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Assess Bronchodilator Effect and Safety of Two Doses of QVM149 Compared to a Fixed Dose Combination of Salmeterol/Fluticasone in Patients With Asthma.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03063086
Recruitment Status : Completed
First Posted : February 24, 2017
Results First Posted : December 13, 2019
Last Update Posted : December 13, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: QVM149 150/50/80 μg o.d.
Drug: QVM149 150/50/160 μg o.d.
Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.
Enrollment 116
Recruitment Details  
Pre-assignment Details  
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)
Hide 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
Reason Not Completed
technical problems             1             0             0             0             0             0
Adverse Event             1             1             1             1             0             0
subject/guardian decision             1             0             0             0             0             0
Non-compliance with study treatment             0             0             0             1             0             1
Physician Decision             0             0             0             1             0             0
Arm/Group Title All Participants
Hide Arm/Group Description All participants randomized to one of six treatment sequences
Overall Number of Baseline Participants 116
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 116 participants
49.5  (14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants
Female
55
  47.4%
Male
61
  52.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants
American Indian or Alaska Native
0
   0.0%
Asian
9
   7.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   0.9%
White
106
  91.4%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 112 115 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
2.792  (0.0750) 2.779  (0.0750) 2.620  (0.0750)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVM149 150/50/160 μg o.d.
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.172
Confidence Interval (2-Sided) 95%
0.137 to 0.208
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QVM149 150/50/80 μg o.d.
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.159
Confidence Interval (2-Sided) 95%
0.123 to 0.195
Estimation Comments [Not Specified]
2.Secondary Outcome
Title FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose
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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 112 115 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-45 min Number Analyzed 111 participants 111 participants 111 participants
2.6237  (0.07505) 2.5639  (0.07503) 2.4931  (0.07505)
-15 min Number Analyzed 111 participants 109 participants 109 participants
2.6023  (0.07479) 2.5630  (0.07478) 2.4835  (0.07480)
5 min Number Analyzed 110 participants 108 participants 109 participants
2.6412  (0.07446) 2.6179  (0.07445) 2.5035  (0.07446)
15 min Number Analyzed 110 participants 108 participants 108 participants
2.6696  (0.07531) 2.6137  (0.07532) 2.5172  (0.07533)
30 min Number Analyzed 110 participants 108 participants 110 participants
2.6873  (0.07444) 2.6504  (0.07444) 2.5286  (0.07444)
1 h Number Analyzed 110 participants 107 participants 108 participants
2.6922  (0.07430) 2.6825  (0.07431) 2.5398  (0.07431)
2 h Number Analyzed 109 participants 107 participants 107 participants
2.7033  (0.07441) 2.6996  (0.07443) 2.5244  (0.07443)
3 h Number Analyzed 109 participants 107 participants 106 participants
2.6995  (0.07449) 2.6719  (0.07450) 2.5296  (0.07451)
4 h Number Analyzed 109 participants 107 participants 106 participants
2.6815  (0.07482) 2.6565  (0.07484) 2.5164  (0.07485)
8 h Number Analyzed 109 participants 104 participants 105 participants
2.6801  (0.07454) 2.6550  (0.07459) 2.4918  (0.07459)
10 h Number Analyzed 108 participants 105 participants 105 participants
2.6999  (0.07489) 2.6796  (0.07494) 2.4908  (0.07495)
11h 55 min Number Analyzed 107 participants 104 participants 103 participants
2.7042  (0.07486) 2.6641  (0.07490) 2.4841  (0.07491)
14 h Number Analyzed 107 participants 103 participants 103 participants
2.6829  (0.07456) 2.6541  (0.07459) 2.5354  (0.07461)
18 h Number Analyzed 107 participants 102 participants 102 participants
2.6345  (0.07451) 2.6073  (0.07455) 2.5329  (0.07457)
21 h Number Analyzed 107 participants 102 participants 100 participants
2.6113  (0.07466) 2.5989  (0.07472) 2.5133  (0.07475)
23 h 15 min Number Analyzed 105 participants 100 participants 100 participants
2.6143  (0.07433) 2.5950  (0.07438) 2.4854  (0.07439)
23 h 45 min Number Analyzed 105 participants 99 participants 100 participants
2.5966  (0.07433) 2.5722  (0.07438) 2.4913  (0.07439)
3.Secondary Outcome
Title FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose
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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 112 115 111
Mean (Standard Deviation)
Unit of Measure: Liters
-45min Number Analyzed 111 participants 110 participants 110 participants
3.9046  (1.03169) 3.8538  (0.98086) 3.7626  (1.00067)
-15min Number Analyzed 111 participants 109 participants 108 participants
3.8743  (1.04318) 3.8571  (0.97420) 3.7230  (0.94180)
5min Number Analyzed 110 participants 107 participants 107 participants
3.8656  (0.99877) 3.8976  (1.00323) 3.7536  (0.93696)
15min Number Analyzed 110 participants 107 participants 106 participants
3.8669  (0.98489) 3.8971  (0.96840) 3.7290  (0.94033)
30min Number Analyzed 109 participants 108 participants 108 participants
3.8700  (0.99289) 3.9002  (0.99091) 3.7695  (0.96026)
1h Number Analyzed 109 participants 107 participants 107 participants
3.8756  (0.99978) 3.8993  (0.99141) 3.7530  (0.97083)
2h Number Analyzed 108 participants 107 participants 107 participants
3.8698  (0.99623) 3.8985  (0.99369) 3.7629  (0.97164)
3h Number Analyzed 109 participants 106 participants 105 participants
3.8576  (0.98598) 3.8766  (0.97806) 3.7575  (0.96899)
4h Number Analyzed 109 participants 107 participants 106 participants
3.8744  (0.99833) 3.8627  (0.95673) 3.7629  (0.98205)
8h Number Analyzed 109 participants 103 participants 105 participants
3.9020  (0.98241) 3.9217  (0.99184) 3.7683  (1.00410)
10h Number Analyzed 108 participants 103 participants 105 participants
3.8976  (0.98360) 3.9504  (0.99286) 3.7809  (0.98213)
11h 55min Number Analyzed 107 participants 102 participants 102 participants
3.9271  (0.98924) 3.9405  (1.00198) 3.7911  (0.99102)
14h Number Analyzed 107 participants 103 participants 103 participants
3.9091  (1.00241) 3.9210  (0.97942) 3.8089  (1.02918)
18h Number Analyzed 107 participants 102 participants 101 participants
3.8675  (0.95725) 3.9151  (1.02198) 3.7824  (0.98395)
21h Number Analyzed 107 participants 101 participants 100 participants
3.8438  (1.00672) 3.8694  (0.98786) 3.7680  (1.00768)
23h 15min Number Analyzed 104 participants 100 participants 100 participants
3.7997  (0.97550) 3.8673  (0.99915) 3.7395  (1.01764)
23h 45min Number Analyzed 105 participants 99 participants 98 participants
3.8034  (0.99036) 3.8603  (0.98502) 3.7431  (1.00668)
4.Secondary Outcome
Title FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose
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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 112 115 111
Mean (Standard Deviation)
Unit of Measure: Ratio
-45min Number Analyzed 107 participants 107 participants 108 participants
0.6701  (0.10880) 0.6612  (0.10358) 0.6527  (0.10867)
-15min Number Analyzed 107 participants 106 participants 108 participants
0.6707  (0.10646) 0.6669  (0.10422) 0.6539  (0.10526)
5min Number Analyzed 109 participants 106 participants 103 participants
0.6788  (0.10300) 0.6754  (0.10370) 0.6563  (0.10639)
15min Number Analyzed 106 participants 103 participants 103 participants
0.6873  (0.10126) 0.6778  (0.10734) 0.6560  (0.10823)
30min Number Analyzed 106 participants 103 participants 108 participants
0.6878  (0.10137) 0.6844  (0.10699) 0.6573  (0.10552)
1h Number Analyzed 108 participants 106 participants 105 participants
0.6900  (0.09764) 0.6895  (0.09940) 0.6632  (0.10403)
2h Number Analyzed 107 participants 105 participants 106 participants
0.6939  (0.09629) 0.6932  (0.10073) 0.6647  (0.10413)
3h Number Analyzed 108 participants 106 participants 104 participants
0.6968  (0.10159) 0.6890  (0.10052) 0.6634  (0.10436)
4h Number Analyzed 106 participants 107 participants 105 participants
0.6897  (0.10060) 0.6879  (0.09733) 0.6605  (0.10419)
8h Number Analyzed 105 participants 95 participants 102 participants
0.6842  (0.10782) 0.6802  (0.11349) 0.6492  (0.10814)
10h Number Analyzed 105 participants 99 participants 104 participants
0.6916  (0.10550) 0.6858  (0.10468) 0.6489  (0.11155)
11h 55min Number Analyzed 103 participants 99 participants 102 participants
0.6853  (0.10672) 0.6791  (0.10656) 0.6482  (0.10810)
14h Number Analyzed 104 participants 101 participants 101 participants
0.6846  (0.10842) 0.6848  (0.10450) 0.6567  (0.11048)
18h Number Analyzed 104 participants 101 participants 97 participants
0.6801  (0.09943) 0.6741  (0.10240) 0.6546  (0.10369)
21h Number Analyzed 106 participants 99 participants 99 participants
0.6790  (0.10890) 0.6785  (0.10387) 0.6562  (0.10729)
23h 15min Number Analyzed 102 participants 98 participants 100 participants
06821  (0.10386) 0.6791  (0.09986) 0.6548  (0.10423)
23h 45min Number Analyzed 104 participants 98 participants 98 participants
0.6782  (0.10457) 0.6776  (0.10111) 0.6537  (0.10934)
5.Secondary Outcome
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)
Time Frame 3 weeks
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 112 115 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
FEV1 AUC 5 min - 1 h Number Analyzed 108 participants 103 participants 100 participants
2.673  (0.0735) 2.644  (0.0736) 2.513  (0.0737)
FEV1 AUC 5 min - 4 h Number Analyzed 104 participants 104 participants 99 participants
2.687  (0.0741) 2.669  (0.0741) 2.510  (0.0742)
FEV1 AUC 5 min - 23 h 45 min Number Analyzed 101 participants 93 participants 92 participants
2.677  (0.0766) 2.652  (0.0768) 2.515  (0.0768)
6.Secondary Outcome
Title Trough FEV1 After 21 Days of Treatment
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 112 115 111
Least Squares Mean (Standard Error)
Unit of Measure: Liters
2.623  (0.0756) 2.6046  (0.0757) 2.4998  (0.0757)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVM149 150/50/160 μg o.d.
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.124
Confidence Interval (2-Sided) 95%
0.086 to 0.161
Estimation Comments [Not Specified]
Time Frame Up to 22 days
Adverse Event Reporting Description [Not Specified]
 
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.
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/112 (0.00%)   0/115 (0.00%)   0/111 (0.00%) 
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/112 (0.00%)   0/115 (0.00%)   0/111 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/112 (12.50%)   18/115 (15.65%)   21/111 (18.92%) 
Infections and infestations       
Nasopharyngitis  1  3/112 (2.68%)  7/115 (6.09%)  4/111 (3.60%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  0/112 (0.00%)  0/115 (0.00%)  1/111 (0.90%) 
Nervous system disorders       
Headache  1  10/112 (8.93%)  10/115 (8.70%)  13/111 (11.71%) 
Respiratory, thoracic and mediastinal disorders       
Dysphonia  1  6/112 (5.36%)  1/115 (0.87%)  6/111 (5.41%) 
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT03063086    
Other Study ID Numbers: CQVM149B2208
First Submitted: February 21, 2017
First Posted: February 24, 2017
Results First Submitted: July 31, 2019
Results First Posted: December 13, 2019
Last Update Posted: December 13, 2019