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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001789-25 | EudraCT Number |
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The primary and secondary objectives of the current study are the assessments of anti-inflammatory pharmacodynamic effects on segmental endotoxin induced inflammatory response after 4 weeks treatment with BI 1026706.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 1026706 | Experimental |
| |
| Placebo | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 1026706 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Total Cell Count of Neutrophils in Bronchoalveolar Lavage (BAL) Fluid After 24 Hours of the Segmental Lipopolysaccharide (LPS) Challenge | Total cell count of neutrophils in Bronchoalveolar Lavage (BAL) fluid after 24 hours of the segmental Lipopolysaccharide (LPS) challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the Least Square (LS) means obtained by fitting an Analysis of variance (ANOVA) model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | Day 29 |
| Measure | Description | Time Frame |
|---|---|---|
| Differential Cell Count of Neutrophils in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of neutrophils in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. |
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Inclusion criteria:
Exclusion criteria:
History of any relevant lung disease (i.e. Chronic Obstructive Pulmonary Disease (COPD), asthma, chronic bronchitis, pulmonary fibrosis, pulmonary alveolar proteinosis (PAP), pneumocystis infection, active tuberculosis, silicosis or any other lung surfactant overproduction syndromes).
Subjects with clinically relevant abnormal hematology, blood chemistry, or urinalysis at the screening visit
Any finding of the medical examination (including blood pressure, pulse rate, body temperature and ECG) deviating from normal and of clinical relevance.
Subjects with a history of any clinically significant cardiovascular, metabolic, renal (including renal stones), hepatic, gastrointestinal, hematological, dermatological, venereal, neurological, psychiatric or other major disorders.
Subjects with a malignancy for which the subject has undergone resection, radiation therapy or chemotherapy within the last five years. Subjects with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed to participate.
Subjects with previous surgery of the gastro-intestinal tract likely to affect drug absorption.
History of relevant orthostatic hypotension, fainting spells or blackouts.
Subjects with clinically relevant infection or known ongoing clinically relevant inflammatory process.
History of relevant allergy/hypersensitivity including allergy to drug or its excipients or medications in line with bronchoscopy (bronchodilators, sedatives and local anesthetics).
Subjects with a marked baseline prolongation of QT/QTcB interval (such as repeated demonstration of a QTcB interval >450 ms), or any other relevant ECG finding at screening visit (Visit 1) according to the investigator.
Neutrophil blood count indicative of immunosuppression according to the investigator at screening visit (Visit 1).
Subjects with previous surgeries that may have left ferromagnetic material in the body, ferromagnetic implants or pacemakers.
Participation in another study with any investigational product within 2 months prior to screening or if screening occurs within 6 half-lives of intake of another investigational drug (whichever is greater).
Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until 3 months after the trial medication treatment has finished.
Subjects who are committed to an institution by way of official or juridical order will not be enrolled in the trial.
Receipt of live (attenuated) vaccine within the 4 weeks prior to screening or during the trial.
Subject is assessed as unsuitable for inclusion by the investigator; for instance, because he is not considered able to understand and comply with study requirements or has a condition that would not allow safe participation in the study.
For female subjects:
Further exclusion criteria apply
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fraunhofer ITEM | Hanover | 30625 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37562641 | Derived | Gress C, Vogel-Claussen J, Badorrek P, Muller M, Hohl K, Konietzke M, Litzenburger T, Seibold W, Gupta A, Hohlfeld JM. The effect of bradykinin 1 receptor antagonist BI 1026706 on pulmonary inflammation after segmental lipopolysaccharide challenge in healthy smokers. Pulm Pharmacol Ther. 2023 Oct;82:102246. doi: 10.1016/j.pupt.2023.102246. Epub 2023 Aug 9. |
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All subjects (Subjs) were screened for eligibility to participate in trial. Subjs attended specialist site to ensure that they (the Subjs) met all implemented inclusion/exclusion criteria. Subjs were not to be randomised to trial drug if any of specific entry criteria was violated.
This was a randomised, placebo-controlled, double-blind, parallel-group study in a single trial center. In this study 57 healthy smoking subjects were entered and randomized. Subjects were allowed to rescreened twice based on investigator´s judgment with new informed consent & unique study subject number.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28. |
| FG001 | BI 1026706 | Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated set: The treated set included all subjects who were randomized and treated with at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28. |
| BG001 | BI 1026706 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Treated Set |
| 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 | Total Cell Count of Neutrophils in Bronchoalveolar Lavage (BAL) Fluid After 24 Hours of the Segmental Lipopolysaccharide (LPS) Challenge | Total cell count of neutrophils in Bronchoalveolar Lavage (BAL) fluid after 24 hours of the segmental Lipopolysaccharide (LPS) challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the Least Square (LS) means obtained by fitting an Analysis of variance (ANOVA) model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | Pharmacodynamic set (PDS): The pharmacodynamic set included all treated subjects who had evaluable cell counts for the primary or secondary endpoints 24 h after segmental LPS challenge. | Posted | Geometric Mean | Standard Error | cells*10^3/mililiter (mL) | Day 29 |
|
From first dose administration of the study medication to 4 days after last drug administration; up to 35 days.
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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 | Subjects were orally treated with matching placebo as film-coated tablets twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Post procedural complication | Injury, poisoning and procedural complications | 19.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | 19.1 | 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 | Dec 19, 2016 | Dec 10, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 23, 2017 | Dec 10, 2018 | SAP_001.pdf |
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| Day 29 |
| Total Cell Count of Eosinophil in BAL Fluid After 24 Hours of the Segmental LPS Challenge | Total cell count of eosinophil in BAL fluid after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | Day 29 |
| Differential Cell Count of Eosinophil in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of eosinophil in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | Day 29 |
| Total Cell Count of Monocyte in BAL Fluid After 24 Hours of the Segmental LPS Challenge | Total cell count of monocyte in BAL fluid after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Monocyte cell count is the only cell count which was assessed by means of flow cytometry. | Day 29 |
| Differential Cell Count of Monocyte in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of monocyte (determined by flow cytometry) in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Monocyte cell count is the only cell count which was assessed by means of flow cytometry. | Day 29 |
| Total Cell Count of Macrophage+Monocyte in BAL Fluid After 24 Hours of the Segmental LPS Challenge | Total cell count of macrophage+monocyte BAL fluid after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Cytospin microscopy method cannot clearly differentiate between macrophages and monocytes, the total and differential cell count of macrophages and monocytes are presented together. | Day 29 |
| Differential Cell Count of Macrophage+Monocyte in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of macrophage+monocyte in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Cytospin microscopy method cannot clearly differentiate between macrophages and monocytes, the total and differential cell count of macrophages and monocytes are presented together. | Day 29 |
| Total Cell Count of Lymphocyte in BAL After 24 Hours of the Segmental LPS Challenge | Total cell count of lymphocyte after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | Day 29 |
| Differential Cell Count of Lymphocyte in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of lymphocyte in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | Day 29 |
Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28.
