Asthma
Conditions
Brief summary
This study will compare efficacy and safety of different regimens of olodaterol administration in asthma (once daily, twice daily) with placebo in a complete cross-over design each within one of the two daily dose groups (medium or high daily dose).
Interventions
Inhaled Placebo of Olodaterol twice daily
DRUGOlodaterol low daily dose twice daily
Inhaled Olodaterol medium daily dose administered as low dose twice daily
DRUGOlodaterol medium daily dose twice daily
Inhaled Olodaterol high daily dose administered as medium dose twice daily
DRUGOlodaterol high daily dose once daily and placebo
Inhaled Olodaterol high daily dose administered as one full dose once daily and placebo once daily
DRUGOlodaterol medium daily dose once daily and placebo
Inhaled Olodaterol medium daily dose administered as one full dose once daily and placebo once daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Patients of either sex. 2. Aged 18 to 70 years. 3. A current diagnosis and a documented minimum 3 month history of asthma Global Initiative for Asthma (GINA) treatment steps 3 and 4. 4. Prebronchodilator Forced Expiratory Volume in one second (FEV1) \>= 60% predicted and \< 90% predicted according to European Coal and Steel Community (ECSC). 5. Increase in FEV1 \>=12% and \>=200 mL 15 min. after 400 µg salbutamol (albuterol); 6. Stable on medium to high dose inhaled corticosteroids (ICS) or low to high dose ICS in combination with a long acting beta-adrenergics (LABA) for at least 6 weeks prior to screening. Stable on ICS mono component of the former fixed LABA/ICS treatment for at least 48 hours prior to Visit 1b.
Exclusion criteria
1. Patients with a significant disease other than asthma. 2. History of frequent seasonal exacerbations of asthma (defined as one or more seasonal exacerbations every year for the past three years). 3. Upper respiratory tract infection in the past 3 weeks prior to screening visit 1b. 4. Oral or other systemic corticosteroids in the past 6 weeks. 5. Patients with allergen desensitization therapy if started within two years, if they are not on an established maintenance regimen characterized by dose adjustments but no further increase to the tolerable maximum in the same course of immunotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. |
| Peak FEV1 Within 24 Hours Post-dose Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak FEV1 within 24 hours post dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. |
| Trough FEV1 Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. |
| Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. |
| Peak FVC Within 24 Hours Post-dose Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC within 24 hours post-dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. |
| Trough FVC Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were defined as the mean of 2 FVC values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. |
| Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds. |
| Mean Pre-dose Morning FEV1 (FEV1 a.m.) | 0-3 weeks | FEV1 a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. |
| PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds. |
| Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds. |
| FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. |
| Trough PEF Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Trough values were defined as the mean of 2 PEF values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. |
| Mean Pre-dose Morning PEF (PEF a.m.) | 0-3 weeks | PEF a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. |
| Mean Pre-dose Evening PEF (PEF p.m.) | 0-3 weeks | PEF p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. |
| PEF Daily Variability | 0-3 weeks | PEF daily variability was assessed by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). PEF daily variability is the absolute difference between the morning and the evening PEF value divided by the mean of these two values, expressed as a percent. Means are adjusted for treatment, period, patient and study baseline. |
| Mean Pre-dose Evening FEV1 (FEV1 p.m.) | 0-3 weeks | FEV1 p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. |
| Mean Number of Puffs of Rescue Medication During the Whole Day | 0-3 weeks | Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM3 device (overall mean number obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. |
| Percentage of Asthma Symptom Free Days | 0-3 weeks | Percentage of asthma-symptom free days of each treatment period was calculated as the number of symptom-free days divided by the number of days on treatment multiplied by 100. A symptom-free day was defined as a day in which no asthma symptoms were recorded, no rescue medication was recorded, activities during the day were not at all limited due to asthma, no shortness of breath during the day was recorded, no wheezing or coughing during the day and no night-time awakenings due to asthma were recorded. Assessed by patients at home using the AM3 device. |
| Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | 0-3 weeks | Assessed by patients at home using the AM3 device during each period of randomised treatment. |
| Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | 0-3 weeks | Assessed by patients at home using the AM3 device during each period of randomised treatment . |
| Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | 0-3 weeks | Assessed by patients at home using the AM3 device during each period of randomised treatment. |
| Total Asthma Control Questionnaire (ACQ) Score | 3 weeks | Control of asthma as assessed by the ACQ at the end of each 3-week treatment period.The ACQ contains 7 questions, each question has a 7 point scale from 0 (no symptoms) till 6 (highest intensity). Total score was defined as the sum of all items divided by the number of items. |
| Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | 3 weeks + 12 days | Clinical relevant abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period. |
