Safety, Tolerability and Pharmacokinetics and Effect on Inflammation of Oral BI 1026706 in Patients With COPD

Study Overview
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Brief Summary
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The main objective of the current trial is to investigate safety, tolerability, pharmacokinetics and effect on inflammation of oral BI 1026706 administered twice daily for 4 weeks in patients with COPD.

Official Title
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A Phase I Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of BI 1026706 Administered Orally as Tablets Twice Daily for 4 Weeks to Patients With COPD in Order to Evaluate Safety, Tolerability, Pharmacokinetics and Effect on Inflammation

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: BI 1026706
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed informed consent consistent with ICH-Good Clinical Practice (GCP) guidelines and local legislation prior to participation in the trial. Medication washout and medication restrictions are allowed only after signed informed consent is obtained. Males or females not of childbearing potential between 40 and 80 years (each inclusive) of age, on the day of patient´s signature of informed consent. All patients must have a documented diagnosis of COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD). Post-bronchodilator forced expiratory volume (FEV)1 of >=40% and <=90% of predicted normal at Visit 1 Post-bronchodilator FEV1/forced vital capacity (FVC) <70% at Visit 1 Patients must be current or ex-smokers with a smoking history of more than 10 pack years Patients on stable respiratory medications for at least 6 weeks prior to randomization (Visit 3). Patients must be able to perform technically acceptable pulmonary function tests. 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: Put the patient at risk because of participation in the study Influence the results of the study Cast doubt on the patients ability to participate in the study Patients with current asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma. Patients with clinically relevant abnormal hematology, blood chemistry, or urinalysis at the screening visit (Visit 1), if the abnormality indicates a relevant disease as defined in exclusion criterion number 1. Safety laboratory screening evaluation (Visit 1) can be repeated a maximum of two times. Patients with a history of myocardial infarction or apoplexy within 6 months of the screening visit (Visit 1) or between the screening visit (Visit 1) and randomization. Patients with a history of and/or active life-threatening cardiac arrhythmia, as assessed by the investigator. Patients with a marked baseline prolongation of QT/QTcB interval (such as repeated demonstration of a QTcB interval >450 ms), pulse/heart rate outside 50 to 90 bpm at Visit 1 (if confirmed by pulse rate measurement over 60 seconds), or any other relevant ECG finding. Patients with a history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome). Patients with known active tuberculosis. Patients with clinically relevant bronchiectasis, as assessed by the investigator. Patients with any respiratory infection (such as common cold, acute sinusitis, or similar illnesses) or COPD exacerbation within 6 weeks prior to the screening visit (Visit 1) or between the screening visit and randomization. Patients who have undergone thoracotomy with pulmonary resection (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1). Patients with a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last 5 years. Patients with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed to participate. Patients with a history of and/or active significant alcohol or drug abuse as assessed by the investigator. Patients who are being treated with non-permitted concomitant medication. Patients who have taken an investigational drug within 4 weeks prior to Visit 1 or if screening occurs within six half-lives of intake of another investigational drug (whichever is greater). Patients with surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication as assessed by the investigator. Patients with veins unsuited for venipuncture (for instance, veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture) as assessed by the investigator. Patients who are unable to comply with the dietary regimen. Patients who have been previously randomized in this study. Patients who have donated more than 100 mL blood in the 4 weeks prior to Visit 1 and between Visit 1 and Visit 3 or patients who have the intention to donate blood between Visit 3 and four weeks after the end of trial visit. Patients who are pregnant or breastfeeding Male patients 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. Patient is assessed as unsuitable for inclusion by the investigator; for instance, because he or she is not considered to comply with study requirements

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 1026706 low dose<br> | Drug: BI 1026706<br> <br> Drug: Placebo<br>* For blinding purposes<br>|
| Experimental: BI 1026706 medium<br> | Drug: BI 1026706<br> <br> Drug: Placebo<br>* For blinding purposes<br>|
| Experimental: BI 1026706 high dose<br> | Drug: BI 1026706<br> <br> Drug: Placebo<br>* For blinding purposes<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> Drug: Placebo<br>* For blinding purposes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of BI 1026706, as Assessed by Frequency (in Percent) of Patients With Treatment Emergent Adverse Events (TEAEs) Over the Treatment Period. | Safety and tolerability of BI 1026706, as assessed by frequency (in percent) of patients with treatment-emergent adverse events (TEAEs) over the treatment period. | From first drug administration until 4 days after last drug administration, up to 32 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Absolute Number of Neutrophil in Sputum at the End of the Planned Treatment Period | Change in Absolute Number of Neutrophil in Sputum at the end of the planned treatment period | 28 days | 
| Maximum Measured Concentration of BI 1026706 in Plasma (Cmax) After the First Dose (Morning of Day 1) | Maximum measured concentration of BI 1026706 in plasma (Cmax) after the first dose (morning of Day 1) | -0:10 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, and 12:00h after drug administration. | 
| Time From Dosing to Maximum Concentration of BI 1026706 in Plasma (Tmax) After the First Dose (Morning of Day 1) | Time from dosing to maximum concentration of BI 1026706 in plasma (Tmax) after the first dose (morning of Day 1) | -0:10 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, and 12:00h after drug administration. | 
| Area Under the Concentration-time Curve of BI 1026706 in Plasma (AUC 0-12h) After the First Dose (Morning of Day 1) | Area under the concentration-time curve of BI 1026706 in plasma (AUC 0-12h) after the first dose (morning of Day 1) | -0:10 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, and 12:00h after drug administration. | 
| Maximum Measured Concentration of BI 1026706 in Plasma at Steady State Over a Uniform Dosing Interval Tau (Cmax, ss) After the Last Dose (Morning of Day 28) | Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval tau (Cmax, ss) after the last dose (morning of Day 28) | -0:10 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, and 12:00h after drug administration. | 
| Time From Dosing to Maximum Concentration of BI 1026706 in Plasma (Tmax, ss) After the Last Dose (Morning of Day 28) | Time from dosing to maximum concentration of BI 1026706 in plasma (Tmax, ss) after the last dose (morning of Day 28) | -0:10 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, and 12:00h after drug administration. | 
| Area Under the Concentration-time Curve of BI 1026706 in Plasma at Steady State Over a Uniform Dosing Interval Tau (AUC Tau, ss) After the Last Dose (Morning of Day 28) | Area under the concentration-time curve of BI 1026706 in plasma at steady state over a uniform dosing interval tau (AUC tau, ss) after the last dose (morning of Day 28) | -0:10 hour(h) before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, and 12:00h after drug administration. |