Assess Bronchodilator Effect and Safety of Two Doses of QVM149 Compared to a Fixed Dose Combination of Salmeterol/Fluticasone in Patients With Asthma.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Sequence 1 A-B-C |
Drug: QVM149 150/50/80 μg o.d.
A
Drug: QVM149 150/50/160 μg o.d.
B
Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.
C
|
| Active Comparator: Sequence 2 A-C-B |
Drug: QVM149 150/50/80 μg o.d.
A
Drug: QVM149 150/50/160 μg o.d.
B
Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.
C
|
| Active Comparator: Sequence 3 B-C-A |
Drug: QVM149 150/50/80 μg o.d.
A
Drug: QVM149 150/50/160 μg o.d.
B
Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.
C
|
| Active Comparator: Sequence 4 B-A-C |
Drug: QVM149 150/50/80 μg o.d.
A
Drug: QVM149 150/50/160 μg o.d.
B
Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.
C
|
| Active Comparator: Sequence 5 C-A-B |
Drug: QVM149 150/50/80 μg o.d.
A
Drug: QVM149 150/50/160 μg o.d.
B
Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.
C
|
| Active Comparator: Sequence 6 C-B-A |
Drug: QVM149 150/50/80 μg o.d.
A
Drug: QVM149 150/50/160 μg o.d.
B
Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.
C
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Sofia | Bulgaria | 1612 | |
| 2 | Novartis Investigative Site | Chang Chun | Jilin | China | 130021 |
| 3 | Novartis Investigative Site | Tianjin | Tianjin | China | 300192 |
| 4 | Novartis Investigative Site | Shanghai | China | 200433 | |
| 5 | Novartis Investigative Site | Berlin | Germany | 10117 | |
| 6 | Novartis Investigative Site | Frankfurt | Germany | 60596 | |
| 7 | Novartis Investigative Site | Grosshansdorf | Germany | 22947 | |
| 8 | Novartis Investigative Site | Hannover | Germany | 30625 | |
| 9 | Novartis Investigative Site | Wiesbaden | Germany | 65187 | |
| 10 | Novartis Investigative Site | Groningen | GZ | Netherlands | 9713 |
| 11 | Novartis Investigative Site | Bucharest | Romania | ||
| 12 | Novartis Investigative Site | Manchester | United Kingdom | M23 9QZ |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- CQVM149B2208
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Sequence 1 (A-B-C) | Sequence 2(A-C-B) | Sequence 3(B-C-A) | Sequence 4(B-A-C) | Sequence 5(C-A-B) | Sequence 6(C-B-A) |
|---|---|---|---|---|---|---|
| Arm/Group Description | QVM149 150/50/80 μg o.d; QVM149 150/50/160 μg o.d; salmeterol/fluticasone FDC 50/500 μg b.i.d. | QVM149 150/50/80 μg o.d; salmeterol/fluticasone FDC 50/500 μg b.i.d.; QVM149 150/50/160 μg o.d; | QVM149 150/50/160 μg o.d; salmeterol/fluticasone FDC 50/500 μg b.i.d.; QVM149 150/50/80 μg o.d | QVM149 150/50/160 μg o.d; QVM149 150/50/80 μg o.d; salmeterol/fluticasone FDC 50/500 μg b.i.d | salmeterol/fluticasone FDC 50/500 μg b.i.d; QVM149 150/50/80 μg o.d; QVM149 150/50/160 μg o.d | salmeterol/fluticasone FDC 50/500 μg b.i.d.; QVM149 150/50/160 μg o.d; QVM149 150/50/80 μg o.d |
| Period Title: Overall Study | ||||||
| STARTED | 19 | 20 | 18 | 20 | 20 | 19 |
| COMPLETED | 16 | 19 | 17 | 17 | 20 | 18 |
| NOT COMPLETED | 3 | 1 | 1 | 3 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | All participants randomized to one of six treatment sequences |
| Overall Participants | 116 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
49.5
(14)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
55
47.4%
|
| Male |
61
52.6%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
9
7.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
0.9%
|
| White |
106
91.4%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | Salmeterol/Fluticasone 50/500 µg b.i.d |
|---|---|---|---|
| Arm/Group Description | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | salmeterol/fluticasone 50/500 µg b.i.d |
