Trial Outcomes & Findings for Assess Bronchodilator Effect QVM149 Dosed Either in the Morning or Evening Compared to Placebo in Patients With Asthma (NCT NCT03108027)
NCT ID: NCT03108027
Last Updated: 2021-01-05
Results Overview
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.
COMPLETED
PHASE2
38 participants
At the end of each treatment period day 14 pre-dose to 24 hours post-dose.
2021-01-05
Participant Flow
Participant milestones
| Measure |
Sequence 1
Patients received in a sequential order the following interventional treatments: A,B and C.
|
Sequence 2
Patients received in a sequential order the following interventional treatments: B, A and C.
|
Sequence 3
Patients received in a sequential order the following interventional treatments: C, B and A.
|
Sequence 4
Patients received in a sequential order the following interventional treatments : C, A and B.
|
Sequence 5
Patients received in a sequential order the following interventional treatments: A, C and B.
|
Sequence 6
Patients received in a sequential order the following interventional treatments: B, C and A.
|
|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
7
|
6
|
6
|
6
|
6
|
6
|
|
Period 1
COMPLETED
|
7
|
6
|
6
|
4
|
6
|
6
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
2
|
0
|
0
|
|
Period 2
STARTED
|
7
|
6
|
6
|
4
|
6
|
6
|
|
Period 2
COMPLETED
|
7
|
6
|
6
|
4
|
6
|
6
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
7
|
6
|
6
|
4
|
6
|
6
|
|
Period 3
COMPLETED
|
7
|
5
|
6
|
4
|
6
|
6
|
|
Period 3
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
Patients received in a sequential order the following interventional treatments: A,B and C.
|
Sequence 2
Patients received in a sequential order the following interventional treatments: B, A and C.
|
Sequence 3
Patients received in a sequential order the following interventional treatments: C, B and A.
|
Sequence 4
Patients received in a sequential order the following interventional treatments : C, A and B.
|
Sequence 5
Patients received in a sequential order the following interventional treatments: A, C and B.
|
Sequence 6
Patients received in a sequential order the following interventional treatments: B, C and A.
|
|---|---|---|---|---|---|---|
|
Period 1
Subject/Guardian Decision
|
0
|
0
|
0
|
2
|
0
|
0
|
|
Period 3
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Assess Bronchodilator Effect QVM149 Dosed Either in the Morning or Evening Compared to Placebo in Patients With Asthma
Baseline characteristics by cohort
| Measure |
All Participants
n=37 Participants
All participants randomized to one of six treatment sequences
|
|---|---|
|
Age, Continuous
|
43.5 Years
STANDARD_DEVIATION 14.04 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
35 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At the end of each treatment period day 14 pre-dose to 24 hours post-dose.Population: 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.
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.
Outcome measures
| Measure |
QVM149 am
n=30 Participants
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 pm
n=30 Participants
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
n=33 Participants
Placebo administered in the morning and in the evening.
|
|---|---|---|---|
|
FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period
|
3.4305 Liters
Standard Error 0.15242
|
3.4361 Liters
Standard Error 0.15213
|
2.8209 Liters
Standard Error 0.15259
|
SECONDARY outcome
Timeframe: At the end of each treatment period day 14 pre-dose to 24 hours post-dose.Population: 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
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.
Outcome measures
| Measure |
QVM149 am
n=35 Participants
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 pm
n=35 Participants
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
n=36 Participants
Placebo administered in the morning and in the evening.
|
|---|---|---|---|
|
Trough FEV1 After 24h
|
3.3731 Liters
Standard Error 0.15037
|
3.4871 Liters
Standard Error 0.15041
|
2.7524 Liters
Standard Error 0.15120
|
SECONDARY outcome
Timeframe: From treatment period start through study completion (up to 19 weeks).Population: 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
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.
Outcome measures
| Measure |
QVM149 am
n=35 Participants
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 pm
n=35 Participants
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
n=36 Participants
Placebo administered in the morning and in the evening.
|
|---|---|---|---|
|
Peak Expiratory Flow (PEF)
Morning average PEF
|
489.6 L/min
Standard Error 19.77
|
504.4 L/min
Standard Error 19.78
|
417.5 L/min
Standard Error 19.73
|
|
Peak Expiratory Flow (PEF)
Evening average PEF
|
522.0 L/min
Standard Error 19.71
|
507.7 L/min
Standard Error 19.71
|
449.0 L/min
Standard Error 19.67
|
Adverse Events
QVM149 a.m.
QVM149 p.m.
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
QVM149 a.m.
n=35 participants at risk
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 p.m.
n=35 participants at risk
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
n=36 participants at risk
Placebo administered in the morning and in the evening
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.7%
2/35 • Up to 19 weeks
|
5.7%
2/35 • Up to 19 weeks
|
13.9%
5/36 • Up to 19 weeks
|
|
Nervous system disorders
Headache
|
14.3%
5/35 • Up to 19 weeks
|
8.6%
3/35 • Up to 19 weeks
|
19.4%
7/36 • Up to 19 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.9%
1/35 • Up to 19 weeks
|
5.7%
2/35 • Up to 19 weeks
|
2.8%
1/36 • Up to 19 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
5.7%
2/35 • Up to 19 weeks
|
8.6%
3/35 • Up to 19 weeks
|
2.8%
1/36 • Up to 19 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
8.6%
3/35 • Up to 19 weeks
|
11.4%
4/35 • Up to 19 weeks
|
5.6%
2/36 • Up to 19 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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
- Publication restrictions are in place
Restriction type: OTHER