713 |
| Olo 2 mcg qd | Weekly Mean Pre-dose Morning PEFR After 4 Weeks | 384.42 Liter/minute | Standard Error 5.377 |
| Olo 5 mcg qd | Weekly Mean Pre-dose Morning PEFR After 4 Weeks | 396.06 Liter/minute | Standard Error 5.419 |
| Olo 10 mcg qd | Weekly Mean Pre-dose Morning PEFR After 4 Weeks | 404.26 Liter/minute | Standard Error 5.465 |
| Olo 20 mcg qd | Weekly Mean Pre-dose Morning PEFR After 4 Weeks | 411.13 Liter/minute | Standard Error 5.377 |
p-value: 0.039395% CI: [0.801, 31.675]Mixed Models Analysis
p-value: 0.000595% CI: [12.379, 43.378]Mixed Models Analysis
p-value: <0.000195% CI: [20.512, 51.633]Mixed Models Analysis
p-value: <0.000195% CI: [27.498, 58.389]Mixed Models Analysis