E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-cystic fibrosis bronchiectasis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006446 |
E.1.2 | Term | Bronchiectasis NOS |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether the microbiological efficacy of Ciprofloxacin for Inhalation (CFI) 100 mg and 150 mg are superior to placebo (Control Liposomes for Inhalation [CLI]) in the treatment of patients with non cystic fibrosis (CF) bronchiectasis by evaluating changes in P. aeruginosa log10 colony-forming units (CFU)/gram of sputum. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study will include comparison of CFI 100 mg and 150 mg to placebo (CLI) with respect to the following: 1. Microbiological efficacy 2. Time to, number of, severity of, and time to resolve exacerbations 3. Changes in spirometry 4. Quality of life (QOL) 5. Safety and tolerability
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Males or females at least 18 years of age, who are able to walk. 2.Have had a confirmed diagnosis of non-CF bronchiectasis per computed tomography. 3.Confirmed history of at least one exacerbation treated with a course of antibiotics within the last 12 months. 4.Have been off any anti-pseudomonal antibiotic for a minimum of 28 days prior to Day 1 (Visit 1). 5.Have FEV1 of more than 25% of predicted values at the Screening Visit (Visit 0). 6.Have positive documented P. aeruginosa in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 12 months prior to the Screening Visit (Visit 0) and in the sputum/ deep-throat cough swab culture collected at the Screening Visit (Visit 0). 7.Are clinically stable in the opinion of the investigator. 8.Are willing to comply with the requirements for participation in the study. 9.Are willing to use an acceptable method of contraception during the study. 10.Female patients of childbearing potential must provide a negative pregnancy test at the Screening Visit and must use an acceptable method of contraception for at least 3 weeks prior to the first dose of study drug and for 30 days after the last dose of study drug. Acceptable methods of contraception for women are orally administered hormonal contraceptives, surgical intervention, intrauterine device (IUD), and sexual abstinence. If a hormonal contraceptive is utilized as the method of contraception, the same method must have been used for at least 3 months prior to Visit 1. To be considered “not of child bearing potential”, female patients must be at least 2 years postmenopausal, or have been irreversibly surgically sterilized by hysterectomy, oophorectomy, or bilateral tubal ligation for at least 3 months prior to the first dose of study drug. Male patients whose female partners are of child bearing potential (definition as above) must agree to use an acceptable method of birth control (as listed above) for the duration of study treatment and for 30 days after the last dose of study drug. 11.Patients who meet all inclusion and none of the exclusion criteria and meet the following sputum criteria at screening will be enrolled into the study: • Sputum P. aeruginosa density ≥6 log10 CFU/gram • Sputum P. aeruginosa sensitive to ciprofloxacin If a patient’s initial sputum sample does not meet the above criteria for density and sensitivity, the patient will be allowed a maximum of 2 additional opportunities of sputum testing for P. aeruginosa density and sensitivity to ciprofloxacin. Only the sputum sample needs to be retested if other entry criteria are sufficient for the patient to be randomized.
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E.4 | Principal exclusion criteria |
1.Known local or systemic hypersensitivity to fluoroquinolone or quinolone antibiotics,soybeans, or peanuts. 2.Have an exacerbation during the Screening Phase as defined as requiring treatment with inhaled, oral, or intravenous antibiotics prior to the first dose of study drug. 3.Have a diagnosis of cystic fibrosis. 4.Have a diagnosis of allergic brochopulmonary aspergillosis. 5.Have received any intravenous, oral, or inhaled anti-pseudomonal antibiotic within 28 days prior to Visit 1. 6.Have used tizanidine within 28 days prior to Visit 1. 7.Have used supplemental oxygen within 28 days prior to Visit 1. 8.Have used any intravenous or intramuscular corticosteroid or have used oral corticosteroid >10 mg/day or >20 mg every other day within 28 days of Visit 1. 9.Have had changes in either the treatment regimen or initiation of treatment with any of the following medications within 28 days prior to Visit 1: •Azithromycin •Hypertonic saline •Mucolytics •Bronchodilator medications •Oral corticosteroid 10.Have had changes in physiotherapy technique or schedule within 28 days prior to Visit 1. 11.Have a history of solid organ (e.g., lung) transplantation. 12.Have a history of non-tuberculosis mycobacteria requiring treatment within 3 months prior to Visit 1. 13.Have serum creatinine levels ≥ 1.5x upper limit of normal (ULN) at the Screening Visit (Visit 0). 14.Have serum transaminase levels >3x ULN at the Screening Visit (Visit 0). 15.Have a febrile illness within 1 week prior to Visit 1. 16.Have had massive hemoptysis (greater than or equal to 300 mL or requiring blood transfusion) within 6 months prior to Visit 1. 17.Have used any over-the-counter product, herbal product, diet aid, hormone supplement, etc., within 7 days prior to dosing unless approved by both the Principal Investigator and the Sponsor. 18.Have received an investigational drug or device within 28 days prior to Visit 1. 19.Have any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patients’ treatment, assessment, or compliance with the protocol. 20.Have a history or suspicion of unreliability, poor cooperation, or non-compliance with medical treatment. 21.Are unable to use nebulizers. 22.Are unable either to understand the instruction for use of the study drug or to complete the QOL questionnaire at Visit 1. 23.Have previously been enrolled in this study. 24.Are pregnant, plan to become pregnant during this study, are nursing mothers or are unwilling to use an acceptable method of contraception for the duration of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as the mean change in P. aeruginosa density in sputum (log10) CFU/gram of sputum from Baseline to Day 28. The endpoint will be summarized by treatment group and mean change differences will be assessed by statistical methods to be detailed in the statistical analysis plan (SAP). The 2 mL and 3 mL placebo treatment groups will be combined into one arm for both analyses and display purposes.
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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 | No |
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 | 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 | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of treatment visit takes place within two days of Day 28, •Patients who are prematurely withdrawn from study drug should complete the Visit Day 28 assessments. A final visit at Day 56 +/- 2 days will complete the patients participation in the study Patients who discontinue prematurely from the study (either during the On-treatment or Off-treatment Phases) should complete the assessments for Day 56.
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |