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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-005451-16 | EudraCT Number | EudraCT |
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The main objective of the current trial is to investigate safety, tolerability and pharmacokinetics of BI 113608 in COPD patients with symptoms of chronic bronchitis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 113608 low dose b.i.d. | Experimental | Film-coated tablet, oral administration with 240 mL water |
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| BI 113608 medium dose b.i.d. | Experimental | Film-coated tablet, oral administration with 240 mL water |
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| BI 113608 high dose b.i.d. | Experimental | Film-coated tablet, oral administration with 240 mL water |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo to BI 113608 high dose b.i.d. | Drug | Film-coated tablet |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number (%) of Patients With Drug-related Adverse Events (AEs) | Number (%) of patients with drug-related adverse events (AEs) | AE's occuring upto end of treatment + 3 days follow up (Up to 31 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax,ss | Cmax,ss (maximum measured concentration of BI 113608 in plasma at steady state over a uniform dosing interval tau) | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
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Inclusion criteria:
Exclusion criteria:
Significant pulmonary disease other than COPD 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 the any of the following:
Patients with any lung disease other than COPD (e.g. asthma, interstitial lung disease (ILD), cystic fibrosis, active tuberculosis, post-TB syndrome, clinically evident bronchiectasis, with a history of thoracotomy with pulmonary resection).
Patients with clinically relevant abnormal haematology, blood chemistry, or urinalysis at screening visit (Visit 1), if the abnormality defines a relevant disease as defined in exclusion criterion number 1.
All patients with a serum glutamate oxaloacetate transferase (SGOT) or serum glutamic pyruvic transaminase (SGPT) or total bilirubin higher than 1.5-fold ULN or serum creatinine higher than normal at Visit 1 (and at all repeated tests, if applicable) will be excluded regardless of the clinical condition. Laboratory evaluation can be repeated maximum two times.
A malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (patients with treated basal cell carcinoma are allowed).
Patients with current relevant psychiatric disorders based on the investigator´s judgement.
Patients with any respiratory infection (e.g. common cold, sinusitis, etc.) or COPD exacerbation within the six weeks prior to the screening visit (Visit 1) or between screening visit and randomization.
Patients with a history of two or more moderate or severe COPD exacerbations per year within the last two years.
Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion number 1.
Patients who are being treated with non-permitted concomitant medication.
Patients with a recent history (i.e. three years or less) of heart failure or patients with any cardiac arrhythmia requiring drug therapy.
Patients who have previously been randomised in this trial.
Current participation in another clinical trial (as defined in the ICH Harmonised Tripartite Guideline for Good Clinical Practice (GCP)).
Donation of more than 100 mL of blood within the past four weeks prior to screening.
A history of additional risk factors for torsade-de-pointes (e.g., heart failure, relevant hypokalemia, family history of Long QT Syndrome).
Pregnant or nursing women.
Gastrointestinal tract surgery that might affect absorption and elimination of drugs.
Patients with known hypersensitivity / allergy to the investigational medicinal product (IMP) or its excipients.
Male Patients who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until two months after study completion.
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boehringer Ingelheim Investigational Site | Berlin | Germany | ||||
| Boehringer Ingelheim Investigational Site |
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The trial consisted of 3 sequential dose groups of 28 patients each. Within each dose group, 21 patients received BI 113608 and 7 received placebo
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Oral administration of Placebo matching BI 113608 |
| FG001 | BI 113608 10 mg | Oral administration of BI 113608 10 mg film coated tablets twice daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo to BI 113608 low dose b.i.d. |
| Drug |
Film-coated tablet |
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| BI 113608 high dose b.i.d. | Drug | Film-coated tablet |
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| Placebo to BI 113608 medium dose b.i.d. | Drug | Film-coated tablet |
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| BI 113608 low dose b.i.d. | Drug | Film-coated tablet |
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| BI 113608 medium dose b.i.d. | Drug | Film-coated tablet |
|
| AUC Tau,ss | AUC tau,ss (area under the concentration-time curve of the BI 113608 in plasma at steady state over a uniform dosing interval tau) | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
| Tmax,ss | Tmax,ss (time from last dosing to maximum concentration of the BI 113608 in plasma at steady state) | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
| T1/2,ss | T1/2,ss (terminal half life of the BI 113608 in plasma at steady state) | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
| R(A,Cmax) | R(A,Cmax) (accumulation ratio of the BI 113608 in plasma at steady state after multiple oral administration over a uniform dosing interval tau, expressed as ratio of Cmax at steady state and after first dose) | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
| R(A,AUC) | R(A,AUC) (accumulation ratio of the BI 113608 in plasma at steady state after multiple oral administration over a uniform dosing interval tau, expressed as ratio of AUC at steady state and after first dose) | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
| Frankfurt |
| Germany |
| Boehringer Ingelheim Investigational Site | Gauting | Germany |
| Boehringer Ingelheim Investigational Site | Großhansdorf | Germany |
| Boehringer Ingelheim Investigational Site | Lübeck | Germany |
| Boehringer Ingelheim Investigational Site | Mannheim | Germany |
| FG002 | BI 113608 25 mg | Oral administration of BI 113608 25 mg film coated tablets twice daily |
| FG003 | BI 113608 50 mg | Oral administration of BI 113608 50 mg film coated tablets twice daily |
| COMPLETED |
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| NOT COMPLETED |
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Treated set: All patients who received at least 1 dose of study drug were included in the Treated Set (TS).
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Oral administration of Placebo matching BI 113608 |
| BG001 | BI 113608 10 mg | Oral administration of BI 113608 10 mg film coated tablets twice daily |
| BG002 | BI 113608 25 mg | Oral administration of BI 113608 25 mg film coated tablets twice daily |
| BG003 | BI 113608 50 mg | Oral administration of BI 113608 50 mg film coated tablets twice daily |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Gender | Count of Participants | Participants |
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| 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 | Number (%) of Patients With Drug-related Adverse Events (AEs) | Number (%) of patients with drug-related adverse events (AEs) | Treated set (TS) | Posted | Number | percentage of participants | AE's occuring upto end of treatment + 3 days follow up (Up to 31 days) |
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| Secondary | Cmax,ss | Cmax,ss (maximum measured concentration of BI 113608 in plasma at steady state over a uniform dosing interval tau) | Pharmacokinetic set (PKS): The patient set for the evaluation of PK endpoints included all evaluable patients in the treated set which provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of PK. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
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| Secondary | AUC Tau,ss | AUC tau,ss (area under the concentration-time curve of the BI 113608 in plasma at steady state over a uniform dosing interval tau) | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
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| Secondary | Tmax,ss | Tmax,ss (time from last dosing to maximum concentration of the BI 113608 in plasma at steady state) | PKS | Posted | Median | Full Range | hours | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
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| Secondary | T1/2,ss | T1/2,ss (terminal half life of the BI 113608 in plasma at steady state) | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
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| Secondary | R(A,Cmax) | R(A,Cmax) (accumulation ratio of the BI 113608 in plasma at steady state after multiple oral administration over a uniform dosing interval tau, expressed as ratio of Cmax at steady state and after first dose) | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
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| Secondary | R(A,AUC) | R(A,AUC) (accumulation ratio of the BI 113608 in plasma at steady state after multiple oral administration over a uniform dosing interval tau, expressed as ratio of AUC at steady state and after first dose) | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Pre-dose and 0:15(hours:min),0:30,0:45,1:00,1:30,2:00,3:00,4:00,6:00,9:00,11:45,71:45,167:45,611:45,623:45,635:45,647:45,648:15,648:30,648:45,649:00,649:30,650:00,651:00,652:00,654:00,657:00,660:00,672:00,696:00,720:00 hours after drug administration |
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From the first drug administration until 3 days after last study drug administration, up to 31 days.
The above mentioned time frame corresponds to AEs that occurred during on treatment period
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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 | Oral administration of Placebo matching BI 113608 | 1 | 21 | 11 | 21 | ||
| EG001 | 10 mg Bid | Oral administration of BI 113608 10 mg film coated tablets twice daily | 0 | 21 | 10 | 21 | ||
| EG002 | 25 mg Bid | Oral administration of BI 113608 25 mg film coated tablets twice daily | 0 | 21 | 13 | 21 | ||
| EG003 | 50 mg Bid | Oral administration of BI 113608 50 mg film coated tablets twice daily | 1 | 21 | 16 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | 17.0 | Systematic Assessment |
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| Blood potassium increased | Investigations | 17.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 17.0 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | 17.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | 17.0 | Systematic Assessment |
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| Headache | Nervous system disorders | 17.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
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| Sputum increased | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 17.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | 17.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | 17.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | 17.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | 17.0 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | 17.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | 17.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | 17.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | 17.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | 17.0 | 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 800-243-0127 | +1 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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