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Assess Bronchodilator Effect QVM149 Dosed Either in the Morning or Evening Compared to Placebo in Patients With Asthma (QVM149)

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: NCT03108027
Recruitment Status : Completed
First Posted : April 11, 2017
Results First Posted : May 21, 2019
Last Update Posted : May 21, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)
Enrollment 38
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4 Sequence 5 Sequence 6
Hide Arm/Group Description Patients received in a sequential order the following interventional treatments: A,B and C. Patients received in a sequential order the following interventional treatments: B, A and C. Patients received in a sequential order the following interventional treatments: C, B and A. Patients received in a sequential order the following interventional treatments : C, A and B. Patients received in a sequential order the following interventional treatments: A, C and B. Patients received in a sequential order the following interventional treatments: B, C and A.
Period Title: Period 1
Started 7 6 6 6 6 6
Completed 7 6 6 4 6 6
Not Completed 0 0 0 2 0 0
Reason Not Completed
Subject/Guardian Decision             0             0             0             2             0             0
Period Title: Period 2
Started 7 6 6 4 6 6
Completed 7 6 6 4 6 6
Not Completed 0 0 0 0 0 0
Period Title: Period 3
Started 7 6 6 4 6 6
Completed 7 5 6 4 6 6
Not Completed 0 1 0 0 0 0
Reason Not Completed
Adverse Event             0             1             0             0             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 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants
43.5  (14.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
16
  43.2%
Male
21
  56.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
35
  94.6%
More than one race
0
   0.0%
Unknown or Not Reported
2
   5.4%
1.Primary Outcome
Title FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period
Hide Description Weighted mean forced expiratory volume in 1 second (FEV1) over 24 h (AUC0-24h) following 14 days of treatment with QVM149 dosed in the morning, QVM149 dosed in the evening and placebo.
Time Frame At the end of each treatment period day 14 pre-dose to 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacodynamic (PD) analysis set included all patients with any available PD data, who received any dose of study drug and experienced no protocol deviations with relevant impact on PD data.
Arm/Group Title QVM149 am QVM149 pm Placebo
Hide Arm/Group Description:
QVM149 150/50/80 μg o.d. (indacaterol acetate 150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the morning (plus matching placebo in the evening)
QVM149 150/50/80 μg o.d. (indacaterol acetate150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the evening (plus matching placebo in the morning)
Placebo administered in the morning and in the evening.
Overall Number of Participants Analyzed 30 30 33
Least Squares Mean (Standard Error)
Unit of Measure: Liters
3.4305  (0.15242) 3.4361  (0.15213) 2.8209  (0.15259)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVM149 am, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.6096
Confidence Interval (2-Sided) 90%
0.5380 to 0.6811
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QVM149 pm, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.6152
Confidence Interval (2-Sided) 90%
0.5437 to 0.6868
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection QVM149 am, QVM149 pm
Comments [Not Specified]
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0057
Confidence Interval (2-Sided) 90%
-0.0760 to 0.0647
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Trough FEV1 After 24h
Hide Description FEV1 at approximately 24 h after the last p.m. or penultimate a.m. dose. Morning and evening trough FEV1 (L) were analyzed by time of day. For morning trough FEV1 (L) assessments this meant that the spirometric assessment was done approximately 24 h after last morning dose and approximately 12 h after last evening dose.
Time Frame At the end of each treatment period day 14 pre-dose to 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacodynamic (PD) analysis set included all patients with any available PD data, who received any dose of study drug and experienced no protocol deviations with relevant impact on PD data
Arm/Group Title QVM149 am QVM149 pm Placebo
Hide Arm/Group Description:
QVM149 150/50/80 μg o.d. (indacaterol acetate 150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the morning (plus matching placebo in the evening)
QVM149 150/50/80 μg o.d. (indacaterol acetate150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the evening (plus matching placebo in the morning)
Placebo administered in the morning and in the evening.
Overall Number of Participants Analyzed 35 35 36
Least Squares Mean (Standard Error)
Unit of Measure: Liters
3.3731  (0.15037) 3.4871  (0.15041) 2.7524  (0.15120)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVM149 am, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.6206
Confidence Interval (2-Sided) 90%
0.5335 to 0.7077
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QVM149 pm, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.7347
Confidence Interval (2-Sided) 90%
0.6469 to 0.8225
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection QVM149 am, QVM149 pm
Comments [Not Specified]
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1141
Confidence Interval (2-Sided) 90%
-0.1970 to -0.0311
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Peak Expiratory Flow (PEF)
Hide Description Peak expiratory flow (PEF) is the maximum flow generated during a forceful exhalation, starting from full lung inflationDaily morning and evening peak expiratory flow rate from Day 2 to Day14 during the three treatment periods.
Time Frame From treatment period start through study completion (up to 19 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacodynamic (PD) analysis set included all patients with any available PD data, who received any dose of study drug and experienced no protocol deviations with relevant impact on PD data
Arm/Group Title QVM149 am QVM149 pm Placebo
Hide Arm/Group Description:
QVM149 150/50/80 μg o.d. (indacaterol acetate 150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the morning (plus matching placebo in the evening)
QVM149 150/50/80 μg o.d. (indacaterol acetate150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the evening (plus matching placebo in the morning)
Placebo administered in the morning and in the evening.
Overall Number of Participants Analyzed 35 35 36
Least Squares Mean (Standard Error)
Unit of Measure: L/min
Morning average PEF 489.6  (19.77) 504.4  (19.78) 417.5  (19.73)
Evening average PEF 522.0  (19.71) 507.7  (19.71) 449.0  (19.67)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVM149 am, Placebo
Comments Morning average PEF
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 72.1
Confidence Interval (2-Sided) 90%
61.3 to 82.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QVM149 pm, Placebo
Comments Morning average PEF
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 86.9
Confidence Interval (2-Sided) 90%
76.1 to 97.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection QVM149 am, QVM149 pm
Comments Morning average PEF
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -14.8
Confidence Interval (2-Sided) 90%
-25.6 to -4.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection QVM149 am, Placebo
Comments Evening average PEF
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 73.1
Confidence Interval (2-Sided) 90%
61.9 to 84.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection QVM149 pm, Placebo
Comments Evening average PEF
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 58.7
Confidence Interval 90%
47.5 to 69.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection QVM149 am, QVM149 pm
Comments Evening average PEF
Type of Statistical Test Other
Comments A hypothesis test is not planned for this study, inferences are to be performed by interpreting confidence interval of treatment difference.’
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 14.4
Confidence Interval (2-Sided) 90%
3.3 to 25.5
Estimation Comments [Not Specified]
Time Frame Up to 19 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title QVM149 a.m. QVM149 p.m. Placebo
Hide Arm/Group Description QVM149 150/50/80 μg o.d. (indacaterol acetate 150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the morning (plus matching placebo in the evening) QVM149 150/50/80 μg o.d. (indacaterol acetate150 μg/ glycopyrronium bromide 50 μg/ MF 80 μg once daily) administered in the evening (plus matching placebo in the morning) Placebo administered in the morning and in the evening
All-Cause Mortality
QVM149 a.m. QVM149 p.m. Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)   0/35 (0.00%)   0/36 (0.00%) 
Hide Serious Adverse Events
QVM149 a.m. QVM149 p.m. Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)   0/35 (0.00%)   0/36 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
QVM149 a.m. QVM149 p.m. Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/35 (31.43%)   13/35 (37.14%)   16/36 (44.44%) 
Infections and infestations       
Nasopharyngitis  1  2/35 (5.71%)  2/35 (5.71%)  5/36 (13.89%) 
Nervous system disorders       
Headache  1  5/35 (14.29%)  3/35 (8.57%)  7/36 (19.44%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/35 (2.86%)  2/35 (5.71%)  1/36 (2.78%) 
Dysphonia  1  2/35 (5.71%)  3/35 (8.57%)  1/36 (2.78%) 
Oropharyngeal pain  1  3/35 (8.57%)  4/35 (11.43%)  2/36 (5.56%) 
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 Pharmaceutical
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT03108027    
Other Study ID Numbers: CQVM149B2209
2017-000644-17 ( EudraCT Number )
First Submitted: March 23, 2017
First Posted: April 11, 2017
Results First Submitted: February 22, 2019
Results First Posted: May 21, 2019
Last Update Posted: May 21, 2019