E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
bronchiectasis: localized, irreversible dilation of part of the bronchial tree |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006445 |
E.1.2 | Term | Bronchiectasis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetics will be assessed on blood and sputum samples collected at baseline and at one other study visit, for a subset of subjects at selected sites. The subject will be asked to produce one to two sputum samples. Sampling should start after the administration of the study drug, with the first sample ideally approximately 2-4 h after the end of inhalation. All records identifying the patient will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. Rationale and procedures of Pharmacokinetics are described in the Pharmacokinetic Sampling Manual version 3.0 dated 13/Sep/2012 |
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E.3 | Principal inclusion criteria |
Age >18 years;
Proven and documented diagnosis of non-CF idiopathic or post-infectious BE by both:
HRCT scan including 2 or more lobes and dilated airways compatible with BE at initial diagnosis;
and
Positive culture from an adequate sputum sample for Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Stenotrophomonas maltophilia or Burkholderia cepacia 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. |
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E.4 | Principal 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 disease and other 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; Previous assignment to treatment in this study (randomized in Study 15625). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first exacerbation
Description: Exacerbation is defined by signs and symptoms plus intervention with systemic antibiotics
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
over 48 weeks after baseline |
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E.5.2 | Secondary end point(s) |
- Mean number of exacerbations per patient per 48 weeks
- Pathogens present at baseline and eradicated at 48 weeks
- Changes of Saint George’s Respiratory Questionnaire (SGRQ) score from baseline to 48 weeks
- New pathogens at 48 weeks, not present at baseline
- Changes of forced expiratory volume in 1 second (FEV1) from baseline to 48 weeks
- Number of participants with adverse events as a measure of safety and tolerability |
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E.5.2.1 | 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
- over 56 weeks after screening
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Denmark |
France |
Germany |
Israel |
Italy |
Japan |
New Zealand |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |