Asthma
Conditions
Brief summary
This is a 6 week study to assess the effect of BI 671800 in patients with asthma. It is a double blind, parallel arm trial testing the safety and efficacy of BI 671800. The main objective is to assess the effect on lung function. The study will also provide data on the pharmacokinetics of BI 671800.
Interventions
DRUGBI 671800
Double blind randomised parallel group study to assess efficacy and tolerability of BI 617800 in patients with symptomatic asthma
DRUGPlacebo
Patients receive placebo capsules and/or encapsulated tablets
DRUGMontelukast
Double blind randomised parallel group study to assess efficacy and tolerability of BI 671800 in patients with symptomatic asthma
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent consistent with ICH-GCP 2. Three month history of reversible (12% and 200 mL in forced expiratory volume in one second - FEV1) asthma (according to GINA) with following spirometry at randomisation: FEV1 60%- 85%. 3. Stable inhaled corticosteroids (iCS) dose 3 months prior to screening. 4. Diagnosis of asthma prior to 40 years. 5. Asthma Control Questionnaire (ACQ) at least 1.5 at randomisation. 6. Male or female 18 to 65 years. 7. Non-smokers or ex-smokers (less than 10 pack years history) with negative cotinine screen. 8. Able to perform pulmonary function testing.
Exclusion criteria
1. Significant diseases other than asthma or allergic rhinitis. 2. Hepatic transaminases or total bilirubin greater than 1.5 ULN. 3. Hospitalisation for asthma exacerbation or asthma related intubation within 3 months. 4. Uncontrolled asthma on iCS + other controller. 5. Respiratory tract infection or exacerbation within 4 weeks. 6. FEV1 less than 40%, more than 12 puffs rescue salbutamol on more than two consecutive days, or asthma exacerbation during run-in period. 7. Participation in another interventional study. 8. Pregnant or nursing women. 9. Women of child bearing potential not using appropriate methods of birth control as defined by the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second (FEV1) % Predicted Trough Change From Baseline (Mean Observed in the 2 Weeks Prior to Treatment) After Six Weeks of Treatment | Measurements at baseline (mean observed in the 2 weeks prior to treatment) and at week 6 of treatment. | Forced expiratory volume in one second (FEV1) % predicted trough change from baseline (mean observed in the 2 weeks prior to treatment) after 6 weeks of treatment, where trough FEV1 % predicted was defined as the mean of the FEV1 % predicted trough values at 25 minutes and 10 minutes prior to dosing on clinic visit. MMRM in the statistical test comments is Mixed effects model with repeated measures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Control Questionnaire (ACQ) Mean Change in Score on a Scale From Baseline After Six Weeks of Treatment | Measurements at baseline (mean ACQ score obtained at Week 0) and at week 6 of treatment. | Asthma Control Questionnaire (ACQ) mean score change from baseline (mean ACQ score obtained at Week 0) after six weeks of treatment. The Asthma Control Questionnaire (ACQ) is a patient-reported outcome questionnaire containing 7 items. The items are equally weighted and the ACQ score is the mean of the 7 items and therefore between 0 (well controlled) and 6 (extremely poorly controlled) These questions based on recall of the previous 7 days comprise breathlessness, nocturnal waking, symptoms on waking, activity limitation, wheeze, frequency of Short-acting beta-adrenergic (SABA) use, and categorized pre-bronchodilator FEV1% predicted. |
Countries
Austria, Germany, Italy, New Zealand, South Korea, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This was a Phase IIa, multicentre, multinational, randomised, double-blind, double-dummy, placebo-controlled, parallel group study to assess the efficacy and safety of oral BI 671800 ED 400 mg b.i.d., montelukast 10 mg q.d., or placebo in symptomatic asthma patients on Fluticasone propionate Hydrofluoralkane Metered Dose Inhaler (100μg b.i.d.).
Pre-assignment details
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all subjects as required.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Daily treatment with 4 oral capsules of BI 671800 Ethylenediamine (ED) placebo in the morning and 4 oral capsules of BI 671800 ED placebo plus 1 over-encapsulated montelukast placebo tablet in the evening, for a total treatment period of 6 weeks. | 95 |
| BI 671800 400 mg Bid Daily treatment with 4 oral capsules of 100 milligram (mg) BI 67800 Ethylenediamine (ED) in the morning and 4 oral capsules of 100 mg BI 67800 ED plus 1 over-encapsulated montelukast placebo tablet in the evening, for a total treatment period of 6 weeks. | 81 |
| Montelukast 10 mg qd Daily treatment with 4 oral capsules of BI 67800 Ethylenediamine (ED) Placebo in the morning and 4 oral capsules of BI 67800 ED Placebo plus 1 table of 10 mg over-encapsulated montelukast in the evening, for a total treatment period of 6 weeks. | 67 |
| Total | 243 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 5 | 3 |
| Overall Study | Consent withdrawn | 1 | 0 | 0 |
| Overall Study | did not want to take trial medication | 0 | 1 | 0 |
| Overall Study | forgot to take medication | 0 | 0 | 1 |
| Overall Study | Incorrectly included in the trial | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | BI 671800 400 mg Bid | Montelukast 10 mg qd | Total |
|---|---|---|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 12.64 | 41.8 years STANDARD_DEVIATION 12.67 | 41.7 years STANDARD_DEVIATION 11.97 | 41.6 years STANDARD_DEVIATION 12.42 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 77 Participants | 65 Participants | 235 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Percentage of predicted forced expiratory volume in one second (FEV1) | 68.089 Percentage of predicted FEV1 STANDARD_DEVIATION 10.9109 | 69.286 Percentage of predicted FEV1 STANDARD_DEVIATION 10.5542 | 69.842 Percentage of predicted FEV1 STANDARD_DEVIATION 10.5288 | 68.986 Percentage of predicted FEV1 STANDARD_DEVIATION 10.6644 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 12 Participants | 6 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 2 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) White | 77 Participants | 66 Participants | 56 Participants | 199 Participants |
| Sex: Female, Male Female | 55 Participants | 50 Participants | 42 Participants | 147 Participants |
| Sex: Female, Male Male | 40 Participants | 31 Participants | 25 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 95 | 0 / 81 | 0 / 67 |
| other Total, other adverse events | 18 / 95 | 10 / 81 | 8 / 67 |
| serious Total, serious adverse events | 0 / 95 | 1 / 81 | 0 / 67 |
Outcome results
Primary
Forced Expiratory Volume in One Second (FEV1) % Predicted Trough Change From Baseline (Mean Observed in the 2 Weeks Prior to Treatment) After Six Weeks of Treatment
Forced expiratory volume in one second (FEV1) % predicted trough change from baseline (mean observed in the 2 weeks prior to treatment) after 6 weeks of treatment, where trough FEV1 % predicted was defined as the mean of the FEV1 % predicted trough values at 25 minutes and 10 minutes prior to dosing on clinic visit. MMRM in the statistical test comments is Mixed effects model with repeated measures.