| Peak PEF Within 24 Hours Post-dose Response | 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks | Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Peak PEF within 24 hours post dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. |
Countries
Austria, Germany, Hungary, Slovakia, Slovenia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Total This was a double-blind, 3-period crossover trial. 206 patients were assigned randomly to one of 12 treatment sequences with either 5 microgram (mcg) Olodaterol (Olo) once daily (qd) and 2.5 mcg Olodaterol twice daily (bid) and placebo (6 sequences) or 10 mcg Olodaterol qd and 5 mcg Olodaterol bid and placebo (6 sequences). The duration of each treatment period was 3 weeks separated by washout periods of 2 weeks. | 206 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Study Total |
|---|---|
| Age, Continuous | 43.7 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 109 Participants |
| Sex: Female, Male Male | 97 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 | 0 / 201 | 0 / 101 | 0 / 101 | 0 / 101 | 0 / 102 |
| serious Total, serious adverse events | 2 / 201 | 1 / 101 | 0 / 101 | 1 / 101 | 0 / 102 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: Full analysis set (FAS). FAS is defined as all patients in the treated set for whom the baseline (pre-dose) value is available, and who have a value for the primary endpoint for at least one crossover period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period | 0.022 Liter | Standard Error 0.02 |
| Olo 2.5 mcg Bid | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period | 0.213 Liter | Standard Error 0.024 |
| Olo 5 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period | 0.173 Liter | Standard Error 0.024 |
| Olo 5 mcg Bid | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period | 0.250 Liter | Standard Error 0.024 |
| Olo 10 mcg qd | Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period | 0.231 Liter | Standard Error 0.024 |
p-value: <0.000195% CI: [0.152, 0.229]Mixed Models Analysis
p-value: <0.000195% CI: [0.17, 0.247]Mixed Models Analysis
p-value: <0.000195% CI: [0.111, 0.189]Mixed Models Analysis
p-value: <0.000195% CI: [0.19, 0.266]Mixed Models Analysis
Secondary
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Clinical relevant abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.
Time frame: 3 weeks + 12 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urea abnormal | 0 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Gamma-glutamyltransferase increased | 0 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Atrioventricular block first degree | 0 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urine present | 1 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatinine increased | 0 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Anaemia | 0 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Hypertension | 0 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Aspartate aminotransferase increased | 0 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatine phosphokinase increased | 1 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood glucose increased | 0 Participants |
| Placebo | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Sinus tachycardia | 1 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood glucose increased | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Gamma-glutamyltransferase increased | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urea abnormal | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Sinus tachycardia | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Atrioventricular block first degree | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Anaemia | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Aspartate aminotransferase increased | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Hypertension | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urine present | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatinine increased | 0 Participants |
| Olo 2.5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatine phosphokinase increased | 0 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urea abnormal | 1 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Atrioventricular block first degree | 1 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Sinus tachycardia | 0 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Aspartate aminotransferase increased | 0 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatinine increased | 1 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood glucose increased | 0 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Gamma-glutamyltransferase increased | 0 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatine phosphokinase increased | 0 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urine present | 0 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Anaemia | 0 Participants |
| Olo 5 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Hypertension | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatinine increased | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Atrioventricular block first degree | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Sinus tachycardia | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Hypertension | 2 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Anaemia | 1 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Aspartate aminotransferase increased | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urea abnormal | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatine phosphokinase increased | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urine present | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood glucose increased | 0 Participants |
