Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL administered with 5 microgram tiotropium bromide solution for inhalation, delivered by the Respimat® inhaler, once daily for four weeks in patients with chronic obstructive pulmonary disease (COPD).
Interventions
DRUGBI 1744 CL plus tiotropium bromide
BI 1744 CL plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
DEVICERespimat® Inhaler
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions 2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 \>= 30% of predicted normal and \<80% of predicted normal and a post-bronchodilator FEV1 / FVC \<70% at Visit 1 3. Male or female patients, 40 years of age or older 4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years 5. 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 6. Patients must be able to inhale medication in a competent manner from the Respimat inhaler and from a metered dose inhaler (MDI). 7. additional inclusion criteria apply.
Exclusion criteria
1. Patients with a significant disease other than COPD 2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; 3. Patients with a history of asthma or a total blood eosinophil count \>= 600/mm3. 4. 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 QTcF\* 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) 5. 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, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years, a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, a history of significant alcohol or drug abuse 6. Patients who have undergone thoracotomy with pulmonary resection 7. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits. 8. Pregnant or nursing women 9. Women of childbearing potential not using two effective method of birth control (one barrier and one non-barrier). 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 two years 10. Patients who have previously been randomized in this study or are currently participating in another study 11. Patients who are unable to comply with pulmonary medication restrictions prior to randomization 12. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit 13. additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment. | 1 hour (h), 10 minutes (min) before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29 | Trough FEV1 was defined as the mean of the 2 FEV1 values at the end of the dosing interval, 24 hours post-drug administration. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Individual FEV1 Measurements | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29 | Individual FEV1 measurements \[L\] at each time point on Day 29. The presented means are adjusted. |
| FEV1 AUC 0-3h, Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29 | FEV1 Area Under the Curve (AUC) 0-3h, response \[L\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| FEV1 Peak 0-3h Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29 | FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response \[L\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| FEV1, AUC (0-6h) Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29 | FEV1, AUC (0-6h) response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| FEV1 (Unsupervised) AUC (6-12h) Response | 6 hours (h), 9h and 12h after drug administration on day 29 | FEV1 (unsupervised) AUC (6-12h) response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| Trough FVC Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15, in addition 4h, 5h, 6h after drug administration on day 29 | Trough Forced Vital Capacity (FVC) response \[L\] on days 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| Individual FVC Measurements | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29 | Individual FVC measurements \[L\] at each time point The categories correspond to the planned times for FVC measurements on Day 29. The presented means are adjusted. |
| FVC AUC (0-3h) Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29 | FVC AUC (0-3h) response \[L\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| FVC AUC (0-6h) Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29 | FVC AUC (0-6h) response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| Weekly Mean Morning PEFR | Weeks 1,2,3 and 4 | Weekly mean morning PEFR \[L/min\] on weeks 1,2,3 and 4. The presented means are adjusted. |
| FVC Peak 0-3h Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 29 | FVC peak 0-3h response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| PEFR AUC (0-3h) Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29 | Peak Expiratory Flow Rate (PEFR) AUC (0-3h) response \[L/min\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| PEFR Peak 0-3h Response | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29 | PEFR peak 0-3h response \[L/min\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| Trough FEV1 Response [L] After 2 Weeks of Treatment | 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15 | Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
| Weekly Mean Evening PEFR | Weeks 1,2,3 and 4 | Weekly mean evening PEFR \[L/min\] on weeks 1,2,3 and 4. The presented means are adjusted. |
| Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Weeks 1,2,3 and 4 | Weekly mean number of occasions of rescue therapy used per day (as occasion require (PRN) salbutamol \[albuterol\]) on weeks 1,2,3 and 4. The means presented are the adjusted mean of weekly mean. |
| Patient Global Rating | 4 weeks | Patient global rating scores treatment comparison after 4 weeks The score was evaluated on a 7-point scale : * 1 : very much better * 2 : much better * 3 : a little better * 4 : no change * 5 : a little worse * 6 : much worse * 7 : very much worse The presented means are adjusted. |
| Physician's Global Evaluation | Days 15 and 29 | Physician's global evaluation score on days 15 and 29 The score was evaluated on a 8-points scale : * Poor : 1,2 * Fair : 3,4 * Good : 5,6 * Excellent : 7,8 The presented means are adjusted |
| Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination | 14 weeks | Clinically significant abnormalities for blood chemistry, haematology, urinalysis and physical examination |
| Overall Marked Changes From Baseline in Vital Signs | Baseline to week 14 | Overall marked changes from baseline in systolic blood pressure, diastolic blood pressure and pulse rate. |
| 12-lead ECG Heart Rate | Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29 | 12-lead Electrocardiogram (ECG) Heart rate baseline and change from baseline values at other time points in Beats Per Minute (BPM) Statistics for each planned time from baseline to day 29. |
| 12-lead ECG PR Intervals | Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29 | 12-lead ECG PR intervals baseline and change from baseline at other timepoints in milliseconds. Statistics for each planned time from baseline to day 29. |
