Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis (non–CF BE)

• Register: EUCTR
• Last refreshed on: 13 June 2016
• Main ID: EUCTR2011-004208-39-SK
• Date of registration: 21/10/2014
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis (non–CF BE)
• Scientific title: Randomized, double-blind, placebo-controlled, multicEnter Study comParing CIprofloxacin DPI 32.5 mg BID intermittently administered for 28 days on / 28 days off or 14 days on / 14 days off versus placebo to evaluate the time to fiRst pulmonary exacErbation and frequency of exacerbations in subjects with non–cystic fibrosis bronchiectasis. - RESPIRE 1
• Date of first enrolment: 18/11/2014
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004208-39
• 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: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Denmark, France, Germany, Israel, Italy, Japan, Latvia, New Zealand, Serbia, Slovakia, Spain, United Kingdom, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
? Age >18 years;
? Proven and documented diagnosis of non CF idiopathic or post infectious BE by CT scan (conventional high resolution CT is considered the standard) including 2 or more lobes and dilated airways compatible with BE at initial diagnosis
? Positive culture from an adequate sputum sample for Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Stenotrophomonas maltophilia or Burkholderia cepacia obtained at screening and with history =2 documented exacerbations in the past 12 months;
? Stable pulmonary status as indicated by FEV1 (percent of predicted) >=30% and <90% (post-bronchodilator, if used as standard of treatment);
? Stable regimen of standard treatment with:
- Bronchodilators, anticholinergics, inhaled corticosteroids, or mucolytics, if used as chronic treatment for BE, at least for the past 4 weeks prior to screening;
Subjects on maintenance therapy with low-dose systemic corticosteroids should be receiving <=10 mg/day prednisolone equivalent at least for the past 4 weeks before the screening visit;
and/or
- Macrolides if used as chronic treatment for BE for at least 6 months prior to screening;
? Sputum production on the majority of days;
? Ability to follow the inhaler device instructions;
? Ability to complete questionnaires;
? Written informed consent;
? Negative urine pregnancy test result for women of childbearing potential before first dose of study drug;
? Women of childbearing potential and men must agree to use adequate contraception when sexually active. This applies from the time of signing of the informed consent form (ICF) until 3 months after the last study drug administration. Adequate methods of contraception include vasectomy, or condom use, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization, or oral contraceptives.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion criteria:
? FEV1 <30% or >=90% predicted (post-bronchodilator);
? Active allergic bronchopulmonary aspergillosis (ABPA);
? Active and actively-treated non-tuberculosis mycobacterial (NTM) infection or tuberculosis;
? Diagnosis of common variable immunodeficiency (CVID);
? Recent significant hemoptysis (>=300 mL or requiring blood transfusion) in the preceding 4 weeks before screening (and during the screening period);
? Primary diagnosis of COPD;
? Known CF and / or documented chronic bronchial asthma;
? Administration of any investigational drug within 4 weeks before screening;
? Medical history of allergies to quinolones or fluoroquinolones;
? Women who are pregnant, lactating, or in whom pregnancy cannot be excluded;
? History of tendon disorders related to quinolone treatment;
? History of myasthenia gravis;
? Concomitant administration of tizanidine while on study drug;
? Systemic or inhaled antibiotic treatment for any indication within 4 weeks prior to the administration of study drug; except for chronic macrolide use;
? Systemic corticosteroids at >10 mg/day prednisolone equivalent for >14 days within 4 weeks prior to the administration of study drug;
? If participating in or has participated in other investigational interventional studies within the previous 28 days
? Subjects with any other conditions (specifically those which are addressed in the warnings and precautions section of the IB) or clinically relevant laboratory findings that the investigator defines as not appropriate for enrollment of a subject into the study
? Previous assignment to treatment in this study (randomized in Study 15625).


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

Health Condition(s) or Problem(s) studied

bronchiectasis
MedDRA version: 18.1 Level: PT Classification code 10006445 Term: Bronchiectasis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

Intervention(s)

Product Name: Ciprofloxacin DPI
Product Code: BAYq3939
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Ciprofloxacin
Current Sponsor code: BAYq3939
Other descriptive name: CIPROFLOXACIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 32.5-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: over 48 weeks after baseline

Main Objective: The primary objectives of the study are:
• To evaluate the efficacy of ciprofloxacin DPI administered BID intermittently for 28 days on study treatment / 28 days off study treatment or 14 days on study treatment / 14 days off study treatment to prolong the time to first exacerbation requiring an intervention with systemic antibiotics in subjects with non CF BE.
•To evaluate the efficacy of ciprofloxacin dry powder for inhalation (DPI) administered 2 times a day (BID) intermittently for 28 days on study treatment / 28 days off study treatment or 14 days on study treatment / 14 days off study treatment in reducing the frequency of pulmonary exacerbation requiring an intervention with systemic antibiotics in subjects with non–CF BEwithin 48 weeks after start of treatment.

Primary end point(s): The primary efficacy variables of this study are time to first pulmonary exacerbation requiring an intervention with systemic antibiotics (for US NDA), and frequency of exacerbations requiring an intervention with systemic antibiotics during the 48 weeks treatment phase (for EU MAA and further ex-US registrations).

Secondary Objective: The secondary objectives of this study are:
•To assess pathogen eradication and acquisition of new pathogenic organisms not present at baseline;
•To assess the safety and tolerability of different long term regimen of ciprofloxacin DPI;
•To assess the improvement of quality of life by Saint George’s Respiratory Questionnaire (SGRQ);
•To assess changes in lung function as measured by change in FEV1.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: respectively:
- over 48 weeks after baseline
- baseline and 48 weeks
- baseline and 48 weeks
- baseline and 48 weeks
- baseline and 48 weeks
- baseline and 48 weeks
- up to 58 weeks after screening

Secondary end point(s): -Changes from baseline in the disease-specific PRO score QOL-B respiratory symptom domain;
-Number/time to exacerbation using different definitions of exacerbation;
-Changes from baseline in FVC and FEV1 / FVC (post- bronchodilator spirometry);
-Changes from baseline in inflammatory markers (hsCRP, PMN count);
-Exploratory endpoint (at participating centers): Changes from baseline in sputum inflammatory markers IL 8 and MPO;
-Shift in minimal inhibitory concentration (MIC) over time;
-Number of participants with adverse events as a measure of safety and tolerability

Secondary ID(s)

BAYq3939/15625

2011-004208-39-DE

Source(s) of Monetary Support

Bayer HealthCare AG