Time frame: Measurements at baseline (mean observed in the 2 weeks prior to treatment) and at week 6 of treatment.
Population: Statistical analysis was performed on randomized patients who received at least one dose of treatment and had both baseline and the post-baseline measurement at 6 weeks for the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Forced Expiratory Volume in One Second (FEV1) % Predicted Trough Change From Baseline (Mean Observed in the 2 Weeks Prior to Treatment) After Six Weeks of Treatment | -0.859 FEV1 percent predicted | Standard Deviation 1.029 |
| BI 671800 400 mg Bid | Forced Expiratory Volume in One Second (FEV1) % Predicted Trough Change From Baseline (Mean Observed in the 2 Weeks Prior to Treatment) After Six Weeks of Treatment | 3.011 FEV1 percent predicted | Standard Deviation 1.082 |
| Montelukast 10 mg qd | Forced Expiratory Volume in One Second (FEV1) % Predicted Trough Change From Baseline (Mean Observed in the 2 Weeks Prior to Treatment) After Six Weeks of Treatment | 1.510 FEV1 percent predicted | Standard Deviation 1.181 |
Comparison: H0: Mean FEV1 % predicted trough change from baseline (BI671800 ED 400 mg bid) ≤ Mean FEV1 % predicted trough change from baseline (placebo)p-value: 0.00595% CI: [0.931, 6.809]Mixed Models Analysis
Comparison: H0: Mean FEV1 % predicted trough change from baseline (Montelukast 10 mg qd) ≤ Mean FEV1 % predicted trough change from baseline (placebo)p-value: 0.065795% CI: [-0.713, 5.452]Mixed Models Analysis
Comparison: H0: Mean FEV1 % predicted trough change from baseline (BI671800 ED 400 mg bid) ≤ Mean FEV1 % predicted trough change from baseline (Montelukast 10 mg qd)p-value: 0.174895% CI: [-1.652, 4.653]Mixed Models Analysis
Secondary
Asthma Control Questionnaire (ACQ) Mean Change in Score on a Scale From Baseline After Six Weeks of Treatment
Asthma Control Questionnaire (ACQ) mean score change from baseline (mean ACQ score obtained at Week 0) after six weeks of treatment. The Asthma Control Questionnaire (ACQ) is a patient-reported outcome questionnaire containing 7 items. The items are equally weighted and the ACQ score is the mean of the 7 items and therefore between 0 (well controlled) and 6 (extremely poorly controlled) These questions based on recall of the previous 7 days comprise breathlessness, nocturnal waking, symptoms on waking, activity limitation, wheeze, frequency of Short-acting beta-adrenergic (SABA) use, and categorized pre-bronchodilator FEV1% predicted.
Time frame: Measurements at baseline (mean ACQ score obtained at Week 0) and at week 6 of treatment.
Population: Statistical analysis was performed on randomized patients who received at least one dose of treatment and had both baseline and the post-baseline measurement at 6 weeks for the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Asthma Control Questionnaire (ACQ) Mean Change in Score on a Scale From Baseline After Six Weeks of Treatment | -0.418 Score on a scale | Standard Deviation 0.081 |
| BI 671800 400 mg Bid | Asthma Control Questionnaire (ACQ) Mean Change in Score on a Scale From Baseline After Six Weeks of Treatment | -0.698 Score on a scale | Standard Deviation 0.085 |
| Montelukast 10 mg qd | Asthma Control Questionnaire (ACQ) Mean Change in Score on a Scale From Baseline After Six Weeks of Treatment | -0.598 Score on a scale | Standard Deviation 0.093 |
p-value: 0.009295% CI: [-0.512, -0.048]Mixed Models Analysis
p-value: 0.073295% CI: [-0.423, 0.063]Mixed Models Analysis
p-value: 0.213995% CI: [-0.347, 0.147]Mixed Models Analysis