| Measure Participants | 112 | 115 | 111 |
| Least Squares Mean (Standard Error) [Liters] |
2.792
(0.0750)
|
2.779
(0.0750)
|
2.620
(0.0750)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QVM149 150/50/160 μg o.d. |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.172 | |
| Confidence Interval |
(2-Sided) 95% 0.137 to 0.208 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | QVM149 150/50/80 μg o.d. |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | 0.159 | |
| Confidence Interval |
(2-Sided) 95% 0.123 to 0.195 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | Salmeterol/Fluticasone 50/500 µg b.i.d |
|---|---|---|---|
| Arm/Group Description | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | salmeterol/fluticasone 50/500 µg b.i.d |
| Measure Participants | 112 | 115 | 111 |
| -45 min |
2.6237
(0.07505)
|
2.5639
(0.07503)
|
2.4931
(0.07505)
|
| -15 min |
2.6023
(0.07479)
|
2.5630
(0.07478)
|
2.4835
(0.07480)
|
| 5 min |
2.6412
(0.07446)
|
2.6179
(0.07445)
|
2.5035
(0.07446)
|
| 15 min |
2.6696
(0.07531)
|
2.6137
(0.07532)
|
2.5172
(0.07533)
|
| 30 min |
2.6873
(0.07444)
|
2.6504
(0.07444)
|
2.5286
(0.07444)
|
| 1 h |
2.6922
(0.07430)
|
2.6825
(0.07431)
|
2.5398
(0.07431)
|
| 2 h |
2.7033
(0.07441)
|
2.6996
(0.07443)
|
2.5244
(0.07443)
|
| 3 h |
2.6995
(0.07449)
|
2.6719
(0.07450)
|
2.5296
(0.07451)
|
| 4 h |
2.6815
(0.07482)
|
2.6565
(0.07484)
|
2.5164
(0.07485)
|
| 8 h |
2.6801
(0.07454)
|
2.6550
(0.07459)
|
2.4918
(0.07459)
|
| 10 h |
2.6999
(0.07489)
|
2.6796
(0.07494)
|
2.4908
(0.07495)
|
| 11h 55 min |
2.7042
(0.07486)
|
2.6641
(0.07490)
|
2.4841
(0.07491)
|
| 14 h |
2.6829
(0.07456)
|
2.6541
(0.07459)
|
2.5354
(0.07461)
|
| 18 h |
2.6345
(0.07451)
|
2.6073
(0.07455)
|
2.5329
(0.07457)
|
| 21 h |
2.6113
(0.07466)
|
2.5989
(0.07472)
|
2.5133
(0.07475)
|
| 23 h 15 min |
2.6143
(0.07433)
|
2.5950
(0.07438)
|
2.4854
(0.07439)
|
| 23 h 45 min |
2.5966
(0.07433)
|
2.5722
(0.07438)
|
2.4913
(0.07439)
|
| Title | FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | Salmeterol/Fluticasone 50/500 μg b.i.d |
|---|---|---|---|
| Arm/Group Description | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | Salmeterol/fluticasone 50/500 μg b.i.d |
| Measure Participants | 112 | 115 | 111 |
| -45min |
3.9046
(1.03169)
|
3.8538
(0.98086)
|
3.7626
(1.00067)
|
| -15min |
3.8743
(1.04318)
|
3.8571
(0.97420)
|
3.7230
(0.94180)
|
| 5min |
3.8656
(0.99877)
|
3.8976
(1.00323)
|
3.7536
(0.93696)
|
| 15min |
3.8669
(0.98489)
|
3.8971
(0.96840)
|
3.7290
(0.94033)
|
| 30min |
3.8700
(0.99289)
|
3.9002
(0.99091)
|
3.7695
(0.96026)
|
| 1h |
3.8756
(0.99978)
|
3.8993
(0.99141)
|
3.7530
(0.97083)
|
| 2h |
3.8698
(0.99623)
|
3.8985
(0.99369)
|
3.7629
(0.97164)
|
| 3h |
3.8576
(0.98598)
|
3.8766
(0.97806)
|
3.7575
(0.96899)
|
| 4h |
3.8744
(0.99833)
|
3.8627
(0.95673)
|
3.7629
(0.98205)
|
| 8h |
3.9020
(0.98241)
|
3.9217
(0.99184)
|
3.7683
(1.00410)
|
| 10h |
3.8976
(0.98360)
|
3.9504
(0.99286)
|
3.7809
(0.98213)
|
| 11h 55min |
3.9271
(0.98924)
|
3.9405
(1.00198)
|
3.7911
(0.99102)
|
| 14h |
3.9091
(1.00241)
|
3.9210
(0.97942)
|
3.8089
(1.02918)
|
| 18h |
3.8675
(0.95725)
|
3.9151
(1.02198)
|
3.7824
(0.98395)
|
| 21h |
3.8438
(1.00672)
|
3.8694
(0.98786)
|
3.7680
(1.00768)
|
| 23h 15min |
3.7997
(0.97550)
|
3.8673
(0.99915)
|
3.7395
(1.01764)
|
| 23h 45min |
3.8034
(0.99036)
|
3.8603
(0.98502)
|
3.7431
(1.00668)
|
| Title | FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | Salmeterol/Fluticasone 50/500 μg b.i.d |
|---|---|---|---|
| Arm/Group Description | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | Salmeterol/fluticasone 50/500 μg b.i.d |
| Measure Participants | 112 | 115 | 111 |
| -45min |
0.6701
(0.10880)
|
0.6612
(0.10358)
|
0.6527
(0.10867)
|
| -15min |
0.6707
(0.10646)
|
0.6669
(0.10422)
|
0.6539
(0.10526)
|
| 5min |
0.6788
(0.10300)
|
0.6754
(0.10370)
|
0.6563
(0.10639)
|
| 15min |
0.6873
(0.10126)
|
0.6778
(0.10734)
|
0.6560
(0.10823)
|
| 30min |
0.6878
(0.10137)
|
0.6844
(0.10699)
|
0.6573
(0.10552)
|
| 1h |
0.6900
(0.09764)
|
0.6895
(0.09940)
|
0.6632
(0.10403)
|
| 2h |
0.6939
(0.09629)
|
0.6932
(0.10073)
|
0.6647
(0.10413)
|
| 3h |
0.6968
(0.10159)
|
0.6890
(0.10052)
|
0.6634
(0.10436)
|
| 4h |
0.6897
(0.10060)
|
0.6879
(0.09733)
|
0.6605
(0.10419)
|
| 8h |
0.6842
(0.10782)
|
0.6802
(0.11349)
|
0.6492
(0.10814)
|
| 10h |
0.6916
(0.10550)
|
0.6858
(0.10468)
|
0.6489
(0.11155)
|
| 11h 55min |
0.6853
(0.10672)
|
0.6791
(0.10656)
|
0.6482
(0.10810)
|
| 14h |
0.6846
(0.10842)
|
0.6848
(0.10450)
|
0.6567
(0.11048)
|
| 18h |
0.6801
(0.09943)
|
0.6741
(0.10240)
|
0.6546
(0.10369)
|
| 21h |
0.6790
(0.10890)
|
0.6785
(0.10387)
|
0.6562
(0.10729)
|
| 23h 15min |
06821
(0.10386)
|
0.6791
(0.09986)
|
0.6548
(0.10423)
|
| 23h 45min |
0.6782
(0.10457)
|
0.6776
(0.10111)
|
0.6537
(0.10934)
|
| Title | 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) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | Salmeterol/Fluticasone 50/500 µg b.i.d |
|---|---|---|---|
| Arm/Group Description | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | salmeterol/fluticasone 50/500 µg b.i.d |
| Measure Participants | 112 | 115 | 111 |
| FEV1 AUC 5 min - 1 h |
2.673
(0.0735)
|
2.644
(0.0736)
|
2.513
(0.0737)
|
| FEV1 AUC 5 min - 4 h |
2.687
(0.0741)
|
2.669
(0.0741)
|
2.510
(0.0742)
|
| FEV1 AUC 5 min - 23 h 45 min |
2.677
(0.0766)
|
2.652
(0.0768)
|
2.515
(0.0768)
|
| Title | Trough FEV1 After 21 Days of Treatment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | Salmeterol/Fluticasone 50/500 µg b.i.d |
|---|---|---|---|
| Arm/Group Description | QVM149 150/50/160 μg o.d. | QVM149 150/50/80 μg o.d. | salmeterol/fluticasone 50/500 µg b.i.d |
| Measure Participants | 112 | 115 | 111 |
| Least Squares Mean (Standard Error) [Liters] |
2.623
(0.0756)
|
2.6046
(0.0757)
|
2.4998
(0.0757)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | QVM149 150/50/160 μg o.d. |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.124 | |
| Confidence Interval |
(2-Sided) 95% 0.086 to 0.161 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Up to 22 days | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | QVM149 150/50/160 µg o.d. | QVM149 150/50/80 µg o.d. | Salmeterol/Fluticasone 50/500 µg b.i.d. | |||
| Arm/Group Description | QVM149 150/50/160 µg o.d. | QVM149 150/50/80 µg o.d. | Salmeterol/fluticasone 50/500 µg b.i.d. | |||
All Cause Mortality |
||||||
| QVM149 150/50/160 µg o.d. | QVM149 150/50/80 µg o.d. | Salmeterol/Fluticasone 50/500 µg b.i.d. | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/112 (0%) | 0/115 (0%) | 0/111 (0%) | |||
Serious Adverse Events |
||||||
| QVM149 150/50/160 µg o.d. | QVM149 150/50/80 µg o.d. | Salmeterol/Fluticasone 50/500 µg b.i.d. | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/112 (0%) | 0/115 (0%) | 0/111 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| QVM149 150/50/160 µg o.d. | QVM149 150/50/80 µg o.d. | Salmeterol/Fluticasone 50/500 µg b.i.d. | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/112 (12.5%) | 18/115 (15.7%) | 21/111 (18.9%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 3/112 (2.7%) | 7/115 (6.1%) | 4/111 (3.6%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/112 (0%) | 0/115 (0%) | 1/111 (0.9%) | |||
| Nervous system disorders | ||||||
| Headache | 10/112 (8.9%) | 10/115 (8.7%) | 13/111 (11.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dysphonia | 6/112 (5.4%) | 1/115 (0.9%) | 6/111 (5.4%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
- CQVM149B2208