| 12-lead ECG QRS Intervals | Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29 | 12-lead ECG QRS intervals baseline and change from baseline at other time points in milliseconds Statistics for each planned time from baseline to day 29. |
| 12-lead ECG QTcF Intervals | Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29 | 12-lead ECG corrected heart rate (QT) interval, using Fridericia method (QTcF), baseline and change from baseline at other time points in milliseconds. Statistics for each planned time from baseline to day 29. |
| 12-lead ECG QTcB Intervals | Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29 | 12-lead ECG heart rate corrected QT interval, using Bazett method (QTcB), baseline and change from baseline at other time points in milliseconds. Statistics for each planned time from baseline to day 29. |
| 12-lead ECG QT Intervals | Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29 | 12-lead ECG QT intervals baseline and change from baseline at other time points in milliseconds. Statistics for each planned time from baseline to day 29. |
| AUC (0-6H) FEV1 (Unsupervised), AUC (0-6H) PEFR (Unsupervised), FVC Peak (0-3h), AUC (6-12h) FEV1 (Unsupervised), AUC (6-12h) PEFR (Unsupervised), Individual PEFR Measurements (Supervised and Unsupervised), Individual PEFR Measurements (Unsupervised) | 4 weeks | * AUC (0-6h) for FEV1, and PEFR (unsupervised) after first dose and after 2 and 4 weeks of treatment were not analysed in the study report because the pertinent information from the unsupervised Pulmonary Function Tests (PFTs) was for the time interval from 6 to 12 hours post-dosing. * FVC peak 0-3h response after the first dose and at Week 2 (supervised) and AUC (6-12h) for FEV1 and PEFR after the first dose and at Week 2 (unsupervised) were not analysed in the study report. * Individual PEFR (supervised) measurements and individual FEV1 and PEFR (unsupervised) measurements at each time point were not analysed in the study report. |
| PEFR AUC (6-12h) Response | 1 hour (h) and 10 minutes before drug administration on day 1 and 6h, 9h and 12h after drug administration on day 29 | PEFR AUC (6-12h) response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed). |
Countries
Belgium, Canada, Germany, United States
Participant flow
Pre-assignment details
This was a randomised, 2-way cross-over trial. 141 patients were randomized to one of 2 treatments sequences and treated. It was a double-blind trial in which each treatment period lasted 4 weeks. During the 2 week pre-treatment run-in and during the 2 week washout between treatment periods, patients received open-label tiotropium 5µg.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study A randomised, double-blind, 2-way cross-over study. The two treatment periods were separated by a wash-out period of 14 days during which they received open-label Tiotropium 5 mcg. The 2 treatments, administered once daily in the morning via the respimat inhaler, were :
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg | 141 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 (4 Weeks) | Adverse Event | 2 | 0 |
| Treatment Period 1 (4 Weeks) | Protocol Violation | 1 | 2 |
| Treatment Period 2 (4 Weeks) | Adverse Event | 2 | 3 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 63.67 years STANDARD_DEVIATION 8.19 |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 139 | 16 / 138 |
| serious Total, serious adverse events | 3 / 139 | 5 / 138 |
Outcome results
Primary
Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment.
Trough FEV1 was defined as the mean of the 2 FEV1 values at the end of the dosing interval, 24 hours post-drug administration. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1 hour (h), 10 minutes (min) before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
Population: Full analysis Set (FAS) which included all randomized patients who received at least one dose of study medication and had baseline data and Washout Period for at least 1 efficacy endpoint for each treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment. | 0.057 Litres | Standard Error 0.013 |
| Olo 5 µg + Tio5 µg | Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment. | 0.055 Litres | Standard Error 0.013 |
Comparison: Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.893795% CI: [-0.035, 0.031]ANCOVA
Secondary
12-lead ECG Heart Rate
12-lead Electrocardiogram (ECG) Heart rate baseline and change from baseline values at other time points in Beats Per Minute (BPM) Statistics for each planned time from baseline to day 29.
Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29
Population: TS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | 12-lead ECG Heart Rate | Baseline | 72.96 BPM | Standard Deviation 12.86 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG Heart Rate | Day1 1:00 | -2.09 BPM | Standard Deviation 7.6 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG Heart Rate | Day15 -0:30 (N=137, 137) | 0.42 BPM | Standard Deviation 11.09 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG Heart Rate | Day15 0:10 (N=135, 136) | -1.61 BPM | Standard Deviation 8.77 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG Heart Rate | Day29 -0:30 (N=134, 136) | -0.69 BPM | Standard Deviation 8.71 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG Heart Rate | Day29 1:00 (N=132, 135) | -2.34 BPM | Standard Deviation 9.75 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG Heart Rate | Day1 0:10 | -1.44 BPM | Standard Deviation 6.04 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG Heart Rate | Day29 0:10 (N=132, 135) | -2.14 BPM | Standard Deviation 9.25 |
| Olo 5 µg + Tio5 µg | 12-lead ECG Heart Rate | Day1 0:10 | -1.01 BPM | Standard Deviation 5.63 |
| Olo 5 µg + Tio5 µg | 12-lead ECG Heart Rate | Baseline | 72.38 BPM | Standard Deviation 11.96 |
| Olo 5 µg + Tio5 µg | 12-lead ECG Heart Rate | Day29 0:10 (N=132, 135) | -0.24 BPM | Standard Deviation 9.5 |
| Olo 5 µg + Tio5 µg | 12-lead ECG Heart Rate | Day1 1:00 | -1.6 BPM | Standard Deviation 7.45 |
| Olo 5 µg + Tio5 µg | 12-lead ECG Heart Rate | Day29 -0:30 (N=134, 136) | 1.68 BPM | Standard Deviation 9.43 |
| Olo 5 µg + Tio5 µg | 12-lead ECG Heart Rate | Day15 -0:30 (N=137, 137) | 1.1 BPM | Standard Deviation 8.88 |
| Olo 5 µg + Tio5 µg | 12-lead ECG Heart Rate | Day29 1:00 (N=132, 135) | -0.73 BPM | Standard Deviation 8.98 |
| Olo 5 µg + Tio5 µg | 12-lead ECG Heart Rate | Day15 0:10 (N=135, 136) | -0.79 BPM | Standard Deviation 8.97 |
Secondary
12-lead ECG PR Intervals
12-lead ECG PR intervals baseline and change from baseline at other timepoints in milliseconds. Statistics for each planned time from baseline to day 29.
Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29
Population: TS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | 12-lead ECG PR Intervals | Day29 1:00 (N=132, 135) | 1.98 mS | Standard Deviation 17.91 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG PR Intervals | Day1 1:00 (N=139, 137) | 2.12 mS | Standard Deviation 13.94 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG PR Intervals | Baseline | 160.03 mS | Standard Deviation 24.94 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG PR Intervals | Day15 -0:30 (N=136, 137) | 0.55 mS | Standard Deviation 12.56 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG PR Intervals | Day29 0:10 (N=132, 135) | -0.29 mS | Standard Deviation 13.9 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG PR Intervals | Day15 0:10 (N=135, 136) | 0.28 mS | Standard Deviation 12.17 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG PR Intervals | Day1 0:10 | -1.02 mS | Standard Deviation 12.05 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG PR Intervals | Day29 -0:30 (N=134, 135) | -1.29 mS | Standard Deviation 13.45 |
| Olo 5 µg + Tio5 µg | 12-lead ECG PR Intervals | Day29 1:00 (N=132, 135) | 0.22 mS | Standard Deviation 13.05 |
| Olo 5 µg + Tio5 µg | 12-lead ECG PR Intervals | Day29 -0:30 (N=134, 135) | -0.19 mS | Standard Deviation 15.35 |
| Olo 5 µg + Tio5 µg | 12-lead ECG PR Intervals | Day29 0:10 (N=132, 135) | -2.05 mS | Standard Deviation 16.39 |
| Olo 5 µg + Tio5 µg | 12-lead ECG PR Intervals | Baseline | 160.69 mS | Standard Deviation 29.28 |
| Olo 5 µg + Tio5 µg | 12-lead ECG PR Intervals | Day1 0:10 | -1.86 mS | Standard Deviation 17.53 |
| Olo 5 µg + Tio5 µg | 12-lead ECG PR Intervals | Day1 1:00 (N=139, 137) | 0.09 mS | Standard Deviation 11.07 |
| Olo 5 µg + Tio5 µg | 12-lead ECG PR Intervals | Day15 -0:30 (N=136, 137) | -0.95 mS | Standard Deviation 20.17 |
| Olo 5 µg + Tio5 µg | 12-lead ECG PR Intervals | Day15 0:10 (N=135, 136) | -1.24 mS | Standard Deviation 15.08 |
Secondary
12-lead ECG QRS Intervals
12-lead ECG QRS intervals baseline and change from baseline at other time points in milliseconds Statistics for each planned time from baseline to day 29.
Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29
Population: TS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | 12-lead ECG QRS Intervals | Day15 -0:30 (N=137, 137) | -0.55 mS | Standard Deviation 7.48 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QRS Intervals | Day29 1:00 (N=132, 135) | -0.33 mS | Standard Deviation 7.5 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QRS Intervals | Day29 -0:30 (N=134, 136) | -0.44 mS | Standard Deviation 7.55 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QRS Intervals | Baseline | 92.71 mS | Standard Deviation 11.92 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QRS Intervals | Day15 0:10 (N=135, 136) | -0.67 mS | Standard Deviation 6.73 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QRS Intervals | Day1 0:10 | -0.28 mS | Standard Deviation 6.29 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QRS Intervals | Day29 0:10 (N=132, 135) | -1.27 mS | Standard Deviation 6.63 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QRS Intervals | Day1 1:00 | -0.47 mS | Standard Deviation 6.39 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QRS Intervals | Day29 0:10 (N=132, 135) | -0.82 mS | Standard Deviation 7.16 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QRS Intervals | Day15 -0:30 (N=137, 137) | -0.44 mS | Standard Deviation 7.73 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QRS Intervals | Day15 0:10 (N=135, 136) | -0.32 mS | Standard Deviation 7.9 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QRS Intervals | Day29 -0:30 (N=134, 136) | -0.75 mS | Standard Deviation 7.4 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QRS Intervals | Day1 1:00 | 0.31 mS | Standard Deviation 6.34 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QRS Intervals | Day29 1:00 (N=132, 135) | -0.39 mS | Standard Deviation 7.9 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QRS Intervals | Baseline | 92.41 mS | Standard Deviation 12.14 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QRS Intervals | Day1 0:10 | -0.65 mS | Standard Deviation 6.63 |
Secondary
12-lead ECG QTcB Intervals
12-lead ECG heart rate corrected QT interval, using Bazett method (QTcB), baseline and change from baseline at other time points in milliseconds. Statistics for each planned time from baseline to day 29.
Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29
Population: TS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcB Intervals | Baseline | 418.12 mS | Standard Deviation 24.67 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcB Intervals | Day1 0:10 | -2.18 mS | Standard Deviation 16.32 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcB Intervals | Day1 1:00 (N=138, 138) | -2.57 mS | Standard Deviation 15.95 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcB Intervals | Day15 -0:30 (N=137, 137) | 0.93 mS | Standard Deviation 18.23 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcB Intervals | Day15 0:10 (N=135, 136) | -2.51 mS | Standard Deviation 20.37 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcB Intervals | Day29 -0:30 (N=134, 136) | -1.87 mS | Standard Deviation 20.43 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcB Intervals | Day29 0:10 (N=132, 135) | -3.13 mS | Standard Deviation 19.45 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcB Intervals | Day29 1:00 (N=132, 135) | -2.55 mS | Standard Deviation 23.88 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcB Intervals | Day29 1:00 (N=132, 135) | -1.69 mS | Standard Deviation 19.75 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcB Intervals | Baseline | 415.56 mS | Standard Deviation 23.35 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcB Intervals | Day15 0:10 (N=135, 136) | -1.76 mS | Standard Deviation 20.51 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcB Intervals | Day1 0:10 | 0.05 mS | Standard Deviation 16.14 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcB Intervals | Day29 0:10 (N=132, 135) | -2.33 mS | Standard Deviation 20.35 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcB Intervals | Day1 1:00 (N=138, 138) | -2.2 mS | Standard Deviation 18.05 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcB Intervals | Day29 -0:30 (N=134, 136) | 1.43 mS | Standard Deviation 21.52 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcB Intervals | Day15 -0:30 (N=137, 137) | 0.91 mS | Standard Deviation 19.72 |
Secondary
12-lead ECG QTcF Intervals
12-lead ECG corrected heart rate (QT) interval, using Fridericia method (QTcF), baseline and change from baseline at other time points in milliseconds. Statistics for each planned time from baseline to day 29.
Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29
Population: TS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcF Intervals | Baseline | 405.63 mS | Standard Deviation 21.42 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcF Intervals | Day1 0:10 | -0.89 mS | Standard Deviation 12.85 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcF Intervals | Day1 1:00 (N=138, 138) | -0.69 mS | Standard Deviation 12.79 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcF Intervals | Day15 -0:30 (N=137, 137) | 0.55 mS | Standard Deviation 14.28 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcF Intervals | Day15 0:10 (N=135, 136) | -1.16 mS | Standard Deviation 16.67 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcF Intervals | Day29 -0:30 (N=134, 136) | -1.35 mS | Standard Deviation 17.18 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcF Intervals | Day29 0:10 (N=132, 135) | -1.22 mS | Standard Deviation 15.05 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QTcF Intervals | Day29 1:00 (N=132, 135) | -0.56 mS | Standard Deviation 18.24 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcF Intervals | Day29 1:00 (N=132, 135) | -1.05 mS | Standard Deviation 16.49 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcF Intervals | Baseline | 403.53 mS | Standard Deviation 20.49 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcF Intervals | Day15 0:10 (N=135, 136) | -1.02 mS | Standard Deviation 17.37 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcF Intervals | Day1 0:10 | 0.97 mS | Standard Deviation 13.49 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcF Intervals | Day29 0:10 (N=132, 135) | -2.08 mS | Standard Deviation 16.56 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcF Intervals | Day1 1:00 (N=138, 138) | -0.61 mS | Standard Deviation 15.19 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcF Intervals | Day29 -0:30 (N=134, 136) | -0.24 mS | Standard Deviation 17.39 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QTcF Intervals | Day15 -0:30 (N=137, 137) | -0.03 mS | Standard Deviation 16.5 |
Secondary
12-lead ECG QT Intervals
12-lead ECG QT intervals baseline and change from baseline at other time points in milliseconds. Statistics for each planned time from baseline to day 29.
Time frame: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29
Population: TS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | 12-lead ECG QT Intervals | Baseline | 382.73 mS | Standard Deviation 31.87 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QT Intervals | Day1 1:00 (N=138, 138) | 2.97 mS | Standard Deviation 15.89 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QT Intervals | Day15 0:10 (N=135, 136) | 1.44 mS | Standard Deviation 20.59 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QT Intervals | Day29 -0:30 (N=134, 136) | -0.59 mS | Standard Deviation 20.91 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QT Intervals | Day1 0:10 | 1.59 mS | Standard Deviation 13.09 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QT Intervals | Day29 0:10 (N=132, 135) | 2.27 mS | Standard Deviation 19.24 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QT Intervals | Day29 1:00 (N=132, 135) | 3.14 mS | Standard Deviation 19.28 |
| Olo 2 µg + Tio 5 µg | 12-lead ECG QT Intervals | Day15 -0:30 (N=137, 137) | -0.09 mS | Standard Deviation 19.95 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QT Intervals | Day29 1:00 (N=132, 135) | 0.2 mS | Standard Deviation 20.51 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QT Intervals | Day15 -0:30 (N=137, 137) | -1.76 mS | Standard Deviation 20.16 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QT Intervals | Day15 0:10 (N=135, 136) | 0.53 mS | Standard Deviation 21.28 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QT Intervals | Day29 0:10 (N=132, 135) | -1.73 mS | Standard Deviation 20.83 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QT Intervals | Baseline | 381.33 mS | Standard Deviation 29.42 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QT Intervals | Day1 0:10 | 2.69 mS | Standard Deviation 13.82 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QT Intervals | Day1 1:00 (N=138, 138) | 2.33 mS | Standard Deviation 18.02 |
| Olo 5 µg + Tio5 µg | 12-lead ECG QT Intervals | Day29 -0:30 (N=134, 136) | -3.14 mS | Standard Deviation 20.13 |
Secondary
AUC (0-6H) FEV1 (Unsupervised), AUC (0-6H) PEFR (Unsupervised), FVC Peak (0-3h), AUC (6-12h) FEV1 (Unsupervised), AUC (6-12h) PEFR (Unsupervised), Individual PEFR Measurements (Supervised and Unsupervised), Individual PEFR Measurements (Unsupervised)
* AUC (0-6h) for FEV1, and PEFR (unsupervised) after first dose and after 2 and 4 weeks of treatment were not analysed in the study report because the pertinent information from the unsupervised Pulmonary Function Tests (PFTs) was for the time interval from 6 to 12 hours post-dosing. * FVC peak 0-3h response after the first dose and at Week 2 (supervised) and AUC (6-12h) for FEV1 and PEFR after the first dose and at Week 2 (unsupervised) were not analysed in the study report. * Individual PEFR (supervised) measurements and individual FEV1 and PEFR (unsupervised) measurements at each time point were not analysed in the study report.
Time frame: 4 weeks
Population: No patients analyzed in the study report.
Secondary
Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination
Clinically significant abnormalities for blood chemistry, haematology, urinalysis and physical examination
Time frame: 14 weeks
Population: Treated Set (TS) including all randomized patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination | Creatinine phosphokinase increased | 8 participants |
| Olo 2 µg + Tio 5 µg | Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination | Eosinophils increased | 3 participants |
| Olo 2 µg + Tio 5 µg | Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination | Urinalysis | 0 participants |
| Olo 5 µg + Tio5 µg | Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination | Creatinine phosphokinase increased | 7 participants |
| Olo 5 µg + Tio5 µg | Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination | Eosinophils increased | 3 participants |
| Olo 5 µg + Tio5 µg | Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination | Urinalysis | 0 participants |
Secondary
FEV1 AUC 0-3h, Response
FEV1 Area Under the Curve (AUC) 0-3h, response \[L\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | FEV1 AUC 0-3h, Response | Day 1 | 0.168 Litres | Standard Error 0.006 |
| Olo 2 µg + Tio 5 µg | FEV1 AUC 0-3h, Response | Day 15 | 0.174 Litres | Standard Error 0.012 |
| Olo 2 µg + Tio 5 µg | FEV1 AUC 0-3h, Response | Day 29 | 0.201 Litres | Standard Error 0.011 |
| Olo 5 µg + Tio5 µg | FEV1 AUC 0-3h, Response | Day 1 | 0.173 Litres | Standard Error 0.006 |
| Olo 5 µg + Tio5 µg | FEV1 AUC 0-3h, Response | Day 15 | 0.194 Litres | Standard Error 0.012 |
| Olo 5 µg + Tio5 µg | FEV1 AUC 0-3h, Response | Day 29 | 0.200 Litres | Standard Error 0.011 |
Comparison: Test Day 1. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.519895% CI: [-0.01, 0.021]ANCOVA
Comparison: Test Day 15. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)p-value: 0.21195% CI: [-0.011, 0.051]ANCOVA
Comparison: Test day 29. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)p-value: 0.936895% CI: [-0.029, 0.027]ANCOVA
Secondary
FEV1, AUC (0-6h) Response
FEV1, AUC (0-6h) response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | FEV1, AUC (0-6h) Response | 0.202 Litres | Standard Error 0.012 |
| Olo 5 µg + Tio5 µg | FEV1, AUC (0-6h) Response | 0.206 Litres | Standard Error 0.012 |
Comparison: Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.790695% CI: [-0.026, 0.034]ANCOVA
Secondary
FEV1 Peak 0-3h Response
FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response \[L\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | FEV1 Peak 0-3h Response | Day 1 | 0.269 Litres | Standard Error 0.008 |
| Olo 2 µg + Tio 5 µg | FEV1 Peak 0-3h Response | Day 15 | 0.257 Litres | Standard Error 0.014 |
| Olo 2 µg + Tio 5 µg | FEV1 Peak 0-3h Response | Day 29 | 0.288 Litres | Standard Error 0.014 |
| Olo 5 µg + Tio5 µg | FEV1 Peak 0-3h Response | Day 1 | 0.262 Litres | Standard Error 0.008 |
| Olo 5 µg + Tio5 µg | FEV1 Peak 0-3h Response | Day 15 | 0.279 Litres | Standard Error 0.015 |
| Olo 5 µg + Tio5 µg | FEV1 Peak 0-3h Response | Day 29 | 0.294 Litres | Standard Error 0.014 |
Comparison: Test Day 1. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)p-value: 0.533995% CI: [-0.027, 0.014]ANCOVA
Comparison: Test day 15. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)p-value: 0.240895% CI: [-0.015, 0.058]ANCOVA
Comparison: Test day 29. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)p-value: 0.713995% CI: [-0.029, 0.042]ANCOVA
Secondary
FEV1 (Unsupervised) AUC (6-12h) Response
FEV1 (unsupervised) AUC (6-12h) response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 6 hours (h), 9h and 12h after drug administration on day 29
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | FEV1 (Unsupervised) AUC (6-12h) Response | 0.106 Litres | Standard Error 0.029 |
| Olo 5 µg + Tio5 µg | FEV1 (Unsupervised) AUC (6-12h) Response | 0.114 Litres | Standard Error 0.029 |
Comparison: Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.847395% CI: [-0.067, 0.082]ANCOVA
Secondary
FVC AUC (0-3h) Response
FVC AUC (0-3h) response \[L\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | FVC AUC (0-3h) Response | Day 1 | 0.273 Litres | Standard Error 0.012 |
| Olo 2 µg + Tio 5 µg | FVC AUC (0-3h) Response | Day 15 | 0.271 Litres | Standard Error 0.02 |
| Olo 2 µg + Tio 5 µg | FVC AUC (0-3h) Response | Day 29 | 0.275 Litres | Standard Error 0.021 |
| Olo 5 µg + Tio5 µg | FVC AUC (0-3h) Response | Day 1 | 0.275 Litres | Standard Error 0.012 |
| Olo 5 µg + Tio5 µg | FVC AUC (0-3h) Response | Day 15 | 0.308 Litres | Standard Error 0.021 |
| Olo 5 µg + Tio5 µg | FVC AUC (0-3h) Response | Day 29 | 0.303 Litres | Standard Error 0.022 |
Comparison: Test day 1. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)p-value: 0.938495% CI: [-0.029, 0.032]ANCOVA
Comparison: Test day 15. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.158395% CI: [-0.014, 0.088]ANCOVA
Comparison: Test day 29. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.291495% CI: [-0.025, 0.082]ANCOVA
Secondary
FVC AUC (0-6h) Response
FVC AUC (0-6h) response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | FVC AUC (0-6h) Response | 0.283 Litres | Standard Error 0.023 |
| Olo 5 µg + Tio5 µg | FVC AUC (0-6h) Response | 0.318 Litres | Standard Error 0.024 |
Comparison: Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.248595% CI: [-0.024, 0.094]ANCOVA
Secondary
FVC Peak 0-3h Response
FVC peak 0-3h response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 29
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | FVC Peak 0-3h Response | 0.444 Litres | Standard Error 0.033 |
| Olo 5 µg + Tio5 µg | FVC Peak 0-3h Response | 0.490 Litres | Standard Error 0.034 |
Comparison: Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.287595% CI: [-0.039, 0.13]ANCOVA
Secondary
Individual FEV1 Measurements
Individual FEV1 measurements \[L\] at each time point on Day 29. The presented means are adjusted.
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | -1:00 | 1.426 Litres | Standard Error 0.013 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | -0:10 | 1.434 Litres | Standard Error 0.014 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | 2:00 | 1.617 Litres | Standard Error 0.012 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | 3:00 | 1.601 Litres | Standard Error 0.015 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | 4:00 | 1.582 Litres | Standard Error 0.016 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | 0:05 | 1.497 Litres | Standard Error 0.014 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | 0:30 | 1.541 Litres | Standard Error 0.012 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | 1:00 | 1.570 Litres | Standard Error 0.012 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | 5:00 | 1.571 Litres | Standard Error 0.013 |
| Olo 2 µg + Tio 5 µg | Individual FEV1 Measurements | 6:00 | 1.547 Litres | Standard Error 0.013 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | 6:00 | 1.551 Litres | Standard Error 0.013 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | -1:00 | 1.417 Litres | Standard Error 0.013 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | -0:10 | 1.438 Litres | Standard Error 0.014 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | 1:00 | 1.570 Litres | Standard Error 0.012 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | 0:30 | 1.534 Litres | Standard Error 0.012 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | 2:00 | 1.614 Litres | Standard Error 0.012 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | 0:05 | 1.498 Litres | Standard Error 0.014 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | 3:00 | 1.606 Litres | Standard Error 0.015 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | 5:00 | 1.570 Litres | Standard Error 0.014 |
| Olo 5 µg + Tio5 µg | Individual FEV1 Measurements | 4:00 | 1.606 Litres | Standard Error 0.016 |
Secondary
Individual FVC Measurements
Individual FVC measurements \[L\] at each time point The categories correspond to the planned times for FVC measurements on Day 29. The presented means are adjusted.
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | 1:00 | 3.093 Litres | Standard Error 0.023 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | -0:10 | 2.892 Litres | Standard Error 0.024 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | 5:00 | 3.109 Litres | Standard Error 0.025 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | 0:05 | 3.009 Litres | Standard Error 0.024 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | 4:00 | 3.143 Litres | Standard Error 0.039 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | 0:30 | 3.067 Litres | Standard Error 0.023 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | 2:00 | 3.154 Litres | Standard Error 0.023 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | 6:00 | 3.061 Litres | Standard Error 0.023 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | 3:00 | 3.147 Litres | Standard Error 0.037 |
| Olo 2 µg + Tio 5 µg | Individual FVC Measurements | -1:00 | 2.894 Litres | Standard Error 0.023 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | 6:00 | 3.083 Litres | Standard Error 0.023 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | 1:00 | 3.112 Litres | Standard Error 0.023 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | 3:00 | 3.201 Litres | Standard Error 0.038 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | 4:00 | 3.204 Litres | Standard Error 0.04 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | 5:00 | 3.131 Litres | Standard Error 0.025 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | -1:00 | 2.899 Litres | Standard Error 0.024 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | -0:10 | 2.907 Litres | Standard Error 0.024 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | 0:05 | 3.032 Litres | Standard Error 0.025 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | 2:00 | 3.189 Litres | Standard Error 0.023 |
| Olo 5 µg + Tio5 µg | Individual FVC Measurements | 0:30 | 3.083 Litres | Standard Error 0.024 |
Secondary
Overall Marked Changes From Baseline in Vital Signs
Overall marked changes from baseline in systolic blood pressure, diastolic blood pressure and pulse rate.
Time frame: Baseline to week 14
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Overall Marked Changes From Baseline in Vital Signs | Diastolic blood pressure decreased | 13 participants |
| Olo 2 µg + Tio 5 µg | Overall Marked Changes From Baseline in Vital Signs | Diastolic blood pressure increased | 19 participants |
| Olo 2 µg + Tio 5 µg | Overall Marked Changes From Baseline in Vital Signs | Systolic blood pressure increased | 16 participants |
| Olo 2 µg + Tio 5 µg | Overall Marked Changes From Baseline in Vital Signs | Systolic blood pressure decreased | 10 participants |
| Olo 2 µg + Tio 5 µg | Overall Marked Changes From Baseline in Vital Signs | Pulse rate increased | 10 participants |
| Olo 2 µg + Tio 5 µg | Overall Marked Changes From Baseline in Vital Signs | Pulse rate decreased | 19 participants |
| Olo 5 µg + Tio5 µg | Overall Marked Changes From Baseline in Vital Signs | Diastolic blood pressure increased | 15 participants |
| Olo 5 µg + Tio5 µg | Overall Marked Changes From Baseline in Vital Signs | Pulse rate increased | 13 participants |
| Olo 5 µg + Tio5 µg | Overall Marked Changes From Baseline in Vital Signs | Systolic blood pressure decreased | 11 participants |
| Olo 5 µg + Tio5 µg | Overall Marked Changes From Baseline in Vital Signs | Systolic blood pressure increased | 23 participants |
| Olo 5 µg + Tio5 µg | Overall Marked Changes From Baseline in Vital Signs | Pulse rate decreased | 10 participants |
| Olo 5 µg + Tio5 µg | Overall Marked Changes From Baseline in Vital Signs | Diastolic blood pressure decreased | 17 participants |
Secondary
Patient Global Rating
Patient global rating scores treatment comparison after 4 weeks The score was evaluated on a 7-point scale : * 1 : very much better * 2 : much better * 3 : a little better * 4 : no change * 5 : a little worse * 6 : much worse * 7 : very much worse The presented means are adjusted.
Time frame: 4 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Patient Global Rating | 3.207 units on a scale | Standard Error 0.091 |
| Olo 5 µg + Tio5 µg | Patient Global Rating | 3.093 units on a scale | Standard Error 0.09 |
Comparison: Based on a ANCOVA with terms for treatment, centre, patient within centre and period (all effects fixed).p-value: 0.326995% CI: [-0.342, 0.115]ANCOVA
Secondary
PEFR AUC (0-3h) Response
Peak Expiratory Flow Rate (PEFR) AUC (0-3h) response \[L/min\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | PEFR AUC (0-3h) Response | Day 15 | 27.817 Litres / minute | Standard Error 2.483 |
| Olo 2 µg + Tio 5 µg | PEFR AUC (0-3h) Response | Day 1 | 27.159 Litres / minute | Standard Error 1.604 |
| Olo 2 µg + Tio 5 µg | PEFR AUC (0-3h) Response | Day 29 | 32.395 Litres / minute | Standard Error 2.101 |
| Olo 5 µg + Tio5 µg | PEFR AUC (0-3h) Response | Day 15 | 34.128 Litres / minute | Standard Error 2.507 |
| Olo 5 µg + Tio5 µg | PEFR AUC (0-3h) Response | Day 1 | 28.143 Litres / minute | Standard Error 1.619 |
| Olo 5 µg + Tio5 µg | PEFR AUC (0-3h) Response | Day 29 | 33.947 Litres / minute | Standard Error 2.121 |
Comparison: Test day 1. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.629995% CI: [-3.046, 5.015]ANCOVA
Comparison: Test day 15. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.047595% CI: [0.07, 12.553]ANCOVA
Comparison: Test day 29. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.56295% CI: [-3.729, 6.833]ANCOVA
Secondary
PEFR AUC (6-12h) Response
PEFR AUC (6-12h) response \[L\] on day 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1 hour (h) and 10 minutes before drug administration on day 1 and 6h, 9h and 12h after drug administration on day 29
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | PEFR AUC (6-12h) Response | 24.830 Litres / minute | Standard Error 3.634 |
| Olo 5 µg + Tio5 µg | PEFR AUC (6-12h) Response | 24.130 Litres / minute | Standard Error 3.599 |
Comparison: Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.880895% CI: [-9.914, 8.514]ANCOVA
Secondary
PEFR Peak 0-3h Response
PEFR peak 0-3h response \[L/min\] on days 1, 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | PEFR Peak 0-3h Response | Day 1 | 49.125 Litres / minute | Standard Error 1.843 |
| Olo 2 µg + Tio 5 µg | PEFR Peak 0-3h Response | Day 15 | 46.355 Litres / minute | Standard Error 2.801 |
| Olo 2 µg + Tio 5 µg | PEFR Peak 0-3h Response | Day 29 | 52.497 Litres / minute | Standard Error 2.466 |
| Olo 5 µg + Tio5 µg | PEFR Peak 0-3h Response | Day 1 | 48.946 Litres / minute | Standard Error 1.861 |
| Olo 5 µg + Tio5 µg | PEFR Peak 0-3h Response | Day 15 | 52.835 Litres / minute | Standard Error 2.827 |
| Olo 5 µg + Tio5 µg | PEFR Peak 0-3h Response | Day 29 | 55.596 Litres / minute | Standard Error 2.49 |
Comparison: Test day 1. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.939195% CI: [-4.812, 4.454]ANCOVA
Comparison: Test day 15. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.070995% CI: [-0.56, 13.52]ANCOVA
Comparison: Test day 29. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.324595% CI: [-3.1, 9.298]ANCOVA
Secondary
Physician's Global Evaluation
Physician's global evaluation score on days 15 and 29 The score was evaluated on a 8-points scale : * Poor : 1,2 * Fair : 3,4 * Good : 5,6 * Excellent : 7,8 The presented means are adjusted
Time frame: Days 15 and 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Physician's Global Evaluation | Day 29 | 5.085 units on a scale | Standard Error 0.063 |
| Olo 2 µg + Tio 5 µg | Physician's Global Evaluation | Day 15 | 5.084 units on a scale | Standard Error 0.07 |
| Olo 5 µg + Tio5 µg | Physician's Global Evaluation | Day 15 | 5.079 units on a scale | Standard Error 0.07 |
| Olo 5 µg + Tio5 µg | Physician's Global Evaluation | Day 29 | 5.065 units on a scale | Standard Error 0.063 |
Comparison: Test day 15. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.955795% CI: [-0.181, 0.171]ANCOVA
Comparison: Test day 29. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.809695% CI: [-0.178, 0.14]ANCOVA
Secondary
Trough FEV1 Response [L] After 2 Weeks of Treatment
Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Trough FEV1 Response [L] After 2 Weeks of Treatment | 0.037 Litres | Standard Error 0.015 |
| Olo 5 µg + Tio5 µg | Trough FEV1 Response [L] After 2 Weeks of Treatment | 0.059 Litres | Standard Error 0.015 |
Comparison: Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.242595% CI: [-0.015, 0.061]ANCOVA
Secondary
Trough FVC Response
Trough Forced Vital Capacity (FVC) response \[L\] on days 15 and 29. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).
Time frame: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15, in addition 4h, 5h, 6h after drug administration on day 29
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Trough FVC Response | Day 15 | 0.072 Litres | Standard Error 0.024 |
| Olo 2 µg + Tio 5 µg | Trough FVC Response | Day 29 | 0.066 Litres | Standard Error 0.022 |
| Olo 5 µg + Tio5 µg | Trough FVC Response | Day 15 | 0.104 Litres | Standard Error 0.025 |
| Olo 5 µg + Tio5 µg | Trough FVC Response | Day 29 | 0.076 Litres | Standard Error 0.023 |
Comparison: Test Day 15. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.294495% CI: [-0.029, 0.094]ANCOVA
Comparison: Test day 29. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.71895% CI: [-0.046, 0.066]ANCOVA
Secondary
Weekly Mean Evening PEFR
Weekly mean evening PEFR \[L/min\] on weeks 1,2,3 and 4. The presented means are adjusted.
Time frame: Weeks 1,2,3 and 4
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Weekly Mean Evening PEFR | Week 1 | 262.21 Litres / minute | Standard Error 2.026 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Evening PEFR | Week 2 | 261.08 Litres / minute | Standard Error 2.146 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Evening PEFR | Week 3 | 258.62 Litres / minute | Standard Error 1.959 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Evening PEFR | Week 4 | 261.38 Litres / minute | Standard Error 1.942 |
| Olo 5 µg + Tio5 µg | Weekly Mean Evening PEFR | Week 4 | 260.34 Litres / minute | Standard Error 1.94 |
| Olo 5 µg + Tio5 µg | Weekly Mean Evening PEFR | Week 1 | 265.51 Litres / minute | Standard Error 2.024 |
| Olo 5 µg + Tio5 µg | Weekly Mean Evening PEFR | Week 3 | 260.32 Litres / minute | Standard Error 1.956 |
| Olo 5 µg + Tio5 µg | Weekly Mean Evening PEFR | Week 2 | 262.47 Litres / minute | Standard Error 2.144 |
Comparison: Test Week 1. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.203795% CI: [-1.813, 8.418]ANCOVA
Comparison: Test Week 2. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.611895% CI: [-4.027, 6.813]ANCOVA
Comparison: Test Week 3. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.498895% CI: [-3.251, 6.64]ANCOVA
Comparison: Test Week 4. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.675795% CI: [-5.944, 3.865]ANCOVA
Secondary
Weekly Mean Morning PEFR
Weekly mean morning PEFR \[L/min\] on weeks 1,2,3 and 4. The presented means are adjusted.
Time frame: Weeks 1,2,3 and 4
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Weekly Mean Morning PEFR | Week 1 | 244.16 Litres / minute | Standard Error 1.713 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Morning PEFR | Week 3 | 242.31 Litres / minute | Standard Error 1.805 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Morning PEFR | Week 2 | 242.38 Litres / minute | Standard Error 1.842 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Morning PEFR | Week 4 | 242.90 Litres / minute | Standard Error 2 |
| Olo 5 µg + Tio5 µg | Weekly Mean Morning PEFR | Week 2 | 243.72 Litres / minute | Standard Error 1.821 |
| Olo 5 µg + Tio5 µg | Weekly Mean Morning PEFR | Week 1 | 245.28 Litres / minute | Standard Error 1.693 |
| Olo 5 µg + Tio5 µg | Weekly Mean Morning PEFR | Week 4 | 244.56 Litres / minute | Standard Error 1.977 |
| Olo 5 µg + Tio5 µg | Weekly Mean Morning PEFR | Week 3 | 242.97 Litres / minute | Standard Error 1.784 |
Comparison: Test week 1. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.608195% CI: [-3.19, 5.429]ANCOVA
Comparison: Test Week 2. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.568695% CI: [-3.296, 5.973]ANCOVA
Comparison: Test Week 3. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.776595% CI: [-3.888, 5.194]ANCOVA
Comparison: Test Week 4. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.516695% CI: [-3.379, 6.686]ANCOVA
Secondary
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol])
Weekly mean number of occasions of rescue therapy used per day (as occasion require (PRN) salbutamol \[albuterol\]) on weeks 1,2,3 and 4. The means presented are the adjusted mean of weekly mean.
Time frame: Weeks 1,2,3 and 4
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olo 2 µg + Tio 5 µg | Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Week 1 | 1.294 number of occasions / day | Standard Error 0.063 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Week 3 | 1.369 number of occasions / day | Standard Error 0.071 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Week 2 | 1.472 number of occasions / day | Standard Error 0.068 |
| Olo 2 µg + Tio 5 µg | Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Week 4 | 1.403 number of occasions / day | Standard Error 0.071 |
| Olo 5 µg + Tio5 µg | Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Week 2 | 1.352 number of occasions / day | Standard Error 0.067 |
| Olo 5 µg + Tio5 µg | Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Week 1 | 1.305 number of occasions / day | Standard Error 0.062 |
| Olo 5 µg + Tio5 µg | Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Week 4 | 1.363 number of occasions / day | Standard Error 0.069 |
| Olo 5 µg + Tio5 µg | Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) | Week 3 | 1.367 number of occasions / day | Standard Error 0.07 |
Comparison: Test Week 1. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.890195% CI: [-0.147, 0.169]ANCOVA
Comparison: Test Week 2. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.164795% CI: [-0.29, 0.05]ANCOVA
Comparison: Test Week 3. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.982295% CI: [-0.18, 0.176]ANCOVA
Comparison: Test Week 4. Based on a ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).p-value: 0.654295% CI: [-0.218, 0.137]ANCOVA