Bronchiectasis
Conditions
Keywords
Elastase Inhibition
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.
Interventions
DRUGBAY85-8501
BAY85-8501 (1.0 mg, 2 tablets each 0.5 mg) will be administered orally once daily in the morning
DRUGPlacebo
Placebo (1.0 mg, 2 tablets each 0.5 mg) will be administered orally once daily in the morning
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 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 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 |
| 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 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 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 |
Countries
France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed