Asthma
Conditions
Brief summary
The purpose of this study is to assess peak FEV1 of two doses of QVM149 compared to a fixed-dose combination of salmeterol/fluticasone (50/500μg b.i.d.) and to characterize the respective 24 hour bronchodilator effect profiles in patients with asthma. Data from this study will complement lung function data obtained in the pivotal QVM149 phase 3 program by assessing the bronchodilatory effect of QVM149 at multiple time-points over an entire dosing interval of 24 hours.
Interventions
DRUGQVM149 150/50/80 μg o.d.
A
DRUGQVM149 150/50/160 μg o.d.
B
DRUGsalmeterol/fluticasone FDC 50/500 μg b.i.d.
C
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion criteria * Male and female adult patients ≥ 18 years old and ≤ 75 years. * Patients with a documented physician diagnosis of asthma for a period of at least 12 months prior to Visit 1 (Screening). * Patients who have used ICS and LABA combinations for asthma for at least 3 month and at a stable medium or high dose of ICS for at least 1 month prior to Visit 1 (Screening). * Pre-bronchodilator FEV1 of \< 80 % of the predicted normal value at screening Visit 1 (spirometry will not be repeated at baseline prior to randomization). * Patients who demonstrate an increase in FEV1 of ≥ 12 % and 200 mL after administration of 400 µg salbutamol/360 µg albuterol (or equivalent do se) at Visit 1 (Screening). All patients must perform a reversibility test at Visit 1 (Screening). If reversibility is not demonstrated at Visit 1 (Screening), then, reversibility testing may be repeated once during the screening period. * If reversibility is not demonstrated at Visit 1 (retesting allowed once), patients must be screen failed. Spacer devices are not permitted during reversibility testing Key
Exclusion criteria
* Patients who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1 * Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 * Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder-neck obstruction or severe renal impairment or urinary retention * Patients who have had a respiratory tract infection or asthma worsening within 4 weeks prior to Visit 1 * Patients with any chronic conditions affecting the upper respiratory tract * Patients with a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis. * Patients with Type I diabetes or uncontrolled Type II diabetes (HbA1c \>9% at screening). * Patients who have a clinically significant ECG abnormality at Visit 1 * Patients with a history of hypersensitivity or intolerance to any of the study drugs (including excipients) * Patients with narcolepsy and/or insomnia. * Patients on Maintenance Immunotherapy (desensitization) for allergies for less than 3 months prior to Visit 2 or patients on Maintenance Immunotherapy for more than 3 months prior to Visit 2 but expected to change throughout the course of the study. * Pregnant or nursing (lactating) women * Women of child-bearing potential must use Highly effective contraception methods * Patients who have discontinued LAMA therapy in the past for any safety, tolerability or perceived lack of efficacy reason. * History of paradoxical bronchospasm in response to inhaled medicines. * Patients with a history of clinically relevant bronchoconstriction upon repeated forced expiratory maneuvers. * Patient with a serum potassium level below the laboratory limit of normal at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak FEV1 (L) Defined as the Highest Bronchodilatory Effect on FEV1 During a Period of 5 Min to 4 h After the Last Evening Dose of Each Treatment Period | 3 weeks | The highest bronchodilator effect on FEV1 during a period of 5 min to 4 h after the last evening dose of each treatment period . To demonstrate superiority in peak bronchodilator effect of QVM149 at a dose of 150/50/160 μg o.d. and 150/50/80 μg o.d. compared to a FDC of salmeterol/fluticasone at a dose of 50/500 μg b.i.d. after 3 weeks of treatment in patients with asthma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks | To evaluate the bronchodilator effect of each dose of QVM149 compared to salmeterol/fluticasone FDC after 3 weeks of treatment at -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min. |
| FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks | To evaluate the bronchodilator effect of each dose of QVM149 compared to salmeterol/fluticasone FDC after 3 weeks of treatment at -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min. |
| FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks | To evaluate the bronchodilator effect of each dose of QVM149 compared to salmeterol/fluticasone FDC after 3 weeks of treatment at -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min. |
| FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | 3 weeks | To evaluate the bronchodilator effect of each dose of QVM149 compared to salmeterol/ fluticasone FDC by measuring standardized FEV1 AUCs after 3 weeks of treatment respective period. |
| Trough FEV1 After 21 Days of Treatment | 3 weeks | To evaluate post-dose trough bronchodilator effect of each dose of QVM149 compared to salmeterol/fluticasone FDC after 3 weeks of treatment in the respective treatment period. The trough FEV1 is the mean value of FEV1 at 23 h 15 min and 23 h 45 min post-dose |
Countries
Bulgaria, China, Germany, Netherlands, Romania, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants randomized to one of six treatment sequences | 116 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Non-compliance with study treatment | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | subject/guardian decision | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | technical problems | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 49.5 Years STANDARD_DEVIATION 14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 106 Participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 112 | 0 / 115 | 0 / 111 |
| other Total, other adverse events | 14 / 112 | 18 / 115 | 21 / 111 |
| serious Total, serious adverse events | 0 / 112 | 0 / 115 | 0 / 111 |
Outcome results
Primary
Peak FEV1 (L) Defined as the Highest Bronchodilatory Effect on FEV1 During a Period of 5 Min to 4 h After the Last Evening Dose of Each Treatment Period
The highest bronchodilator effect on FEV1 during a period of 5 min to 4 h after the last evening dose of each treatment period . To demonstrate superiority in peak bronchodilator effect of QVM149 at a dose of 150/50/160 μg o.d. and 150/50/80 μg o.d. compared to a FDC of salmeterol/fluticasone at a dose of 50/500 μg b.i.d. after 3 weeks of treatment in patients with asthma
Time frame: 3 weeks
Population: Pharmacodynamics set - The PD analysis set included all patients with any available PD data, who received any study treatment and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVM149 150/50/160 μg o.d. | Peak FEV1 (L) Defined as the Highest Bronchodilatory Effect on FEV1 During a Period of 5 Min to 4 h After the Last Evening Dose of Each Treatment Period | 2.792 Liters | Standard Error 0.075 |
| QVM149 150/50/80 μg o.d. | Peak FEV1 (L) Defined as the Highest Bronchodilatory Effect on FEV1 During a Period of 5 Min to 4 h After the Last Evening Dose of Each Treatment Period | 2.779 Liters | Standard Error 0.075 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | Peak FEV1 (L) Defined as the Highest Bronchodilatory Effect on FEV1 During a Period of 5 Min to 4 h After the Last Evening Dose of Each Treatment Period | 2.620 Liters | Standard Error 0.075 |
p-value: <0.000195% CI: [0.137, 0.208]Mixed Models Analysis
p-value: <0.000195% CI: [0.123, 0.195]Mixed Models Analysis
Secondary
FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21)
To evaluate the bronchodilator effect of each dose of QVM149 compared to salmeterol/ fluticasone FDC by measuring standardized FEV1 AUCs after 3 weeks of treatment respective period.
Time frame: 3 weeks
Population: Pharmacodynamics set - The PD analysis set included all patients with any available PD data, who received any study treatment and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 150/50/160 μg o.d. | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 4 h | 2.687 Liters | Standard Error 0.0741 |
| QVM149 150/50/160 μg o.d. | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 1 h | 2.673 Liters | Standard Error 0.0735 |
| QVM149 150/50/160 μg o.d. | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 23 h 45 min | 2.677 Liters | Standard Error 0.0766 |
| QVM149 150/50/80 μg o.d. | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 4 h | 2.669 Liters | Standard Error 0.0741 |
| QVM149 150/50/80 μg o.d. | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 1 h | 2.644 Liters | Standard Error 0.0736 |
| QVM149 150/50/80 μg o.d. | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 23 h 45 min | 2.652 Liters | Standard Error 0.0768 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 1 h | 2.513 Liters | Standard Error 0.0737 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 23 h 45 min | 2.515 Liters | Standard Error 0.0768 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21) | FEV1 AUC 5 min - 4 h | 2.510 Liters | Standard Error 0.0742 |
Secondary
FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose
To evaluate the bronchodilator effect of each dose of QVM149 compared to salmeterol/fluticasone FDC after 3 weeks of treatment at -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min.
Time frame: -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks
Population: Pharmacodynamics set - The PD analysis set included all patients with any available PD data, who received any study treatment and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18h | 0.6801 Ratio | Standard Deviation 0.09943 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2h | 0.6939 Ratio | Standard Deviation 0.09629 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1h | 0.6900 Ratio | Standard Deviation 0.09764 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5min | 0.6788 Ratio | Standard Deviation 0.103 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3h | 0.6968 Ratio | Standard Deviation 0.10159 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 15min | 06821 Ratio | Standard Deviation 0.10386 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15min | 0.6707 Ratio | Standard Deviation 0.10646 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4h | 0.6897 Ratio | Standard Deviation 0.1006 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14h | 0.6846 Ratio | Standard Deviation 0.10842 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45min | 0.6701 Ratio | Standard Deviation 0.1088 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8h | 0.6842 Ratio | Standard Deviation 0.10782 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 45min | 0.6782 Ratio | Standard Deviation 0.10457 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15min | 0.6873 Ratio | Standard Deviation 0.10126 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10h | 0.6916 Ratio | Standard Deviation 0.1055 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21h | 0.6790 Ratio | Standard Deviation 0.1089 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30min | 0.6878 Ratio | Standard Deviation 0.10137 |
| QVM149 150/50/160 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55min | 0.6853 Ratio | Standard Deviation 0.10672 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45min | 0.6612 Ratio | Standard Deviation 0.10358 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14h | 0.6848 Ratio | Standard Deviation 0.1045 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30min | 0.6844 Ratio | Standard Deviation 0.10699 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18h | 0.6741 Ratio | Standard Deviation 0.1024 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15min | 0.6669 Ratio | Standard Deviation 0.10422 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21h | 0.6785 Ratio | Standard Deviation 0.10387 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 15min | 0.6791 Ratio | Standard Deviation 0.09986 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1h | 0.6895 Ratio | Standard Deviation 0.0994 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 45min | 0.6776 Ratio | Standard Deviation 0.10111 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55min | 0.6791 Ratio | Standard Deviation 0.10656 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2h | 0.6932 Ratio | Standard Deviation 0.10073 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3h | 0.6890 Ratio | Standard Deviation 0.10052 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5min | 0.6754 Ratio | Standard Deviation 0.1037 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4h | 0.6879 Ratio | Standard Deviation 0.09733 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8h | 0.6802 Ratio | Standard Deviation 0.11349 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10h | 0.6858 Ratio | Standard Deviation 0.10468 |
| QVM149 150/50/80 μg o.d. | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15min | 0.6778 Ratio | Standard Deviation 0.10734 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 45min | 0.6537 Ratio | Standard Deviation 0.10934 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45min | 0.6527 Ratio | Standard Deviation 0.10867 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15min | 0.6539 Ratio | Standard Deviation 0.10526 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5min | 0.6563 Ratio | Standard Deviation 0.10639 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15min | 0.6560 Ratio | Standard Deviation 0.10823 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30min | 0.6573 Ratio | Standard Deviation 0.10552 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1h | 0.6632 Ratio | Standard Deviation 0.10403 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2h | 0.6647 Ratio | Standard Deviation 0.10413 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3h | 0.6634 Ratio | Standard Deviation 0.10436 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4h | 0.6605 Ratio | Standard Deviation 0.10419 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8h | 0.6492 Ratio | Standard Deviation 0.10814 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10h | 0.6489 Ratio | Standard Deviation 0.11155 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55min | 0.6482 Ratio | Standard Deviation 0.1081 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14h | 0.6567 Ratio | Standard Deviation 0.11048 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18h | 0.6546 Ratio | Standard Deviation 0.10369 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21h | 0.6562 Ratio | Standard Deviation 0.10729 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 15min | 0.6548 Ratio | Standard Deviation 0.10423 |
Secondary
FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose
To evaluate the bronchodilator effect of each dose of QVM149 compared to salmeterol/fluticasone FDC after 3 weeks of treatment at -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min.
