Safety and Efficacy of Oral BAY85-8501 in Patients With Non-CF (Cystic Fibrosis) Bronchiectasis

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to assess the safety and tolerability of 28 day oral administration of BAY85-8501 versus placebo in subjects with non-CF Bronchiectasis (BE). The secondary objectives are to examine the effect of BAY85-8501 on pulmonary function, biomarkers of inflammation and tissue damage, and the impact on overall health and perceived well-being and to evaluate the pharmacokinetics of BAY85-8501.

Official Title
-----------------
A Phase IIa, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety and Efficacy of 28 Day Oral Administration of BAY85-8501 in Patients With Non-Cystic Fibrosis Bronchiectasis

Conditions
-----------------
Bronchiectasis

Intervention / Treatment
-----------------
* Drug: BAY85-8501
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Proven and documented diagnosis of non-CF (cystic fibrosis) idiopathic or post-infectious BE (bronchiectasis) by computed tomography (CT) scan [conventional high resolution CT is considered the standard], including 2 or more lobes and dilated airways compatible with BE at initial diagnosis Stable pulmonary status as indicated by the forced, expired volume in 1 second (FEV1) percent predicted ≥30% and <90% (post-bronchodilator) Stable (i.e., no dose change) regimen of standard BE treatment administered at least for 4 weeks prior to screening Cough on most days Exclusion Criteria: Forced, expired volume in 1 second <30% or ≥90% predicted (post-bronchodilator) Recent significant hemoptysis (≥300 mL or requiring blood transfusion) in the preceding 4 weeks before screening (and during the screening period) Known cystic fibrosis and/or documented chronic bronchial asthma Active allergic bronchopulmonary aspergillosis (ABPA) Diagnosis of common variable immunodeficiency (CVID) Systemic or inhaled antibiotic treatment within 4 weeks prior to screening Treatment of an exacerbation within 4 weeks prior to screening Systemic corticosteroids at >10 mg/day prednisolone equivalent for >2 weeks within 4 weeks prior to screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY85-8501<br> | Drug: BAY85-8501<br>* BAY85-8501 (1.0 mg, 2 tablets each 0.5 mg) will be administered orally once daily in the morning<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo (1.0 mg, 2 tablets each 0.5 mg) will be administered orally once daily in the morning<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Subjects Who Need To Discontinue Study Medication Due To Findings In Physical Examination |  | From start of study treatment up to follow up visit (28 days after last dose) | 
| Change From Baseline in Systolic Blood Pressure At Days 7, 14, 21, 28, 56 |  | Baseline (Day 1), Day 7, 14, 21, 28, 56 | 
| Change From Baseline in Diastolic Blood Pressure At Days 7, 14, 21, 28, 56 |  | Baseline (Day 1), Day 7, 14, 21, 28, 56 | 
| Change From Baseline in Heart Rate At Days 7, 14, 21, 28, 56 |  | Baseline (Day 1), Day 7, 14, 21, 28, 56 | 
| Number of Subjects With new Abnormal (Pathologic) Electrocardiogram (ECG) Findings From Baseline to Day 28 |  | Baseline (Day 1), Day 7, 14, 21, 28 | 
| Number of Subjects who Show Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Total Bilirubin (TB) Abnormalities in Their Safety Lab Assessment |  | Baseline (Day 1), Day 7, 14, 21, 28, 56 | 
| Number of Subjects With Drug Related Adverse Events as a Measure of Safety And Tolerability |  | Baseline (Day 1), Day 7, 14, 21, 28, 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pulmonary Function Test Forced Expired Volume in 1 Second (FEV1) At Days 7, 14, 21, 28, 56 |  | Baseline (Day 1), Day 7, 14, 21, 28, 56 | 
| Change From Baseline in Pulmonary Function Test Forced Vital Capacity (FVC) at Days 7, 14, 21, 28, 56 |  | Baseline (Day 1), Day 7, 14, 21, 28, 56 | 
| Change From Baseline in Pulmonary Function Test Forced Expiratory Flow Over the Middle Half of Subject's Forced Vital Capacity (FVC) (FEF2575) at Days 7, 14, 21, 28, 56 |  | Baseline (Day 1), Day 7, 14, 21, 28, 56 | 
| Change From Baseline in Total Score on St. George's Respiratory Questionnaire (SGRQ) at Day 28 and 56 |  | Baseline (Day 1), Day 28 and 56 | 
| Change From Baseline in 24 Hours Sputum Weight at Day 28 |  | Baseline (Day 1), Day 28 | 
| Change From Baseline of Biomarkers in Sputum at Days 14, 28, 56: Alpha1 Antitrypsin Human Neutrophil Elastase (A1AHNE) Complex, Interleukin-8(IL-8) |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Biomarkers in Sputum at Days 14, 28, 56: Neutrophil cell Count |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Human Neutrophil Elastase (NE) Activity in Sputum at Days 14, 28, 56 |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Human Neutrophil Elastase (NE) Concentration in Sputum at Days 14, 28, 56 |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Biomarkers in Blood at Days 14, 28, 56: C-reactive Protein |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Biomarkers in Blood at Days 14, 28, 56: Interleukin-8 (IL8) |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Biomarkers in Blood at Days 14, 28, 56: Neutrophil cell Count |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Biomarkers in Urine At Days 14, 28, 56: Creatinine |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Biomarkers in Urine at Days 14, 28, 56: Desmosine |  | Baseline (Day 1), Day 14, 28 and 56 | 
| Change From Baseline of Biomarkers in Urine at Days 14, 28, 56: Normalized Desmosine Value to Creatinine |  | Baseline (Day 1), Day 14, 28 and 56 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Elastase Inhibition