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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001506-42 | EudraCT Number |
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The primary objective of this study is to investigate safety and tolerability of three consecutive administrations, 12 hours apart, at three different dose-levels of BI 443651 administered via oral inhalation in male and female mild asthmatic subjects after a bolus methacholine challenge.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 443651 | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 443651 | Drug | Three doses, each 12 hours apart |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 1 | Absolute change from baseline in maximum forced expiratory volume within 1 second (FEV1) reduction following bolus methacholine challenge in Part 1 was defined as the difference between the maximum reduction in FEV1 obtained during the treatment challenge and during the baseline challenge. | Baseline and Day 2 |
| Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 2. | Absolute change from baseline in maximum FEV1 reduction following bolus methacholine challenge in Part 2 was defined as the difference between the maximum reduction in FEV1 obtained during the treatment challenge and during the baseline challenge. | Baseline and Day 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Relative Change From Baseline in FEV1 Area Under the Curve Over the Time Interval From 0 to Timepoint tz (FEV1 AUC0-tz) Following Bolus Methacholine Challenge in Part 1 | Relative change from baseline in FEV1 area under the curve over the time interval from 0 to timepoint tz (FEV1 AUC0-tz) following bolus methacholine challenge in Part 1 was defined as the ratio of FEV1 AUC0-tz obtained during the treatment challenge and during the baseline challenge, where the time tz refers to the last time point before recovery of FEV1 to within 95% of post-diluent value. |
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Inclusion criteria:
Male or female subjects must have a diagnosis of asthma by a physician at least 3 months prior to screening. The diagnosis of asthma must meet the following spirometric criteria:
-- Pre-bronchodilator clinic measured FEV1 >=70% of predicted normal (calculated by the Global Lung Function Initiative equation (GLI)) measured >= 8 hours after the last use of short acting bronchodilator at the screening visit and on the day of randomisation.
Age >= 18 <= 60 years. Subjects must be within the eligible age range on the day of signing informed consent.
Diagnosis of asthma must have been made before the subject's age of 40. Or If the subject is >= 40 years and the diagnosis has not yet been recorded in the subject's medical files, the investigator should assess whether the subject's medical history (e.g. symptoms and prescribed medications) confirms the subject suffered from asthma since before the age of 40. If so, this subject may be considered for inclusion after consultation with the sponsor.
ACQ value < 1.5 at the screening visit.
PD20 (Provocative dose causing at least a 20% decline in FEV1) at the screening visit of methacholine <= 1mg
Body mass index (BMI) >= 18.5 and <= 32.0 kg/m2 at the screening visit
Subjects must be able to perform all study related procedures and assessments, including pulmonary function tests, as required by the protocol.
Exclusion criteria:
Significant pulmonary diseases other than asthma (up to GINA treatment step 2) or other medical conditions (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator result in any of the following:
Respiratory tract infection or asthma exacerbation in the 4 weeks prior to the screening visit. Subjects can be rescreened 4 weeks after resolution of the infection or exacerbation.
Hospitalisation for asthma exacerbation within 3 months or intubation for asthma within 3 years of the screening visit.
Serum potassium measurement above the ULN at the screening visit. Any value about the ULN excludes the subject irrespective of clinical relevance.
Blood donation (more than 100mL within 30 days prior to the administration of trial medication or intended during the trial)
Subjects who have been treated with any of the following asthma medications in the given interval prior to Visit 1:
Use of any diuretics (including loop diuretics or potassium sparing diuretics (such as amiloride), renin-angiotensin antihypertensive drugs in the 28 days prior to the screening visit (Visit 1)
Use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval within 10 days prior to the randomisation visit.
A marked baseline prolongation of QT/QTcF interval (such as QTcF intervals that are repeatedly greater than 450 ms in males or repeatedly greater than 470 ms in females) or any other relevant ECG finding at screening and prior to randomisation
A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
History of relevant allergies/hypersensitivities (including allergy to the trial medication or its excipients)
Contraceptive measures for male and female patients may be required
Current smokers or ex-smokers who have given up smoking for < 12 months and / or have a smoking pack history of > 5 pack years (1 pack year = 20 cigarettes per day for 1 year of 5 cigarettes per day for 4 years)
Further exclusion criteria apply
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Medicines Evaluation Unit | Manchester | M23 9QZ | United Kingdom |
All patients were screened for eligibility to participate in the trial. Patients attended a specialist site which ensured that they (the patients) met all strictly implemented inclusion/exclusion criteria. Patients were not to be randomized to trial treatment if any one of the specific entry criteria was violated.
Patients with mild asthma were recruited in this trial, which was split into 2 parts. Part 1 was a multiple-dose, single-blind, double-dummy, randomized, 4-way crossover trial with dose ordered sequences. Part 2 was a multiple-dose, double-blind, double-dummy, randomized, 4-way crossover trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo/BI 443651 100/400/1200 Micro Gram (μg) - Part 1 | Patients were orally administered placebo matched to BI 443651 inhalation solution in period 1, followed by BI 443651 100 micro gram (μg) inhalation solution in period 2, BI 443651 400 μg inhalation solution in period 3 and BI 443651 1200 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| FG001 | BI 443651 100 μg/Placebo/BI 443651 400/1200 μg - Part 1 | Patients were orally administered BI 443651 100 μg inhalation solution in period 1, followed by placebo matched to BI 443651 inhalation solution in period 2, BI 443651 400 μg inhalation solution in period 3 and BI 443651 1200 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| FG002 | BI 443651 100/400 μg/Placebo/BI 443651 1200 μg - Part 1 | Patients were orally administered BI 443651 100 μg inhalation solution in period 1, followed by BI 443651 400 μg inhalation solution in period 2, placebo matched to BI 443651 inhalation solution in period 3 and BI 443651 1200 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| FG003 | BI 443651 100/400/1200 μg/Placebo - Part 1 | Patients were orally administered BI 443651 100 μg inhalation solution in period 1, followed by BI 443651 400 μg inhalation solution in period 2, BI 443651 1200 μg inhalation solution in period 3 and placebo matched to BI 443651 inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| FG004 | Placebo/BI 443651 100/400/1200 μg - Part 2 | Patients were orally administered placebo matched to BI 443651 inhalation solution in period 1, followed by BI 443651 100 μg inhalation solution in period 2, BI 443651 400 μg inhalation solution in period 3 and BI 443651 1200 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| FG005 | BI 443651 400/1200 μg/Placebo/BI 443651 100 μg - Part 2 | Patients were orally administered BI 443651 400 μg inhalation solution in period 1, followed by BI 443651 1200 μg inhalation solution in period 2, placebo matched to BI 443651 inhalation solution in period 3 and BI 443651 100 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| FG006 | BI 443651 100 μg/Placebo/BI 443651 1200/400 μg - Part 2 | Patients were orally administered BI 443651 100 μg inhalation solution in period 1, followed by placebo matched to BI 443651 inhalation solution in period 2, BI 443651 1200 μg inhalation solution in period 3 and BI 443651 400 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| FG007 | BI 443651 1200/400/100 μg/Placebo - Part 2 | Patients were orally administered BI 443651 1200 μg inhalation solution in period 1, followed by BI 443651 400 μg inhalation solution in period 2, BI 443651 100 μg inhalation solution in period 3 and placebo matched to BI 443651 inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated set (TS): The TS included all patients who had been randomised and treated with at least 1 dose of trial medication. The treatment assignment was determined based on the first treatment the patients received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo/BI 443651 100/400/1200 Micro Gram (μg) - Part 1 | Patients were orally administered placebo matched to BI 443651 inhalation solution in period 1, followed by BI 443651 100 micro gram (μg) inhalation solution in period 2, BI 443651 400 μg inhalation solution in period 3 and BI 443651 1200 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 1 | Absolute change from baseline in maximum forced expiratory volume within 1 second (FEV1) reduction following bolus methacholine challenge in Part 1 was defined as the difference between the maximum reduction in FEV1 obtained during the treatment challenge and during the baseline challenge. | Methacholine set (MCS): The MCS included all patients in the TS who provided at least one pair (baseline and end-of-treatment) of evaluable measures of spirometry parameters that were not excluded due to use of rescue medication within 3 hours (h) after start of bolus methacholine challenge. | Posted | Mean | Standard Deviation | Litres (L) | Baseline and Day 2 |
|
From the first drug administration until 14 days after the last drug administration, up to 16 days.
Treated set (TS): The TS included all patients who had been randomised and treated with at least 1 dose of trial medication. The treatment assignment was determined based on the first treatment the patients received.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo - Part 1 & Part 2 | Patients were orally administered 4 actuations of placebo matched with BI 443651 inhalation solution via Respimat® inhaler. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest discomfort | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 23, 2017 | Nov 6, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 23, 2018 | Nov 6, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| Drug |
Three doses, each 12 hours apart |
|
| Baseline and Day 2 |
| Relative Change From Baseline in FEV1 Area Under the Curve Over the Time Interval From 0 to Timepoint tz (FEV1 AUC0-tz) Following Bolus Methacholine Challenge in Part 2 | Relative change from baseline in FEV1 area under the curve over the time interval from 0 to timepoint tz (FEV1 AUC0-tz) following bolus methacholine challenge in Part 2 was defined as the ratio of FEV1 AUC0-tz obtained during the treatment challenge and during the baseline challenge, where the time tz refers to the last time point before recovery of FEV1 to within 95% of post-diluent value. Geometric mean is actually adjusted geometric mean. Standard error presented here is a geometric standard error. | Baseline and Day 2 |
| Time to Recovery of FEV1 to Within 95% of Post-diluent Value in Part 1 | Time to recovery of FEV1 to within 95% of post-diluent value in Part 1 was defined as the time from maximum reduction to last time before recovery to within 95% of the value obtained pre-methacholine challenge during the respective challenge. | Day 2 |
| Time to Recovery of FEV1 to Within 95% of Post-diluent Value in Part 2 | Time to recovery of FEV1 to within 95% of post-diluent value in Part 2 was defined as the time from maximum reduction to last time before recovery to within 95% of the value obtained pre-methacholine challenge during the respective challenge. Median is actually model-based median. | Day 2 |
| Withdrawal by Subject |
|
| BG001 | BI 443651 100 μg/Placebo/BI 443651 400/1200 μg - Part 1 | Patients were orally administered BI 443651 100 μg inhalation solution in period 1, followed by placebo matched to BI 443651 inhalation solution in period 2, BI 443651 400 μg inhalation solution in period 3 and BI 443651 1200 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| BG002 | BI 443651 100/400 μg/Placebo/BI 443651 1200 μg - Part 1 | Patients were orally administered BI 443651 100 μg inhalation solution in period 1, followed by BI 443651 400 μg inhalation solution in period 2, placebo matched to BI 443651 inhalation solution in period 3 and BI 443651 1200 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| BG003 | BI 443651 100/400/1200 μg/Placebo - Part 1 | Patients were orally administered BI 443651 100 μg inhalation solution in period 1, followed by BI 443651 400 μg inhalation solution in period 2, BI 443651 1200 μg inhalation solution in period 3 and placebo matched to BI 443651 inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| BG004 | Placebo/BI 443651 100/400/1200 μg - Part 2 | Patients were orally administered placebo matched to BI 443651 inhalation solution in period 1, followed by BI 443651 100 μg inhalation solution in period 2, BI 443651 400 μg inhalation solution in period 3 and BI 443651 1200 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| BG005 | BI 443651 400/1200 μg/Placebo/BI 443651 100 μg - Part 2 | Patients were orally administered BI 443651 400 μg inhalation solution in period 1, followed by BI 443651 1200 μg inhalation solution in period 2, placebo matched to BI 443651 inhalation solution in period 3 and BI 443651 100 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| BG006 | BI 443651 100 μg/Placebo/BI 443651 1200/400 μg - Part 2 | Patients were orally administered BI 443651 100 μg inhalation solution in period 1, followed by placebo matched to BI 443651 inhalation solution in period 2, BI 443651 1200 μg inhalation solution in period 3 and BI 443651 400 μg inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| BG007 | BI 443651 1200/400/100 μg/Placebo - Part 2 | Patients were orally administered BI 443651 1200 μg inhalation solution in period 1, followed by BI 443651 400 μg inhalation solution in period 2, BI 443651 100 μg inhalation solution in period 3 and placebo matched to BI 443651 inhalation solution in period 4, each treatment was administered via Respimat® inhaler. All treatment periods were separated by a washout period of 14-28 days. |
| BG008 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | BI 443651 100 μg - Part 1 | Patients were orally administered 1 actuation of BI 443651 100 μg inhalation solution via Respimat® inhaler. |
| OG002 | BI 443651 400 μg - Part 1 | Patients were orally administered 4 actuations, thrice 12 h apart, of BI 443651 100 μg inhalation solution via Respimat® inhaler. |
| OG003 | BI 443651 1200 μg - Part 1 | Patients were orally administered 4 actuations, thrice 12 h apart, of BI 443651 300 μg inhalation solution via Respimat® inhaler. |
|
|
| Primary | Absolute Change From Baseline in Maximum Forced Expiratory Volume Within 1 Second (FEV1) Reduction Following Bolus Methacholine Challenge in Part 2. | Absolute change from baseline in maximum FEV1 reduction following bolus methacholine challenge in Part 2 was defined as the difference between the maximum reduction in FEV1 obtained during the treatment challenge and during the baseline challenge. | MCS | Posted | Least Squares Mean | Standard Error | Litres (L) | Baseline and Day 2 |
|
|
|
|
| Secondary | Relative Change From Baseline in FEV1 Area Under the Curve Over the Time Interval From 0 to Timepoint tz (FEV1 AUC0-tz) Following Bolus Methacholine Challenge in Part 1 | Relative change from baseline in FEV1 area under the curve over the time interval from 0 to timepoint tz (FEV1 AUC0-tz) following bolus methacholine challenge in Part 1 was defined as the ratio of FEV1 AUC0-tz obtained during the treatment challenge and during the baseline challenge, where the time tz refers to the last time point before recovery of FEV1 to within 95% of post-diluent value. | MCS | Posted | Mean | Standard Deviation | Ratio | Baseline and Day 2 |
|
|
|
| Secondary | Relative Change From Baseline in FEV1 Area Under the Curve Over the Time Interval From 0 to Timepoint tz (FEV1 AUC0-tz) Following Bolus Methacholine Challenge in Part 2 | Relative change from baseline in FEV1 area under the curve over the time interval from 0 to timepoint tz (FEV1 AUC0-tz) following bolus methacholine challenge in Part 2 was defined as the ratio of FEV1 AUC0-tz obtained during the treatment challenge and during the baseline challenge, where the time tz refers to the last time point before recovery of FEV1 to within 95% of post-diluent value. Geometric mean is actually adjusted geometric mean. Standard error presented here is a geometric standard error. | MCS | Posted | Geometric Mean | Standard Error | Ratio | Baseline and Day 2 |
|
|
|
|
| Secondary | Time to Recovery of FEV1 to Within 95% of Post-diluent Value in Part 1 | Time to recovery of FEV1 to within 95% of post-diluent value in Part 1 was defined as the time from maximum reduction to last time before recovery to within 95% of the value obtained pre-methacholine challenge during the respective challenge. | MCS | Posted | Median | Inter-Quartile Range | hours (h) | Day 2 |
|
|
|
| Secondary | Time to Recovery of FEV1 to Within 95% of Post-diluent Value in Part 2 | Time to recovery of FEV1 to within 95% of post-diluent value in Part 2 was defined as the time from maximum reduction to last time before recovery to within 95% of the value obtained pre-methacholine challenge during the respective challenge. Median is actually model-based median. | MCS | Posted | Median | 95% Confidence Interval | h | Day 2 |
|
|
|
|
| 0 |
| 35 |
| 0 |
| 35 |
| 9 |
| 35 |
| EG001 | BI 443651 100 Microgram (μg) - Part 1 & Part 2 | Patients were orally administered 1 actuation of BI 443651 100 μg inhalation solution via Respimat® inhaler. | 0 | 35 | 0 | 35 | 21 | 35 |
| EG002 | BI 443651 400 μg - Part 1 & Part 2 | Patients were orally administered 4 actuations of BI 443651 100 μg inhalation solution via Respimat® inhaler. | 0 | 36 | 0 | 36 | 24 | 36 |
| EG003 | BI 443651 1200 μg - Part 1 & Part 2 | Patients were orally administered 4 actuations of BI 443651 300 μg inhalation solution via Respimat® inhaler. | 0 | 36 | 0 | 36 | 26 | 36 |
| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Procedural complication | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| The mixed effects model included 'treatment' and 'period' as fixed effects, 'patient' as a random effect, and 'period baseline' as well as 'patient baseline' as covariates. No hypothesis was tested. The patient baseline was obtained by calculating the mean of the period baselines for each patient. Covariance structure variance component (VC) was used for random subject effect. | Mixed Models Analysis | Mean Difference (Final Values) | -0.037 | Standard Error of the Mean | 0.064 | 2-Sided | 90 | -0.144 | 0.070 | BI 443651 400 μg is compared to placebo. | Other |
| The mixed effects model included 'treatment' and 'period' as fixed effects, 'patient' as a random effect, and 'period baseline' as well as 'patient baseline' as covariates. No hypothesis was tested. The patient baseline was obtained by calculating the mean of the period baselines for each patient. Covariance structure variance component (VC) was used for random subject effect. | Mixed Models Analysis | Mean Difference (Final Values) | -0.157 | Standard Error of the Mean | 0.066 | 2-Sided | 90 | -0.266 | -0.047 | BI 443651 1200 μg is compared to placebo. | Other |
| The mixed effects model included 'treatment' and 'period' as fixed effects, 'patient' as a random effect, and 'period baseline' as well as 'patient baseline' as covariates. No hypothesis was tested. The patient baseline was obtained by calculating the mean of the period baselines for each patient. Covariance structure variance component (VC) was used for random subject effect. | Mixed Models Analysis | Geometric Mean Ratio | 0.926 | Standard Error of the Mean | 1.168 | 2-Sided | 90 | 0.715 | 1.199 | BI 443651 400 μg is compared to placebo. Standard error of the mean is actually geometric standard error. | Other |
| The mixed effects model included 'treatment' and 'period' as fixed effects, 'patient' as a random effect, and 'period baseline' as well as 'patient baseline' as covariates. No hypothesis was tested. The patient baseline was obtained by calculating the mean of the period baselines for each patient. Covariance structure variance component (VC) was used for random subject effect. | Mixed Models Analysis | Geometric Mean Ratio | 0.845 | Standard Error of the Mean | 1.169 | 2-Sided | 90 | 0.651 | 1.095 | BI 443651 1200 μg is compared to placebo. Standard error of the mean is actually geometric standard error. | Other |
| The cox proportional hazard model included treatment and period as fixed effect and patient baseline as covariate. No hypothesis was tested. The patient baseline was obtained by calculating the median of the period baselines for each patient. A hazard ratio greater than 1 gives that active treatment is not-inferior to placebo. | Regression, Cox | Hazard Ratio (HR) | 2.08 | 2-Sided | 95 | 1.22 | 3.53 | BI 443651 400 μg is compared to placebo. | Other |
| The cox proportional hazard model included treatment and period as fixed effect and patient baseline as covariate. No hypothesis was tested. The patient baseline was obtained by calculating the median of the period baselines for each patient. A hazard ratio greater than 1 gives that active treatment is not-inferior to placebo. | Regression, Cox | Hazard Ratio (HR) | 2.59 | 2-Sided | 95 | 1.50 | 4.47 | BI 443651 1200 μg is compared to placebo. | Other |