E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011763 |
E.1.2 | Term | Cystic fibrosis lung |
|
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 objective is to compare the change in FEV1 from baseline to Day 28-30 between Cipro Inhale-treated and placebo-treated subjects after a 4-week treatment period |
|
E.2.2 | Secondary objectives of the trial |
•To compare the change in FEV1 from baseline to Visits 4, 5, and Follow-up Visits 8 and 9 between the different treatment groups (Cipro Inhale 50 mg (32.5 mg) BID, Cipro Inhale 75 mg (48.75 mg) BID, and placebo) •Assess the change in P aeruginosa density in the sputum from baseline between the different treatment groups at Visits 4, 5, 7, 8 and 9 •Determine the time to first pulmonary exacerbation requiring any antipseudomonal intervention or hospitalization occurring in subjects given different doses of Cipro Inhale compared to subjects given placebo •Assess the change from baseline forced vital capacity (FVC) and forced expiratory flow rate (FEF) 25-75% of the different treatment groups at Visits 4, 5, 7, 8 and 9 •Assess the occurrence of drug-induced bronchospasm in subjects given different doses of Cipro Inhale compared to placebo •Assess the safety profile of subjects given different doses of Cipro Inhale compared to placebo Refer to Protocol for further secondary objectives |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subjects, or their legal representative(s), must have given their written informed consent to participate in the study after receiving adequate previous information and prior to any study specific procedures •Children (12 – 17 years) or adults ≥18 years •Documented diagnosis of CF: -documented sweat chloride ≥60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) or nasal potential difference -or either homozygous for ΔF508 genetic mutation or a compound heterozygous for 2 known CF mutations -and clinical findings consistent with CF •Chronic colonization with P aeruginosa defined as a positive respiratory tract culture (sputum or throat swab) within 12 months prior to screening and at screening (Note: subjects with negative culture at screening can, at the discretion of the investigator, be rescreened at a later date) •Ability to perform reproducible pulmonary function tests •Ability to produce sputum (noninduced) •Stable pulmonary status, FEV1 ≥35% to ≤75% (intraindividual variability ±10% of absolute value). Note: The subject is not eligible for enrollment if the variability results in (or leads to) an FEV1 <35%. •Room air oximetry ≥88% saturation •Off antibiotics (except macrolide) and Cipro (oral) for at least 30 days prior to the administration of study drug for pulmonary exacerbation. Non-antipseudomonal antibiotics administered for other indications are allowed. •Stable regimen of standard CF treatment including chest physiotherapies and exercise regimens should not change during the 30 days prior to the administration of study drug and during the study (including macrolide administration unchanged in the previous 30 days) •Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period •Women who are willing to use an adequate method of contraception for 3 months after receiving the study drug. Adequate methods of contraception include vasectomy or condom use by their partners, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization or oral contraceptive. |
|
E.4 | Principal exclusion criteria |
•Findings on screening history and physical examination unrelated to CF that could potentially affect the efficacy measurements (eg, chest surgery) •Subjects with colonization of P aeruginosa and a CIPRO MIC of ≥256 µg/ml or mg/l •Burkholderia cepacia complex colonization of their respiratory tract within the past 12 months (documented by screen laboratory) •Known aspergillosis (unless asymptomatic). Patients with invasive disease, ABPA with IgE > 500 mg/dL will be excluded. •Transaminase level >3x upper limit of normal (ULN) •Massive hemoptysis (≥300 cc or requiring blood transfusion) in the preceding 4 weeks •IV antibiotic treatment for pulmonary exacerbation in the past 30 days prior to the first study drug administration •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 or the sponsor •Febrile illness within 1 week before the start of the study •Active treatment for nontuberculosis mycobacteria •Exposure to any investigational drug within 30 days •Any history of allergic reaction to fluoroquinolones or other quinolones •On oral steroids >20 mg/day for longer than 14 days in the past 3 months •Creatinine ≥2x ULN •Subjects with a history of severe allergies, severe non-allergic drug reactions, or severe multiple drug allergies (i.e. severe allergies to multiple classes of drugs or multiple drug regardless of class) •Female subjects who are pregnant, lactating or in whom pregnancy cannot be excluded (Note: a urine pregnancy test will be performed on all women of childbearing potential before inclusion in the study, followed by serum pregnancy test.) •Patients < 18 years of age with a history of arthropathy related to quinolone treatment •Patients < 18 years of age with chronic musculoskeletal disease (eg, juvenile rheumatoid arthritis) •Patients < 18 years of age with an underlying chronic illness if high risk for chronic or recurrent arthritis or tendonitis (eg, inflammatory bowel disease; Note: pediatric patients with CF associated arthritis [CFAA] or hypertrophy pulmonary osteoarthritis [HPOA] should not be enrolled) •Patients < 18 years of age with an abnormal musculoskeletal evaluation at baseline |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To compare the change in FEV1 between Cipro Inhale-treated and placebo-treated subjects after a 4-week treatment period |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | Information not present in EudraCT |
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 |
|
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
|
End of trial is the last subject last visit |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |