Safety and Efficacy of Oral BAY 85-8501 in Patients with inflammation of the tubes in the lungs.

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2012-004491-18-GB
• Date of registration: 18/12/2012
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: Safety and Efficacy of Oral BAY 85-8501 in Patients with inflammation of the tubes in the lungs.
• Scientific title: A Phase IIa, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety and Efficacy of 28 Day Oral Administration of BAY 85-8501 in Patients with non-Cystic Fibrosis Bronchiectasis
• Date of first enrolment: 30/01/2013
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004491-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy, Spain, United Kingdom

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer Healthcare AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer Healthcare AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent
2. Age =18 years
3. Proven and documented diagnosis of non-CF idiopathic or post-infectious BE by HRCT scan including 2 or more lobes and dilated airways compatible with BE at initial diagnosis
4. Stable pulmonary status as indicated by FEV1 percent predicted =30%and <90% (post-bronchodilator)
5. If subjects are on a pulmonary training program, they must: 1) have been stable on the program for the 4 weeks prior to screening, and 2) continue the pulmonary training program throughout the entire study period
6. Stable (i.e., no dose change) regimen of standard BE treatments, including treatment with hypertonic solutions, mucolytics, long-acting and short-acting ß2-agonists and anticholinergic agents, inhaled corticosteroids, low dose systemic corticosteroids (=10 mg/day prednisone equivalent) and regular physiotherapy for at least 4 weeks prior to screening. Low dose macrolides (as anti-inflammatory therapy) should be administered for at least 6 months prior to screening if used as chronic treatment for BE. These treatments are hereafter referred to as ‘standard BE treatment’
7. Spontaneous sputum sample, assessed as purulent, per investigator judgement
8. Cough and sputum production on most days. Subject must be able to produce an induced sputum sample at screening, which will be used for baseline biomarker assessment
9. Ability to complete questionnaires
10. Negative urine pregnancy test result for women of non-childbearing potential (WONCBP) before first dose of study drug
11. Women of non-childbearing potential, defined as postmenopausal women, or permanently sterilized women (bilateral tubal ligation, bilateral ovariectomy, or hysterectomy. Women of childbearing potential (WOCBP) will not be entered into the study. Post-menopause is defined as having had no menses in the past 12 months,
or
Male subjects, with partners of childbearing potential, should use at least two forms of highly effective contraceptive methods, unless they agree to abstain from heterosexual intercourse while participating in the study. Highly effective contraception methods are the following: consistent use of oral, injected or implanted methods of contraception, intra-uterine device or intra-uterine system, barrier methods (condom, diaphragm, cervical cap) when used with spermicidal foam/gel/film/cream. Sterilized male participants will also need to use an additional contraception form. One (for sterilized males) or two (for non-sterilized males) of the following methods should be used during the study and continue for 3 months after the last follow-up visit
a) Barrier methods of contraception (e.g., condom or occlusive cap (diaphragm or cervical/vault caps). The use of barrier contraceptives should always be supplemented with spermicidal foam/gel/film/cream/suppository
b) Double-barrier methods of contraception (e.g., condom and occlusive cap with spermicidal foam/gel/film/cream/suppository)
c) Intrauterine contraceptive device
d) Approved pharmaceutical contraceptive product (e.g., birth control pills or patches, long-term injectable or implantable hormonal contraceptive).

Are the trial subjects under 18? no
Num
Exclusion criteria:
1. FEV1 <30% or =90% predicted (post-bronchodilator)
2. Pre-bronchodilator FEV1: difference between Screening (Visit 1) and Baseline (Visit 2) is =20%
3. Recent significant hemoptysis (=300 mL or requiring blood transfusion) in the preceding 4 weeks before screening (and during the screening period)
4. Known cystic fibrosis and/or documented chronic bronchial asthma
5. Active allergic bronchopulmonary aspergillosis (ABPA)
6. Diagnosis of common variable immunodeficiency (CVID)
7. Systemic or inhaled antibiotic treatment within 4 weeks prior to screening
8. Treatment of an exacerbation within 4 weeks prior to screening
9. Treatment with immunomodulatory agents, within 8 weeks prior to screening and throughout the study (macrolides will be allowed to be used in the study, per conditions defined in Inclusion criteria #6)
10. Systemic corticosteroids at >10 mg/day prednisolone equivalent for >2 weeks within 4 weeks prior to screening
11. Treatment with moderate and strong Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors within 1 week prior to screening (e.g., clarithromycin, erythromycin, telithromycin, ciprofloxacin, itraconazole, ketoconazole, voriconazole, posaconazole, fluconazole, grapefruit juice) (Note: this list is not all-inclusive, and investigator is referred to FDA website: [http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#potency])
12. Treatment with moderate and strong CYP3A4 inducers within 2 weeks prior to screening (e.g., St. John’s Wort, rifampin, carbamazepine, phenytoin) (Note: this list is not all-inclusive, and investigator is referred to FDA website: [http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#potency])
13. Administration of any investigational drug within 4 weeks before screening
14. Previous assignment to treatment during this study
15. Women of childbearing potential (WOCBP). Women who are pregnant, lactating, or in whom pregnancy cannot be excluded. Peri-menopausal women are excluded from participating in the protocol
16. Subjects with a medical disorder, condition, or history of such that would impair the subject’s ability to participate or complete this study in the opinion of the investigator
17. Subjects with a history of severe allergies or multiple drug allergies
18. Subjects with hypersensitivity to the study drug or any of the excipients
19. Subjects with a history of hypertonic saline intolerance
20. Affiliation with personnel at the investigational site (e.g., a close friend or relative of the investigator, employee or student at the site).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-Cystic Fibrosis Bronchiectasis
MedDRA version: 15.1 Level: PT Classification code 10006445 Term: Bronchiectasis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: BAY 85-8501
Product Code: BAY 85-8501
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: BAY 85-8501
Other descriptive name: BAY 85-8501
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To assess the safety and tolerability of 28 day oral administration of BAY 85-8501 versus placebo in subjects with non-CF Bronchiectasis (BE)

Secondary Objective: To examine the effect of BAY 85-8501 on pulmonary function, biomarkers of inflammation and tissue damage, and the impact on overall health and perceived well-being.

To evaluate the pharmacokinetics of BAY 85-8501

Primary end point(s): Safety variables measured during the treatment and follow-up period and include physical exam, vital signs, 12-lead ECG, safety lab assessments (hematology, chemistry and urinalysis), and AEs, including SAEs.

Timepoint(s) of evaluation of this end point: 8 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 8 weeks

Secondary end point(s): 1) Efficacy variables which are the changes from baseline by treatment in:
Pulmonary function tests (FEV1, FVC, FEF25-75)
SGRQ
Sputum weight
Biomarkers
Sputum
Blood
Urine

2. Pharmacokinetic variables: plasma concentrations at different time points

Secondary ID(s)

BAY85-8501-16359

Source(s) of Monetary Support

BAYER HEALTHCARE AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 24/07/2015
• Date Completed: 13/06/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004491-18/results