Trial Outcomes & Findings for Roflumilast Plus Montelukast in Adults With Severe Asthma (NCT NCT01765192)
NCT ID: NCT01765192
Last Updated: 2017-02-01
Results Overview
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 will be measured using spirometry in accordance with the American Thoracic Society / European Respiratory Society (ATS/ERS) consensus guidelines. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline FEV1 measurement as the covariate was used for analysis.
COMPLETED
PHASE2
64 participants
Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)
2017-02-01
Participant Flow
Participants took part in the study at 12 investigative sites in Germany, Hungary, and South Africa from 15 February 2013 to 24 October 2013.
Participants with a historical diagnosis of severe asthma who were inadequately controlled while receiving a combination of at least medium dose inhaled corticosteroids and long-acting beta agonists maintenance therapy were enrolled in 1 of 2 treatment sequences, 500 µg roflumilast plus 10 mg montelukast once daily (QD) or 10 mg montelukast QD.
Participant milestones
| Measure |
Placebo Plus Montelukast, Then Roflumilast Plus Montelukast
Participants in sequence 2 received placebo plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Roflumilast Plus Montelukast, Then Placebo Plus Montelukast
Participants in sequence 1 received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
32
|
32
|
|
Treatment Period 1
COMPLETED
|
31
|
32
|
|
Treatment Period 1
NOT COMPLETED
|
1
|
0
|
|
Washout Period
STARTED
|
31
|
32
|
|
Washout Period
COMPLETED
|
30
|
30
|
|
Washout Period
NOT COMPLETED
|
1
|
2
|
|
Treatment Period 2
STARTED
|
30
|
30
|
|
Treatment Period 2
COMPLETED
|
28
|
30
|
|
Treatment Period 2
NOT COMPLETED
|
2
|
0
|
|
End of Treatment Period 2 to Final Visit
STARTED
|
28
|
30
|
|
End of Treatment Period 2 to Final Visit
COMPLETED
|
27
|
30
|
|
End of Treatment Period 2 to Final Visit
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Placebo Plus Montelukast, Then Roflumilast Plus Montelukast
Participants in sequence 2 received placebo plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Roflumilast Plus Montelukast, Then Placebo Plus Montelukast
Participants in sequence 1 received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Treatment Period 1
Adverse Event
|
1
|
0
|
|
Washout Period
Voluntary Withdrawal
|
1
|
1
|
|
Washout Period
Reason not specified
|
0
|
1
|
|
Treatment Period 2
Reason not specified
|
2
|
0
|
|
End of Treatment Period 2 to Final Visit
Adverse Event
|
1
|
0
|
Baseline Characteristics
Roflumilast Plus Montelukast in Adults With Severe Asthma
Baseline characteristics by cohort
| Measure |
Roflumilast Plus Montelukast, Then Placebo Plus Montelukast
n=32 Participants
Participants in sequence 1 received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast, Then Roflumilast Plus Montelukast
n=32 Participants
Participants in sequence 2 received placebo plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Total
n=64 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.3 years
STANDARD_DEVIATION 13.80 • n=93 Participants
|
50.0 years
STANDARD_DEVIATION 14.10 • n=4 Participants
|
50.1 years
STANDARD_DEVIATION 13.84 • n=27 Participants
|
|
Age, Customized
< 65 years
|
27 participants
n=93 Participants
|
27 participants
n=4 Participants
|
54 participants
n=27 Participants
|
|
Age, Customized
≥ 65 years
|
5 participants
n=93 Participants
|
5 participants
n=4 Participants
|
10 participants
n=27 Participants
|
|
Gender
Female
|
21 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
41 Participants
n=27 Participants
|
|
Gender
Male
|
11 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 participants
n=93 Participants
|
0 participants
n=4 Participants
|
3 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
29 participants
n=93 Participants
|
32 participants
n=4 Participants
|
61 participants
n=27 Participants
|
|
Region of Enrollment
South Africa
|
16 participants
n=93 Participants
|
11 participants
n=4 Participants
|
27 participants
n=27 Participants
|
|
Region of Enrollment
Germany
|
8 participants
n=93 Participants
|
12 participants
n=4 Participants
|
20 participants
n=27 Participants
|
|
Region of Enrollment
Hungary
|
8 participants
n=93 Participants
|
9 participants
n=4 Participants
|
17 participants
n=27 Participants
|
|
Height
|
163.7 cm
STANDARD_DEVIATION 8.47 • n=93 Participants
|
168.3 cm
STANDARD_DEVIATION 10.68 • n=4 Participants
|
166.0 cm
STANDARD_DEVIATION 9.85 • n=27 Participants
|
|
Weight
|
79.06 kg
STANDARD_DEVIATION 18.708 • n=93 Participants
|
85.16 kg
STANDARD_DEVIATION 17.491 • n=4 Participants
|
82.11 kg
STANDARD_DEVIATION 18.227 • n=27 Participants
|
|
Body Mass Index (BMI)
|
29.53 kg/m^2
STANDARD_DEVIATION 7.105 • n=93 Participants
|
30.06 kg/m^2
STANDARD_DEVIATION 5.605 • n=4 Participants
|
29.79 kg/m^2
STANDARD_DEVIATION 6.354 • n=27 Participants
|
|
Smoking History
Never smoked
|
22 participants
n=93 Participants
|
21 participants
n=4 Participants
|
43 participants
n=27 Participants
|
|
Smoking History
Current smoker
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
|
Smoking History
Ex-smoker
|
10 participants
n=93 Participants
|
11 participants
n=4 Participants
|
21 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)Population: Full analysis set: All randomized participants, analyzed according to the randomized treatment with FEV1 data available for analysis after 4 weeks of treatment.
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 will be measured using spirometry in accordance with the American Thoracic Society / European Respiratory Society (ATS/ERS) consensus guidelines. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline FEV1 measurement as the covariate was used for analysis.
Outcome measures
| Measure |
Roflumilast Plus Montelukast
n=58 Participants
Participants received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast
n=61 Participants
Participants received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
|
0.18 liters
Standard Error 0.028
|
0.08 liters
Standard Error 0.027
|
SECONDARY outcome
Timeframe: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)Population: Full analysis set: All randomized participants, analyzed according to the randomized treatment with FVC data available for analysis after 4 weeks of treatment.
FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be measured using spirometry in accordance with ATS/ERS consensus guidelines. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline FVC measurement as the covariate was used for analysis.
Outcome measures
| Measure |
Roflumilast Plus Montelukast
n=58 Participants
Participants received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast
n=61 Participants
Participants received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Vital Capacity (FVC)
|
0.12 liters
Standard Error 0.029
|
0.06 liters
Standard Error 0.027
|
SECONDARY outcome
Timeframe: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)Population: Full analysis set: All randomized participants, analyzed according to the randomized treatment with FEF data available for analysis after 4 weeks of treatment.
FEF is a measure of how much air can be exhaled from the lungs. It is an indicator of obstruction of the smaller airways. FEF25-75% is the mid-flow rate or forced expiratory flow occurring in the middle 50% of the patient's exhaled volume, and will be measured using spirometry in accordance with ATS/ERS consensus guidelines. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline FEF measurement as the covariate was used for analysis.
Outcome measures
| Measure |
Roflumilast Plus Montelukast
n=54 Participants
Participants received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast
n=55 Participants
Participants received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Forced Expiratory Flow (FEF) 25-75%
|
0.23 liters/second
Standard Error 0.039
|
0.11 liters/second
Standard Error 0.039
|
SECONDARY outcome
Timeframe: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)Population: Full analysis set: All randomized participants, analyzed according to the randomized treatment with PEF data available for analysis after 4 weeks of treatment.
PEF is a person's maximum speed of expiration. It measures the airflow through the bronchi and thus the degree of obstruction in the airways. PEF will be measured using spirometry in accordance with ATS/ERS consensus guidelines. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline PEF measurement as the covariate was used for analysis.
