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

• Register: EUCTR
• Last refreshed on: 5 December 2016
• Main ID: EUCTR2013-004659-19-NL
• Date of registration: 27/02/2014
• Prospective Registration: Yes
• Primary sponsor: Bayer 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 2
• Date of first enrolment: 23/04/2014
• Target sample size: 492
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004659-19
• 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, Austria, Brazil, Bulgaria, China, Czech Republic, Germany, Hong Kong, Korea, Republic of, Latvia, Lithuania, Netherlands, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Taiwan, Thailand, Turkey, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1) Age at least 18 years;
2) 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
3) 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.
4) Stable pulmonary status as indicated by FEV1 (percent of predicted) >=30% and <90% (post-bronchodilator, if used as standard of treatment);
5) Stable regimen of standard treatment with:
o 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
o Macrolides if used as chronic treatment for BE for at least 6 months prior to screening.
6) Sputum production on the majority of days;
7) Ability to follow the inhaler device instructions;
8) Ability to complete questionnaires;
9) Written informed consent;
10) Negative urine pregnancy test result for women of childbearing potential before first dose of study drug;
11) 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 246
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 246

Exclusion criteria:
1) FEV1 <30% or >=90% predicted (post-bronchodilator);
2) Active allergic bronchopulmonary aspergillosis (ABPA);
3) Active and actively-treated non-tuberculosis mycobacterial (NTM) infection or tuberculosis;
4) Diagnosis of common variable immunodeficiency (CVID);
5) Recent significant hemoptysis (>=300 mL or requiring blood transfusion) in the preceding 4 weeks before screening (and during the screening period);
6) Primary diagnosis of COPD;
7) Known CF and / or documented chronic bronchial asthma;
8) Administration of any investigational drug within 4 weeks before screening;
9) Medical history of allergies to quinolones or fluoroquinolones;
10) Women who are pregnant, lactating, or in whom pregnancy cannot be excluded;
11) History of tendon disorders related to quinolone treatment;
12) History of myasthenia gravis;
13) Concomitant administration of tizanidine while on study drug;
14) Systemic or inhaled antibiotic treatment for any indication within 4 weeks prior to the administration of study drug; except for chronic macrolide use (see section 6.9).
15) Systemic corticosteroids at >10 mg/day prednisolone equivalent for >14 days within 4 weeks prior to the administration of study drug;
16) If participating in or has participated in other investigational interventional studies within the previous 4 weeks before screening;
17) 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
18) Previous assignment to treatment in this study (randomized in Study 15626); subjects who have participated in RESPIRE 1 will not be enrolled in RESPIRE 2.


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

Health Condition(s) or Problem(s) studied

non-CF bronchiectasis
MedDRA version: 19.0 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: 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, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Secondary Objective: The secondary objectives of this study are:
- To assess the frequency of pulmonary exacerbations in subjects with non–CF BE. For this secondary exacerbation events are defined as events with systemic antibiotic use and worsening of at least one sign/symptom ;
- To assess pathogen eradication and acquisition of new pathogenic organisms not present at baseline;
- To assess the safety and tolerability of different long term regimens of ciprofloxacin DPI;
- To assess the improvement of quality of life by Saint George’s Respiratory Questionnaire;
- To assess the improvement of quality of life by Quality of Life-Bronchiectasis (QOL–B) questionnaire’s respiratory symptom domain;
- To assess changes in lung function as measured by change in FEV1.

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

Main Objective: The primary objectives of this 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 within 48 weeks after start of treatment (as agreed with the US FDA [Food and Drug Administration]).
- 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 BE (as agreed with the EMA/CHMP and Japan PMDA) within 48 weeks after start of treatment (wording harmonized with amendment no.2).

Primary end point(s): The primary efficacy variables of this study are time to first pulmonary exacerbation requiring an intervention with systemic antibiotics within 48 weeks after start of treatment (for US NDA[New Drug Application]), 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 Outcome(s)

Timepoint(s) of evaluation of this end point: Confirmatory analyses for pathogen eradication, occurrence of new pathogens and lung function, SGRQ and QoL-B will be evaluated at end of the on-treatment part of the 6th cycle for subjects in the 28 day on/off regimen, at end of the on-treatment part of the 12th cycle for subjects in the 14 day on/off regimen. Frequency of exacerbations (US NDA) / Time to first exacerbation (EU MAA) will be evaluated over 48 weeks.

Secondary end point(s): The secondary objectives of this study are:
• To assess frequency of exacerbations over 48 weeks (US NDA) / time to first exacerbation within 48 weeks after start of treatment (EU MAA);
• To assess frequency of pulmonary exacerbation in subjects with non–CF BE. For this secondary endpoint exacerbation events are defined as events with systemic antibiotic use and worsening of at least one sign/symptom;
• To assess pathogen eradication and acquisition of new pathogenic organisms not present at baseline;
• To assess the safety and tolerability of different long term regimens of ciprofloxacin DPI;
• To assess the improvement of quality of life by Saint George’s Respiratory Questionnaire;
• To assess the improvement of quality of life by Quality of Life respiratory symptom domain Questionnaire (QoL-B);
• To assess changes in lung function as measured by changes in forced expiratory volume in 1 second (FEV1).

Secondary ID(s)

2013-004659-19-DE

BAYQ3939/15626

Source(s) of Monetary Support

Bayer AG