| Olo 5 mcg Bid | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Gamma-glutamyltransferase increased | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Atrioventricular block first degree | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Gamma-glutamyltransferase increased | 1 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatinine increased | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood creatine phosphokinase increased | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Aspartate aminotransferase increased | 1 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Hypertension | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urine present | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Sinus tachycardia | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Anaemia | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood urea abnormal | 0 Participants |
| Olo 10 mcg qd | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Blood glucose increased | 1 Participants |
Secondary
FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period | 0.052 Liter | Standard Error 0.02 |
| Olo 2.5 mcg Bid | FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period | 0.242 Liter | Standard Error 0.024 |
| Olo 5 mcg qd | FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period | 0.212 Liter | Standard Error 0.024 |
| Olo 5 mcg Bid | FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period | 0.266 Liter | Standard Error 0.024 |
| Olo 10 mcg qd | FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period | 0.272 Liter | Standard Error 0.024 |
p-value: <0.000195% CI: [0.15, 0.229]Mixed Models Analysis
p-value: <0.000195% CI: [0.121, 0.199]Mixed Models Analysis
p-value: <0.000195% CI: [0.175, 0.253]Mixed Models Analysis
p-value: <0.000195% CI: [0.181, 0.258]Mixed Models Analysis
Secondary
FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period | -0.010 Liter | Standard Error 0.02 |
| Olo 2.5 mcg Bid | FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period | 0.186 Liter | Standard Error 0.025 |
| Olo 5 mcg qd | FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period | 0.135 Liter | Standard Error 0.025 |
| Olo 5 mcg Bid | FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period | 0.233 Liter | Standard Error 0.025 |
| Olo 10 mcg qd | FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period | 0.189 Liter | Standard Error 0.025 |
p-value: <0.000195% CI: [0.153, 0.238]Mixed Models Analysis
p-value: <0.000195% CI: [0.102, 0.187]Mixed Models Analysis
p-value: <0.000195% CI: [0.2, 0.285]Mixed Models Analysis
p-value: <0.000195% CI: [0.156, 0.241]Mixed Models Analysis
Secondary
Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | -0.004 Liter | Standard Error 0.022 |
| Olo 2.5 mcg Bid | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.132 Liter | Standard Error 0.027 |
| Olo 5 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.119 Liter | Standard Error 0.027 |
| Olo 5 mcg Bid | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.138 Liter | Standard Error 0.026 |
| Olo 10 mcg qd | Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.143 Liter | Standard Error 0.026 |
p-value: <0.000195% CI: [0.091, 0.18]Mixed Models Analysis
p-value: <0.000195% CI: [0.078, 0.167]Mixed Models Analysis
p-value: <0.000195% CI: [0.098, 0.186]Mixed Models Analysis
p-value: <0.000195% CI: [0.103, 0.191]Mixed Models Analysis
Secondary
FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | -0.029 Liter | Standard Error 0.021 |
| Olo 2.5 mcg Bid | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.116 Liter | Standard Error 0.026 |
| Olo 5 mcg qd | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.099 Liter | Standard Error 0.026 |
| Olo 5 mcg Bid | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.127 Liter | Standard Error 0.026 |
| Olo 10 mcg qd | FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.111 Liter | Standard Error 0.026 |
p-value: <0.000195% CI: [0.102, 0.188]Mixed Models Analysis
p-value: <0.000195% CI: [0.085, 0.171]Mixed Models Analysis
p-value: <0.000195% CI: [0.113, 0.198]Mixed Models Analysis
p-value: <0.000195% CI: [0.098, 0.182]Mixed Models Analysis
Secondary
FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | -0.056 Liter | Standard Error 0.023 |
| Olo 2.5 mcg Bid | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.102 Liter | Standard Error 0.028 |
| Olo 5 mcg qd | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.081 Liter | Standard Error 0.028 |
| Olo 5 mcg Bid | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.114 Liter | Standard Error 0.028 |
| Olo 10 mcg qd | FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.079 Liter | Standard Error 0.028 |
p-value: <0.000195% CI: [0.11, 0.206]Mixed Models Analysis
p-value: <0.000195% CI: [0.09, 0.185]Mixed Models Analysis
p-value: <0.000195% CI: [0.123, 0.218]Mixed Models Analysis
p-value: <0.000195% CI: [0.087, 0.182]Mixed Models Analysis
Secondary
Mean Number of Puffs of Rescue Medication During the Whole Day
Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM3 device (overall mean number obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Number of Puffs of Rescue Medication During the Whole Day | 1.665 Puffs | Standard Error 0.091 |
| Olo 2.5 mcg Bid | Mean Number of Puffs of Rescue Medication During the Whole Day | 1.110 Puffs | Standard Error 0.12 |
| Olo 5 mcg qd | Mean Number of Puffs of Rescue Medication During the Whole Day | 1.028 Puffs | Standard Error 0.119 |
| Olo 5 mcg Bid | Mean Number of Puffs of Rescue Medication During the Whole Day | 1.077 Puffs | Standard Error 0.119 |
| Olo 10 mcg qd | Mean Number of Puffs of Rescue Medication During the Whole Day | 1.119 Puffs | Standard Error 0.119 |
p-value: <0.000195% CI: [-0.78, -0.329]Mixed Models Analysis
p-value: <0.000195% CI: [-0.862, -0.412]Mixed Models Analysis
p-value: <0.000195% CI: [-0.813, -0.364]Mixed Models Analysis
p-value: <0.000195% CI: [-0.77, -0.322]Mixed Models Analysis
Secondary
Mean Pre-dose Evening FEV1 (FEV1 p.m.)
FEV1 p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Pre-dose Evening FEV1 (FEV1 p.m.) | 2474.3 mL | Standard Error 17.692 |
| Olo 2.5 mcg Bid | Mean Pre-dose Evening FEV1 (FEV1 p.m.) | 2616.6 mL | Standard Error 21.949 |
| Olo 5 mcg qd | Mean Pre-dose Evening FEV1 (FEV1 p.m.) | 2606.5 mL | Standard Error 21.884 |
| Olo 5 mcg Bid | Mean Pre-dose Evening FEV1 (FEV1 p.m.) | 2616.5 mL | Standard Error 21.81 |
| Olo 10 mcg qd | Mean Pre-dose Evening FEV1 (FEV1 p.m.) | 2631.7 mL | Standard Error 21.809 |
p-value: <0.000195% CI: [104.916, 179.586]Mixed Models Analysis
p-value: <0.000195% CI: [94.954, 169.322]Mixed Models Analysis
p-value: <0.000195% CI: [105.021, 179.251]Mixed Models Analysis
p-value: <0.000195% CI: [120.192, 194.42]Mixed Models Analysis
Secondary
Mean Pre-dose Evening PEF (PEF p.m.)
PEF p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Pre-dose Evening PEF (PEF p.m.) | 409.93 Liter/min | Standard Error 2.717 |
| Olo 2.5 mcg Bid | Mean Pre-dose Evening PEF (PEF p.m.) | 438.80 Liter/min | Standard Error 3.418 |
| Olo 5 mcg qd | Mean Pre-dose Evening PEF (PEF p.m.) | 441.98 Liter/min | Standard Error 3.407 |
| Olo 5 mcg Bid | Mean Pre-dose Evening PEF (PEF p.m.) | 441.74 Liter/min | Standard Error 3.395 |
| Olo 10 mcg qd | Mean Pre-dose Evening PEF (PEF p.m.) | 443.25 Liter/min | Standard Error 3.395 |
p-value: <0.000195% CI: [22.884, 34.856]Mixed Models Analysis
p-value: <0.000195% CI: [26.094, 38.018]Mixed Models Analysis
p-value: <0.000195% CI: [25.864, 37.767]Mixed Models Analysis
p-value: <0.000195% CI: [27.375, 39.278]Mixed Models Analysis
Secondary
Mean Pre-dose Morning FEV1 (FEV1 a.m.)
FEV1 a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Pre-dose Morning FEV1 (FEV1 a.m.) | 2425.1 mL | Standard Error 17.87 |
| Olo 2.5 mcg Bid | Mean Pre-dose Morning FEV1 (FEV1 a.m.) | 2598.5 mL | Standard Error 22.276 |
| Olo 5 mcg qd | Mean Pre-dose Morning FEV1 (FEV1 a.m.) | 2580.2 mL | Standard Error 22.208 |
| Olo 5 mcg Bid | Mean Pre-dose Morning FEV1 (FEV1 a.m.) | 2574.3 mL | Standard Error 22.133 |
| Olo 10 mcg qd | Mean Pre-dose Morning FEV1 (FEV1 a.m.) | 2575.5 mL | Standard Error 22.133 |
p-value: <0.000195% CI: [135.099, 211.682]Mixed Models Analysis
p-value: <0.000195% CI: [116.961, 193.234]Mixed Models Analysis
p-value: <0.000195% CI: [111.204, 187.333]Mixed Models Analysis
p-value: <0.000195% CI: [112.377, 188.505]Mixed Models Analysis
Secondary
Mean Pre-dose Morning PEF (PEF a.m.)
PEF a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Pre-dose Morning PEF (PEF a.m.) | 395.36 Liter/min | Standard Error 2.857 |
| Olo 2.5 mcg Bid | Mean Pre-dose Morning PEF (PEF a.m.) | 428.32 Liter/min | Standard Error 3.586 |
| Olo 5 mcg qd | Mean Pre-dose Morning PEF (PEF a.m.) | 427.99 Liter/min | Standard Error 3.575 |
| Olo 5 mcg Bid | Mean Pre-dose Morning PEF (PEF a.m.) | 427.02 Liter/min | Standard Error 3.562 |
| Olo 10 mcg qd | Mean Pre-dose Morning PEF (PEF a.m.) | 424.26 Liter/min | Standard Error 3.562 |
p-value: <0.000195% CI: [26.709, 39.206]Mixed Models Analysis
p-value: <0.000195% CI: [26.409, 38.855]Mixed Models Analysis
p-value: <0.000195% CI: [25.448, 37.872]Mixed Models Analysis
p-value: <0.000195% CI: [22.683, 35.107]Mixed Models Analysis
Secondary
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
Assessed by patients at home using the AM3 device during each period of randomised treatment.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up > 5 times | 5 Number of patients |
| Placebo | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Did not wake up | 93 Number of patients |
| Placebo | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Was awake all night | 0 Number of patients |
| Placebo | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up once | 67 Number of patients |
| Placebo | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up 2-5 times | 36 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up > 5 times | 0 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up 2-5 times | 18 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up once | 31 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Was awake all night | 0 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Did not wake up | 50 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up 2-5 times | 10 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Did not wake up | 53 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up once | 36 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up > 5 times | 1 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Was awake all night | 0 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Was awake all night | 2 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Did not wake up | 44 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up > 5 times | 0 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up 2-5 times | 14 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up once | 41 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up 2-5 times | 19 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up > 5 times | 2 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Did not wake up | 47 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Was awake all night | 1 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) | Woke up once | 32 Number of patients |
Secondary
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
Assessed by patients at home using the AM3 device during each period of randomised treatment .
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Severe asthma symptoms | 18 Number of patients |
| Placebo | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | No asthma symptoms | 31 Number of patients |
| Placebo | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Very severe asthma symptoms | 1 Number of patients |
| Placebo | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Mild asthma symptoms | 66 Number of patients |
| Placebo | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Moderate asthma symptoms | 85 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Severe asthma symptoms | 4 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Moderate asthma symptoms | 25 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Mild asthma symptoms | 45 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Very severe asthma symptoms | 1 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | No asthma symptoms | 24 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Moderate asthma symptoms | 27 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | No asthma symptoms | 27 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Mild asthma symptoms | 42 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Severe asthma symptoms | 3 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Very severe asthma symptoms | 1 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Very severe asthma symptoms | 1 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | No asthma symptoms | 18 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Severe asthma symptoms | 4 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Moderate asthma symptoms | 36 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Mild asthma symptoms | 42 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Moderate asthma symptoms | 37 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Severe asthma symptoms | 2 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | No asthma symptoms | 20 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Very severe asthma symptoms | 1 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) | Mild asthma symptoms | 41 Number of patients |
Secondary
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
Assessed by patients at home using the AM3 device during each period of randomised treatment.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Severe asthma symptoms | 9 Number of patients |
| Placebo | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | No asthma symptoms | 39 Number of patients |
| Placebo | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Very severe asthma symptoms | 3 Number of patients |
| Placebo | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Mild asthma symptoms | 76 Number of patients |
| Placebo | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Moderate asthma symptoms | 74 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Severe asthma symptoms | 4 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Moderate asthma symptoms | 26 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Mild asthma symptoms | 35 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Very severe asthma symptoms | 2 Number of patients |
| Olo 2.5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | No asthma symptoms | 32 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Moderate asthma symptoms | 32 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | No asthma symptoms | 29 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Mild asthma symptoms | 38 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Severe asthma symptoms | 1 Number of patients |
| Olo 5 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Very severe asthma symptoms | 0 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Very severe asthma symptoms | 1 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | No asthma symptoms | 21 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Severe asthma symptoms | 2 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Moderate asthma symptoms | 29 Number of patients |
| Olo 5 mcg Bid | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Mild asthma symptoms | 48 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Moderate asthma symptoms | 35 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Severe asthma symptoms | 3 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | No asthma symptoms | 21 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Very severe asthma symptoms | 2 Number of patients |
| Olo 10 mcg qd | Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) | Mild asthma symptoms | 40 Number of patients |
Secondary
Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.101 Liter/sec | Standard Error 0.06 |
| Olo 2.5 mcg Bid | Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.730 Liter/sec | Standard Error 0.075 |
| Olo 5 mcg qd | Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.703 Liter/sec | Standard Error 0.075 |
| Olo 5 mcg Bid | Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.732 Liter/sec | Standard Error 0.074 |
| Olo 10 mcg qd | Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response | 0.787 Liter/sec | Standard Error 0.074 |
p-value: <0.000195% CI: [0.5, 0.757]Mixed Models Analysis
p-value: <0.000195% CI: [0.473, 0.73]Mixed Models Analysis
p-value: <0.000195% CI: [0.503, 0.758]Mixed Models Analysis
p-value: <0.000195% CI: [0.558, 0.813]Mixed Models Analysis
Secondary
Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response | -0.014 Liter/sec | Standard Error 0.059 |
| Olo 2.5 mcg Bid | Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.627 Liter/sec | Standard Error 0.073 |
| Olo 5 mcg qd | Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.563 Liter/sec | Standard Error 0.073 |
| Olo 5 mcg Bid | Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.653 Liter/sec | Standard Error 0.073 |
| Olo 10 mcg qd | Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response | 0.629 Liter/sec | Standard Error 0.073 |
p-value: <0.000195% CI: [0.516, 0.765]Mixed Models Analysis
p-value: <0.000195% CI: [0.453, 0.701]Mixed Models Analysis
p-value: <0.000195% CI: [0.544, 0.79]Mixed Models Analysis
p-value: <0.000195% CI: [0.519, 0.766]Mixed Models Analysis
Secondary
Peak FEV1 Within 24 Hours Post-dose Response
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak FEV1 within 24 hours post dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FEV1 Within 24 Hours Post-dose Response | 0.227 Liter | Standard Error 0.021 |
| Olo 2.5 mcg Bid | Peak FEV1 Within 24 Hours Post-dose Response | 0.410 Liter | Standard Error 0.027 |
| Olo 5 mcg qd | Peak FEV1 Within 24 Hours Post-dose Response | 0.380 Liter | Standard Error 0.027 |
| Olo 5 mcg Bid | Peak FEV1 Within 24 Hours Post-dose Response | 0.449 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Peak FEV1 Within 24 Hours Post-dose Response | 0.437 Liter | Standard Error 0.026 |
p-value: <0.000195% CI: [0.138, 0.228]Mixed Models Analysis
p-value: <0.000195% CI: [0.108, 0.198]Mixed Models Analysis
p-value: <0.000195% CI: [0.177, 0.267]Mixed Models Analysis
p-value: <0.000195% CI: [0.165, 0.255]Mixed Models Analysis
Secondary
Peak FVC Within 24 Hours Post-dose Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC within 24 hours post-dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak FVC Within 24 Hours Post-dose Response | 0.246 Liter | Standard Error 0.024 |
| Olo 2.5 mcg Bid | Peak FVC Within 24 Hours Post-dose Response | 0.382 Liter | Standard Error 0.03 |
| Olo 5 mcg qd | Peak FVC Within 24 Hours Post-dose Response | 0.371 Liter | Standard Error 0.03 |
| Olo 5 mcg Bid | Peak FVC Within 24 Hours Post-dose Response | 0.390 Liter | Standard Error 0.03 |
| Olo 10 mcg qd | Peak FVC Within 24 Hours Post-dose Response | 0.373 Liter | Standard Error 0.029 |
p-value: <0.000195% CI: [0.084, 0.187]Mixed Models Analysis
p-value: <0.000195% CI: [0.073, 0.176]Mixed Models Analysis
p-value: <0.000195% CI: [0.093, 0.195]Mixed Models Analysis
p-value: <0.000195% CI: [0.075, 0.177]Mixed Models Analysis
Secondary
Peak PEF Within 24 Hours Post-dose Response
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Peak PEF within 24 hours post dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak PEF Within 24 Hours Post-dose Response | 0.663 Liter/sec | Standard Error 0.068 |
| Olo 2.5 mcg Bid | Peak PEF Within 24 Hours Post-dose Response | 1.254 Liter/sec | Standard Error 0.087 |
| Olo 5 mcg qd | Peak PEF Within 24 Hours Post-dose Response | 1.185 Liter/sec | Standard Error 0.087 |
| Olo 5 mcg Bid | Peak PEF Within 24 Hours Post-dose Response | 1.257 Liter/sec | Standard Error 0.086 |
| Olo 10 mcg qd | Peak PEF Within 24 Hours Post-dose Response | 1.286 Liter/sec | Standard Error 0.086 |
p-value: <0.000195% CI: [0.436, 0.746]Mixed Models Analysis
p-value: <0.000195% CI: [0.366, 0.677]Mixed Models Analysis
p-value: <0.000195% CI: [0.439, 0.749]Mixed Models Analysis
p-value: <0.000195% CI: [0.468, 0.777]Mixed Models Analysis
Secondary
PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response | -0.135 Liter/sec | Standard Error 0.061 |
| Olo 2.5 mcg Bid | PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.530 Liter/sec | Standard Error 0.077 |
| Olo 5 mcg qd | PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.430 Liter/sec | Standard Error 0.076 |
| Olo 5 mcg Bid | PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.567 Liter/sec | Standard Error 0.076 |
| Olo 10 mcg qd | PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response | 0.464 Liter/sec | Standard Error 0.076 |
p-value: <0.000195% CI: [0.532, 0.799]Mixed Models Analysis
p-value: <0.000195% CI: [0.431, 0.698]Mixed Models Analysis
p-value: <0.000195% CI: [0.569, 0.835]Mixed Models Analysis
p-value: <0.000195% CI: [0.467, 0.732]Mixed Models Analysis
Secondary
PEF Daily Variability
PEF daily variability was assessed by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). PEF daily variability is the absolute difference between the morning and the evening PEF value divided by the mean of these two values, expressed as a percent. Means are adjusted for treatment, period, patient and study baseline.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PEF Daily Variability | 10.157 Percentage | Standard Error 0.288 |
| Olo 2.5 mcg Bid | PEF Daily Variability | 8.576 Percentage | Standard Error 0.371 |
| Olo 5 mcg qd | PEF Daily Variability | 8.732 Percentage | Standard Error 0.369 |
| Olo 5 mcg Bid | PEF Daily Variability | 8.419 Percentage | Standard Error 0.368 |
| Olo 10 mcg qd | PEF Daily Variability | 9.468 Percentage | Standard Error 0.368 |
p-value: <0.000195% CI: [-2.262, -0.9]Mixed Models Analysis
p-value: <0.000195% CI: [-2.104, -0.748]Mixed Models Analysis
p-value: <0.000195% CI: [-2.415, -1.062]Mixed Models Analysis
p-value: 0.045895% CI: [-1.366, -0.013]Mixed Models Analysis
Secondary
Percentage of Asthma Symptom Free Days
Percentage of asthma-symptom free days of each treatment period was calculated as the number of symptom-free days divided by the number of days on treatment multiplied by 100. A symptom-free day was defined as a day in which no asthma symptoms were recorded, no rescue medication was recorded, activities during the day were not at all limited due to asthma, no shortness of breath during the day was recorded, no wheezing or coughing during the day and no night-time awakenings due to asthma were recorded. Assessed by patients at home using the AM3 device.
Time frame: 0-3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Asthma Symptom Free Days | 23.630 Percentage of asthma symptom free days | Standard Error 2.235 |
| Olo 2.5 mcg Bid | Percentage of Asthma Symptom Free Days | 33.929 Percentage of asthma symptom free days | Standard Error 3.554 |
| Olo 5 mcg qd | Percentage of Asthma Symptom Free Days | 36.306 Percentage of asthma symptom free days | Standard Error 3.644 |
| Olo 5 mcg Bid | Percentage of Asthma Symptom Free Days | 28.844 Percentage of asthma symptom free days | Standard Error 3.271 |
| Olo 10 mcg qd | Percentage of Asthma Symptom Free Days | 28.049 Percentage of asthma symptom free days | Standard Error 3.368 |
Secondary
Total Asthma Control Questionnaire (ACQ) Score
Control of asthma as assessed by the ACQ at the end of each 3-week treatment period.The ACQ contains 7 questions, each question has a 7 point scale from 0 (no symptoms) till 6 (highest intensity). Total score was defined as the sum of all items divided by the number of items.
Time frame: 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Asthma Control Questionnaire (ACQ) Score | 1.613 Units on a scale | Standard Error 0.04 |
| Olo 2.5 mcg Bid | Total Asthma Control Questionnaire (ACQ) Score | 1.256 Units on a scale | Standard Error 0.053 |
| Olo 5 mcg qd | Total Asthma Control Questionnaire (ACQ) Score | 1.317 Units on a scale | Standard Error 0.053 |
| Olo 5 mcg Bid | Total Asthma Control Questionnaire (ACQ) Score | 1.312 Units on a scale | Standard Error 0.053 |
| Olo 10 mcg qd | Total Asthma Control Questionnaire (ACQ) Score | 1.311 Units on a scale | Standard Error 0.053 |
p-value: <0.000195% CI: [-0.461, -0.253]Mixed Models Analysis
p-value: <0.000195% CI: [-0.4, -0.192]Mixed Models Analysis
p-value: <0.000195% CI: [-0.405, -0.198]Mixed Models Analysis
p-value: <0.000195% CI: [-0.405, -0.198]Mixed Models Analysis
Secondary
Trough FEV1 Response
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FEV1 Response | 0.033 Liter | Standard Error 0.022 |
| Olo 2.5 mcg Bid | Trough FEV1 Response | 0.189 Liter | Standard Error 0.027 |
| Olo 5 mcg qd | Trough FEV1 Response | 0.134 Liter | Standard Error 0.027 |
| Olo 5 mcg Bid | Trough FEV1 Response | 0.229 Liter | Standard Error 0.027 |
| Olo 10 mcg qd | Trough FEV1 Response | 0.205 Liter | Standard Error 0.027 |
p-value: <0.000195% CI: [0.109, 0.203]Mixed Models Analysis
p-value: <0.000195% CI: [0.054, 0.148]Mixed Models Analysis
p-value: <0.000195% CI: [0.149, 0.243]Mixed Models Analysis
p-value: <0.000195% CI: [0.125, 0.219]Mixed Models Analysis
Secondary
Trough FVC Response
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were defined as the mean of 2 FVC values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough FVC Response | -0.013 Liter | Standard Error 0.024 |
| Olo 2.5 mcg Bid | Trough FVC Response | 0.096 Liter | Standard Error 0.031 |
| Olo 5 mcg qd | Trough FVC Response | 0.079 Liter | Standard Error 0.031 |
| Olo 5 mcg Bid | Trough FVC Response | 0.105 Liter | Standard Error 0.031 |
| Olo 10 mcg qd | Trough FVC Response | 0.098 Liter | Standard Error 0.031 |
p-value: 0.000195% CI: [0.055, 0.165]Mixed Models Analysis
p-value: 0.00195% CI: [0.037, 0.147]Mixed Models Analysis
p-value: <0.000195% CI: [0.063, 0.172]Mixed Models Analysis
p-value: <0.000195% CI: [0.057, 0.166]Mixed Models Analysis
Secondary
Trough PEF Response
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Trough values were defined as the mean of 2 PEF values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Time frame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough PEF Response | -0.009 Liter/sec | Standard Error 0.062 |
| Olo 2.5 mcg Bid | Trough PEF Response | 0.520 Liter/sec | Standard Error 0.078 |
| Olo 5 mcg qd | Trough PEF Response | 0.401 Liter/sec | Standard Error 0.078 |
| Olo 5 mcg Bid | Trough PEF Response | 0.594 Liter/sec | Standard Error 0.077 |
| Olo 10 mcg qd | Trough PEF Response | 0.472 Liter/sec | Standard Error 0.077 |
p-value: <0.000195% CI: [0.396, 0.662]Mixed Models Analysis
p-value: <0.000195% CI: [0.277, 0.543]Mixed Models Analysis
p-value: <0.000195% CI: [0.471, 0.736]Mixed Models Analysis
p-value: <0.000195% CI: [0.349, 0.613]Mixed Models Analysis