Outcome measures
| Measure |
Roflumilast Plus Montelukast
n=58 Participants
Participants received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast
n=61 Participants
Participants received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Pre-Dose (Trough) Pre-Bronchodilator Peak Expiratory Flow (PEF)
|
15.05 liters/minute (L/min)
Standard Error 10.616
|
7.85 liters/minute (L/min)
Standard Error 10.401
|
SECONDARY outcome
Timeframe: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)Population: Full analysis set: All randomized participants, analyzed according to the randomized treatment with PEF data available for analysis after 4 weeks of treatment.
PEF will be measured at home using portable electronic peak flow meter. The participant will record PEF daily in the morning immediately after getting up. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline PEF measurement as the covariate was used for analysis.
Outcome measures
| Measure |
Roflumilast Plus Montelukast
n=60 Participants
Participants received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast
n=61 Participants
Participants received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Morning Peak Expiratory Flow (PEF)
|
20.85 L/min
Standard Error 3.708
|
7.23 L/min
Standard Error 3.646
|
SECONDARY outcome
Timeframe: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)Population: Full analysis set: All randomized participants, analyzed according to the randomized treatment with data available for analysis after 4 weeks of treatment.
Patients will assess their daily day-time asthma symptoms according to the following scale: 0: Very well, no symptoms. 1: One episode of wheezing, cough or breathlessness. 2: More than one episode of wheezing, cough or breathlessness without interfering with normal activities. 3: Wheezing, cough or short of breath most of the day which interfered to some extent with normal activities. 4: Asthma very bad. Unable to carry out daily activities as usual. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline Daytime Asthma Symptoms measurement as the covariate was used for analysis. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Roflumilast Plus Montelukast
n=60 Participants
Participants received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast
n=61 Participants
Participants received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Daytime Asthma Symptoms
|
-0.39 units on a scale
Standard Error 0.061
|
-0.18 units on a scale
Standard Error 0.063
|
SECONDARY outcome
Timeframe: Baseline (Days 1 and 56) and after 4 weeks of treatment (Days 28 and 84)Population: Full analysis set: All randomized participants, analyzed according to the randomized treatment with data available for analysis after 4 weeks of treatment.
Patients will assess their daily night-time asthma symptoms according to the following scale: 0: No symptoms, slept through the night. 1: Slept well but some complaints in the morning. 2: Woke up once because of asthma (inclusive early awakening). 3: Woke up several times because of asthma (inclusive early awakening). 4: Bad night, awake most of the night because of asthma. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline Nighttime Asthma Symptoms measurement as the covariate was used for analysis. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Roflumilast Plus Montelukast
n=60 Participants
Participants received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast
n=61 Participants
Participants received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Nighttime Asthma Symptoms
|
-0.27 units on a scale
Standard Error 0.053
|
-0.17 units on a scale
Standard Error 0.052
|
Adverse Events
Roflumilast Plus Montelukast
Placebo Plus Montelukast
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Roflumilast Plus Montelukast
n=61 participants at risk
Participants received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks.
|
Placebo Plus Montelukast
n=62 participants at risk
Participants received placebo plus montelukast 10 mg orally once daily for 4 weeks.
|
|---|---|---|
|
Nervous system disorders
Headache
|
8.2%
5/61 • Baseline to the end of the study (Days 1-105)
Safety analysis set: All randomized participants who received at least 1 dose of study drug. Adverse events are reported for 61 and 62 participants in the roflumilast + montelukast (R+M) and placebo + montelukast (P+M) groups, respectively, as 3 participants discontinued prior to receiving R+M and 2 participants discontinued prior to receiving P+M.
|
0.00%
0/62 • Baseline to the end of the study (Days 1-105)
Safety analysis set: All randomized participants who received at least 1 dose of study drug. Adverse events are reported for 61 and 62 participants in the roflumilast + montelukast (R+M) and placebo + montelukast (P+M) groups, respectively, as 3 participants discontinued prior to receiving R+M and 2 participants discontinued prior to receiving P+M.
|
Additional Information
AstraZeneca Clinical Study Information Center
AstraZeneca
Results disclosure agreements
- Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER