Asthma
Conditions
Brief summary
This is a 6 week study to investigate the effectiveness and safety of BI 671800 ED in patients with asthma who do not take inhaled corticosteroids.
Interventions
DRUGBI 671800
BI 671800
Placebo matching Fluticasone propionate
DRUGFluticasone propionate
Fluticasone propionate
DRUGBI 671800 Placebo
Placebo matching BI 671800
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% with 200 mL) asthma (according to GINA) with following spirometry at randomization: FEV1 60%-85%. 3. No ICS previous 3 months prior to screening. 4. Diagnosis of asthma prior to 40 years. 5. ACQ at least 1.5 at randomization. 6. Male or female, 18 to 65 years. 7. Non-smokers or ex-smokers ( less than 10 pack year history) with negative cotinine screen. 8. Able to perform PFT
Exclusion criteria
1. Significant diseases other than asthma or allergic rhinitis. 2. Hepatic transaminases or total bilirubin greater than 1.5 ULN. 3. Hospitalizations for asthma or asthma related intubation within 3 months. 4. Uncontrolled asthma. 5. Respiratory tract infection or exacerbation within 4 weeks. 6. FEV1 less than 40%, more than 12 puffs of SABA on more than two consecutive days or asthma exacerbation during the run-in period. 7. Participation in another interventional study. 8. Pregnant or nursing women. 9. Women of child bearing potential nor using appropriate methods of birth control as defined by 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 Score Change 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
Australia, Canada, Colombia, Mexico, New Zealand, Peru, Philippines, South Korea, Taiwan, United States
Participant flow
Recruitment details
This was a Phase IIa multi-centre, multi-national, randomized, double-blind, placebo-controlled, parallel group, double-dummy study investigating the efficacy, safety and tolerability of BI 671800 ED (50, 200 and 400 mg b.i.d.) compared to fluticasone propionate 110 mcg 2 puffs b.i.d. and placebo in symptomatic steroid-naïve asthma patients.
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 Placebo and 2 puffs Placebo metered dose inhaler (MDI) 110 microgram (mcg) in the morning and 4 oral capsules of Placebo and 2 puffs Placebo MDI 110 mcg in the evening, for a total treatment period of 6 weeks. | 78 |
| BI 671800 50 mg Bid Daily treatment with 2 oral capsules of 25 milligram (mg) BI 671800 Ethylenediamine (ED), 2 oral capsules of Placebo and 2 puffs Placebo metered dose inhaler (MDI) 110 microgram (mcg) in the morning and 2 oral capsules of 25 mg BI 671800 ED, 2 oral capsules of Placebo and 2 puffs Placebo MDI 110 mcg in the evening, for a total treatment period of 6 weeks. | 77 |
| BI 671800 200 mg Bid Daily treatment with oral 2 capsules of 100 milligram (mg) BI 671800 Ethylenediamine (ED), 2 oral capsules of Placebo and 2 puffs Placebo metered dose inhaler (MDI) 110 microgram (mcg) in the morning and 2 oral capsules of 100 mg BI 671800 ED, 2 oral capsules of Placebo and 2 puffs Placebo MDI 110 mcg in the evening, for a total treatment period of 6 weeks. | 83 |
| BI 671800 400 mg Bid Daily treatment with 4 oral capsules of 100 milligram (mg) BI 671800 Ethylenediamine (ED) and 2 puffs Placebo metered dose inhaler (MDI) 110 microgram (mcg) in the morning and 4 oral capsules of 100 mg BI 671800 ED and 2 puffs Placebo MDI 110 mcg in the evening, for a total treatment period of 6 weeks. | 79 |
| Fluticasone 220 mcg Bid Daily treatment with 4 oral capsules of Placebo and 2 puffs Fluticasone propionate metered dose inhaler (MDI) 110 microgram (mcg) in the morning and 4 oral capsules of Placebo and 2 puffs Fluticasone propionate MDI 110 mcg in the evening, for a total treatment period of 6 weeks. | 71 |
| Total | 388 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 | 1 | 4 | 3 |
| Overall Study | Consent withdrawn | 2 | 1 | 0 | 1 | 3 |
| Overall Study | did not reversibility criteria | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Drop in FEV1 at visit 9 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Increased Albuterol use for >2 days | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Ineligible patient | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Non compliance with study medication | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Not treated | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Patient travel | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Randomized by mistake | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | BI 671800 50 mg Bid | BI 671800 200 mg Bid | BI 671800 400 mg Bid | Fluticasone 220 mcg Bid | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 36.4 years STANDARD_DEVIATION 12.99 | 39.1 years STANDARD_DEVIATION 11.53 | 35.1 years STANDARD_DEVIATION 11.09 | 37.5 years STANDARD_DEVIATION 12.23 | 39.4 years STANDARD_DEVIATION 12.2 | 37.4 years STANDARD_DEVIATION 12.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 17 Participants | 20 Participants | 20 Participants | 23 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 58 Participants | 60 Participants | 57 Participants | 45 Participants | 276 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 12 Participants |
| Percentage of predicted forced expiratory volume in one second (FEV1) | 70.811 Percentage of predicted FEV1 STANDARD_DEVIATION 8.6801 | 68.812 Percentage of predicted FEV1 STANDARD_DEVIATION 10.6335 | 72.626 Percentage of predicted FEV1 STANDARD_DEVIATION 9.9901 | 71.646 Percentage of predicted FEV1 STANDARD_DEVIATION 7.4747 | 70.481 Percentage of predicted FEV1 STANDARD_DEVIATION 9.7577 | 70.904 Percentage of predicted FEV1 STANDARD_DEVIATION 9.4014 |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants | 10 Participants | 12 Participants | 13 Participants | 11 Participants | 57 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 13 Participants | 19 Participants | 13 Participants | 13 Participants | 71 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 11 Participants | 9 Participants | 10 Participants | 5 Participants | 47 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 42 Participants | 42 Participants | 43 Participants | 42 Participants | 42 Participants | 211 Participants |
| Sex: Female, Male Female | 37 Participants | 41 Participants | 42 Participants | 43 Participants | 36 Participants | 199 Participants |
| Sex: Female, Male Male | 41 Participants | 36 Participants | 41 Participants | 36 Participants | 35 Participants | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 78 | 0 / 77 | 0 / 83 | 0 / 79 | 0 / 71 |
| other Total, other adverse events | 14 / 78 | 15 / 77 | 9 / 83 | 14 / 79 | 11 / 71 |
| serious Total, serious adverse events | 1 / 78 | 0 / 77 | 0 / 83 | 1 / 79 | 0 / 71 |
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 the Full Analysis Set (FAS): Randomized patients who received at least one dose of treatment and had both baseline and at least one post-baseline measurement at or before 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 | -2.010 FEV1 percent predicted | Standard Deviation 1.187 |
| BI 671800 50 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 | 1.073 FEV1 percent predicted | Standard Deviation 1.144 |
| BI 671800 200 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 | 1.580 FEV1 percent predicted | Standard Deviation 1.074 |
| 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 | 1.967 FEV1 percent predicted | Standard Deviation 1.133 |
| Fluticasone 220 mcg 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 | 6.610 FEV1 percent predicted | Standard Deviation 1.194 |
Comparison: Superiority in mean trough FEV1 % predicted change from baseline in patients treated with BI 671800 50 mg b.i.d. compared with those treated with placebo, after 6 weeks.p-value: 0.031195% CI: [-0.157, 6.323]Mixed Models Analysis
Comparison: Superiority in mean trough FEV1 % predicted change from baseline in patients treated with BI 671800 200 mg b.i.d. compared with those treated with placebo, after 6 weeks.p-value: 0.012695% CI: [0.447, 6.732]Mixed Models Analysis
Comparison: Superiority in mean trough FEV1 % predicted change from baseline in patients treated with BI 671800 400 mg b.i.d. compared with those treated with placebo, after 6 weeks.p-value: 0.007895% CI: [0.756, 7.197]Mixed Models Analysis
Comparison: Superiority in mean trough FEV1 % predicted change from baseline in patients treated with fluticasone propionate 110 mcg 2 puffs b.i.d. compared with those treated with placebo, after 6 weeks.p-value: <0.000195% CI: [5.312, 11.927]Mixed Models Analysis
Comparison: Superiority in mean trough FEV1 % predicted change from baseline in patients treated with BI 671800 50 mg b.i.d. compared with those treated with fluticasone propionate 220 mcg b.i.d., after 6 weeks.p-value: 0.999695% CI: [-8.783, -2.29]Mixed Models Analysis
Comparison: Superiority in mean trough FEV1 % predicted change from baseline in patients treated with BI 671800 200 mg b.i.d. compared with those treated with fluticasone propionate 220mcg b.i.d., after 6 weeks.p-value: 0.999195% CI: [-8.185, -1.875]Mixed Models Analysis
Comparison: Superiority in mean trough FEV1 % predicted change from baseline in patients treated with BI 671800 400 mg b.i.d. compared with those treated with fluticasone propionate 220 mcg b.i.d., after 6 weeks.p-value: 0.997595% CI: [-7.877, -1.408]Mixed Models Analysis
Secondary
Asthma Control Questionnaire (ACQ) Mean Score Change 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 the Full Analysis Set (FAS): Randomized patients who received at least one dose of treatment and had both baseline and at least one post-baseline measurement at or before 6 weeks for the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Asthma Control Questionnaire (ACQ) Mean Score Change From Baseline After Six Weeks of Treatment | -0.616 Score on a scale | Standard Deviation 0.081 |
| BI 671800 50 mg Bid | Asthma Control Questionnaire (ACQ) Mean Score Change From Baseline After Six Weeks of Treatment | -0.543 Score on a scale | Standard Deviation 0.078 |
| BI 671800 200 mg Bid | Asthma Control Questionnaire (ACQ) Mean Score Change From Baseline After Six Weeks of Treatment | -0.696 Score on a scale | Standard Deviation 0.074 |
| BI 671800 400 mg Bid | Asthma Control Questionnaire (ACQ) Mean Score Change From Baseline After Six Weeks of Treatment | -0.677 Score on a scale | Standard Deviation 0.078 |
| Fluticasone 220 mcg Bid | Asthma Control Questionnaire (ACQ) Mean Score Change From Baseline After Six Weeks of Treatment | -0.949 Score on a scale | Standard Deviation 0.082 |
p-value: 0.741395% CI: [-0.149, 0.295]Mixed Models Analysis
p-value: 0.233595% CI: [-0.296, 0.136]Mixed Models Analysis
p-value: 0.293395% CI: [-0.282, 0.16]Mixed Models Analysis
p-value: 0.002195% CI: [-0.561, -0.105]Mixed Models Analysis
p-value: 0.999895% CI: [0.183, 0.63]Mixed Models Analysis
p-value: 0.98995% CI: [0.037, 0.47]Mixed Models Analysis
p-value: 0.991895% CI: [0.05, 0.494]Mixed Models Analysis