| BG002 | Total | Total of all reporting groups |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Treated set | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Treated set | Count of Participants | Participants |
|
| Race (NIH/OMB) | All subjects were white in this trial | Treated set | Count of Participants | Participants |
|
| Total neutrophil count | Total neutrophil count at baseline (Visit6) | Pharmacodynamic set (PDS): The pharmacodynamic set included all treated subjects who had evaluable cell counts for the primary or secondary endpoints 24 h after segmental LPS challenge. | Mean | Standard Deviation | cells*10^3/mL |
|
| OG001 | BI 1026706 | Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28. |
|
|
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| Secondary | Differential Cell Count of Neutrophils in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of neutrophils in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | PDS | Posted | Geometric Mean | Standard Error | Percentage of neutrophils | Day 29 |
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| Secondary | Total Cell Count of Eosinophil in BAL Fluid After 24 Hours of the Segmental LPS Challenge | Total cell count of eosinophil in BAL fluid after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | PDS | Posted | Geometric Mean | Standard Error | cells*10^3/mL | Day 29 |
|
|
|
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| Secondary | Differential Cell Count of Eosinophil in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of eosinophil in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | PDS | Posted | Geometric Mean | Standard Error | Percentage of eosinophil | Day 29 |
|
|
|
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| Secondary | Total Cell Count of Monocyte in BAL Fluid After 24 Hours of the Segmental LPS Challenge | Total cell count of monocyte in BAL fluid after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Monocyte cell count is the only cell count which was assessed by means of flow cytometry. | PDS | Posted | Geometric Mean | Standard Error | cells*10^3/mL | Day 29 |
|
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| Secondary | Differential Cell Count of Monocyte in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of monocyte (determined by flow cytometry) in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Monocyte cell count is the only cell count which was assessed by means of flow cytometry. | PDS | Posted | Geometric Mean | Standard Error | Percentage of monocyte | Day 29 |
|
|
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| Secondary | Total Cell Count of Macrophage+Monocyte in BAL Fluid After 24 Hours of the Segmental LPS Challenge | Total cell count of macrophage+monocyte BAL fluid after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Cytospin microscopy method cannot clearly differentiate between macrophages and monocytes, the total and differential cell count of macrophages and monocytes are presented together. | PDS | Posted | Geometric Mean | Standard Error | cells*10^3/mL | Day 29 |
|
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| Secondary | Differential Cell Count of Macrophage+Monocyte in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of macrophage+monocyte in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. Cytospin microscopy method cannot clearly differentiate between macrophages and monocytes, the total and differential cell count of macrophages and monocytes are presented together. | PDS | Posted | Geometric Mean | Standard Error | Percentage of macrophage+monocyte | Day 29 |
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| Secondary | Total Cell Count of Lymphocyte in BAL After 24 Hours of the Segmental LPS Challenge | Total cell count of lymphocyte after 24 hours of the segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | PDS | Posted | Geometric Mean | Standard Error | cells*10^3/mL | Day 29 |
|
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| Secondary | Differential Cell Count of Lymphocyte in BAL Fluid 24 h After Segmental LPS Challenge. | Differential cell count of lymphocyte in BAL fluid 24 h after segmental LPS challenge. The adjusted geometric means (gMeans) are obtained by exponentiating the LS means obtained by fitting an ANOVA model on the natural log transformed endpoint values, adjusted for treatment effect. Standard errors are derived using the delta method. | PDS | Posted | Geometric Mean | Standard Error | Percentage of lymphocyte | Day 29 |
|
|
|
|
| 0 |
| 28 |
| 1 |
| 28 |
| 21 |
| 28 |
| EG001 | BI 1026706 | Subjects were orally treated with BI 1026706 as film-coated tablets 100 mg twice daily in the morning and evening from beginning on Day 1 (Visit 2) until Day 28. | 0 | 29 | 1 | 29 | 18 | 29 |
| Presyncope | Nervous system disorders | 19.1 | Systematic Assessment |
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| Calculus urinary | Renal and urinary disorders | 19.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | 19.1 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | 19.1 | Systematic Assessment |
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| Pyrexia | General disorders | 19.1 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | 19.1 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | 19.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | 19.1 | Systematic Assessment |
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| Post procedural complication | Injury, poisoning and procedural complications | 19.1 | Systematic Assessment |
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| Procedural complication | Injury, poisoning and procedural complications | 19.1 | Systematic Assessment |
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| Procedural headache | Injury, poisoning and procedural complications | 19.1 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | 19.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | 19.1 | Systematic Assessment |
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| Headache | Nervous system disorders | 19.1 | Systematic Assessment |
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| Agitation | Psychiatric disorders | 19.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
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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.
| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
|