Time frame: -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks
Population: Pharmacodynamics set - The PD analysis set included all patients with any available PD data, who received any study treatment and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55 min | 2.7042 Liters | Standard Error 0.07486 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2 h | 2.7033 Liters | Standard Error 0.07441 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15 min | 2.6023 Liters | Standard Error 0.07479 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45 min | 2.6237 Liters | Standard Error 0.07505 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3 h | 2.6995 Liters | Standard Error 0.07449 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21 h | 2.6113 Liters | Standard Error 0.07466 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10 h | 2.6999 Liters | Standard Error 0.07489 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4 h | 2.6815 Liters | Standard Error 0.07482 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15 min | 2.6696 Liters | Standard Error 0.07531 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8 h | 2.6801 Liters | Standard Error 0.07454 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23 h 45 min | 2.5966 Liters | Standard Error 0.07433 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18 h | 2.6345 Liters | Standard Error 0.07451 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30 min | 2.6873 Liters | Standard Error 0.07444 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23 h 15 min | 2.6143 Liters | Standard Error 0.07433 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14 h | 2.6829 Liters | Standard Error 0.07456 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1 h | 2.6922 Liters | Standard Error 0.0743 |
| QVM149 150/50/160 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5 min | 2.6412 Liters | Standard Error 0.07446 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10 h | 2.6796 Liters | Standard Error 0.07494 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45 min | 2.5639 Liters | Standard Error 0.07503 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15 min | 2.5630 Liters | Standard Error 0.07478 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5 min | 2.6179 Liters | Standard Error 0.07445 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15 min | 2.6137 Liters | Standard Error 0.07532 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30 min | 2.6504 Liters | Standard Error 0.07444 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1 h | 2.6825 Liters | Standard Error 0.07431 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2 h | 2.6996 Liters | Standard Error 0.07443 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3 h | 2.6719 Liters | Standard Error 0.0745 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4 h | 2.6565 Liters | Standard Error 0.07484 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8 h | 2.6550 Liters | Standard Error 0.07459 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55 min | 2.6641 Liters | Standard Error 0.0749 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14 h | 2.6541 Liters | Standard Error 0.07459 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18 h | 2.6073 Liters | Standard Error 0.07455 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21 h | 2.5989 Liters | Standard Error 0.07472 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23 h 15 min | 2.5950 Liters | Standard Error 0.07438 |
| QVM149 150/50/80 μg o.d. | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23 h 45 min | 2.5722 Liters | Standard Error 0.07438 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15 min | 2.4835 Liters | Standard Error 0.0748 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55 min | 2.4841 Liters | Standard Error 0.07491 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30 min | 2.5286 Liters | Standard Error 0.07444 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23 h 45 min | 2.4913 Liters | Standard Error 0.07439 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14 h | 2.5354 Liters | Standard Error 0.07461 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15 min | 2.5172 Liters | Standard Error 0.07533 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23 h 15 min | 2.4854 Liters | Standard Error 0.07439 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18 h | 2.5329 Liters | Standard Error 0.07457 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5 min | 2.5035 Liters | Standard Error 0.07446 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45 min | 2.4931 Liters | Standard Error 0.07505 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4 h | 2.5164 Liters | Standard Error 0.07485 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21 h | 2.5133 Liters | Standard Error 0.07475 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8 h | 2.4918 Liters | Standard Error 0.07459 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3 h | 2.5296 Liters | Standard Error 0.07451 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2 h | 2.5244 Liters | Standard Error 0.07443 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10 h | 2.4908 Liters | Standard Error 0.07495 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1 h | 2.5398 Liters | Standard Error 0.07431 |
Secondary
FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose
To evaluate the bronchodilator effect of each dose of QVM149 compared to salmeterol/fluticasone FDC after 3 weeks of treatment at -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min.
Time frame: -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks
Population: Pharmacodynamics set - The PD analysis set included all patients with any available PD data, who received any study treatment and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55min | 3.9271 Liters | Standard Deviation 0.98924 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2h | 3.8698 Liters | Standard Deviation 0.99623 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15min | 3.8743 Liters | Standard Deviation 1.04318 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45min | 3.9046 Liters | Standard Deviation 1.03169 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3h | 3.8576 Liters | Standard Deviation 0.98598 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21h | 3.8438 Liters | Standard Deviation 1.00672 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10h | 3.8976 Liters | Standard Deviation 0.9836 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4h | 3.8744 Liters | Standard Deviation 0.99833 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15min | 3.8669 Liters | Standard Deviation 0.98489 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8h | 3.9020 Liters | Standard Deviation 0.98241 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 45min | 3.8034 Liters | Standard Deviation 0.99036 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18h | 3.8675 Liters | Standard Deviation 0.95725 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30min | 3.8700 Liters | Standard Deviation 0.99289 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 15min | 3.7997 Liters | Standard Deviation 0.9755 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14h | 3.9091 Liters | Standard Deviation 1.00241 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1h | 3.8756 Liters | Standard Deviation 0.99978 |
| QVM149 150/50/160 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5min | 3.8656 Liters | Standard Deviation 0.99877 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10h | 3.9504 Liters | Standard Deviation 0.99286 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45min | 3.8538 Liters | Standard Deviation 0.98086 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15min | 3.8571 Liters | Standard Deviation 0.9742 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5min | 3.8976 Liters | Standard Deviation 1.00323 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15min | 3.8971 Liters | Standard Deviation 0.9684 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30min | 3.9002 Liters | Standard Deviation 0.99091 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1h | 3.8993 Liters | Standard Deviation 0.99141 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2h | 3.8985 Liters | Standard Deviation 0.99369 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3h | 3.8766 Liters | Standard Deviation 0.97806 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4h | 3.8627 Liters | Standard Deviation 0.95673 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8h | 3.9217 Liters | Standard Deviation 0.99184 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55min | 3.9405 Liters | Standard Deviation 1.00198 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14h | 3.9210 Liters | Standard Deviation 0.97942 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18h | 3.9151 Liters | Standard Deviation 1.02198 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21h | 3.8694 Liters | Standard Deviation 0.98786 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 15min | 3.8673 Liters | Standard Deviation 0.99915 |
| QVM149 150/50/80 μg o.d. | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 45min | 3.8603 Liters | Standard Deviation 0.98502 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -15min | 3.7230 Liters | Standard Deviation 0.9418 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 11h 55min | 3.7911 Liters | Standard Deviation 0.99102 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 30min | 3.7695 Liters | Standard Deviation 0.96026 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 45min | 3.7431 Liters | Standard Deviation 1.00668 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 14h | 3.8089 Liters | Standard Deviation 1.02918 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 15min | 3.7290 Liters | Standard Deviation 0.94033 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 23h 15min | 3.7395 Liters | Standard Deviation 1.01764 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 18h | 3.7824 Liters | Standard Deviation 0.98395 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 5min | 3.7536 Liters | Standard Deviation 0.93696 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | -45min | 3.7626 Liters | Standard Deviation 1.00067 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 4h | 3.7629 Liters | Standard Deviation 0.98205 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 21h | 3.7680 Liters | Standard Deviation 1.00768 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 8h | 3.7683 Liters | Standard Deviation 1.0041 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 3h | 3.7575 Liters | Standard Deviation 0.96899 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 2h | 3.7629 Liters | Standard Deviation 0.97164 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 10h | 3.7809 Liters | Standard Deviation 0.98213 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose | 1h | 3.7530 Liters | Standard Deviation 0.97083 |
Secondary
Trough FEV1 After 21 Days of Treatment
To evaluate post-dose trough bronchodilator effect of each dose of QVM149 compared to salmeterol/fluticasone FDC after 3 weeks of treatment in the respective treatment period. The trough FEV1 is the mean value of FEV1 at 23 h 15 min and 23 h 45 min post-dose
Time frame: 3 weeks
Population: Pharmacodynamics set - The PD analysis set included all patients with any available PD data, who received any study treatment and experienced no protocol deviations with relevant impact on PD data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVM149 150/50/160 μg o.d. | Trough FEV1 After 21 Days of Treatment | 2.623 Liters | Standard Error 0.0756 |
| QVM149 150/50/80 μg o.d. | Trough FEV1 After 21 Days of Treatment | 2.6046 Liters | Standard Error 0.0757 |
| Salmeterol/Fluticasone 50/500 µg b.i.d | Trough FEV1 After 21 Days of Treatment | 2.4998 Liters | Standard Error 0.0757 |
p-value: <0.000195% CI: [0.086, 0.161]Mixed Models Analysis