E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis |
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E.1.1.1 | Medical condition in easily understood language |
Chronic lung infections caused by specific bacteria called Pseudomonas aeruginosa in patients with cystic fibrosis. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011763 |
E.1.2 | Term | Cystic fibrosis lung |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 |
Tolerability and Safety of Open Label inhaled colistimethate sodium, comparing once daily (QD) with twice daily (BID) Administration for 28 days, measured by safety and respiratory tolerability events. |
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E.2.2 | Secondary objectives of the trial |
Additional assessments of pulmonary function and clinical events as measured by • Pulmonary function (ppFEV1) • Pulmonary exacerbations (PEx), severity of PEx, hospitalizations • Additional antibacterials taken |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects, ages 12 years and older: a. Step A: ages 18 years and older b. Step B: ages 12 years and older 2. Previous diagnosis of cystic fibrosis as confirmed by: a. documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test prior to initiation of therapy with CFTR modulators (e.g., elexacaftor, tezacaftor, ivacaftor), if applicable; or b. two well-characterized genetic mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene; and c. symptoms characteristic of cystic fibrosis 3. Persistent airways infection with P. aeruginosa as evidenced by: a. positive P. aeruginosa in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to screening; or b. history of inhaled antibiotic treatment for suppression of P. aeruginosa 4. Stable treatment regimen of CF therapeutics for at least 2 months prior to randomization defined as: a. regimen of inhaled antibacterials for either at least 2 months of continuous therapy or at least a total of 56 days of consecutive on treatment periods in case of cyclical therapy (e.g. 28 day on treatment, followed by 28 days off treatment, followed by another 28 days on treatment) prior to randomization AND b. no changes in either any current treatment regimen or initiation of treatment with hypertonic saline, dornase alfa, CFTR modulators or other CF specific therapeutics. 5. FEV1 at screening of ≥30% of predicted values 6. Arterial oxygen saturation (SpO2) ≥ 90% on room air at screening |
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E.4 | Principal exclusion criteria |
1. Current need for daily continuous O2 or requirement for > 2 liters/min at night 2. History of any investigational drug/device use within 28 days of screening or within 6 half-lives of investigational drug (whichever is longer) 3. History of lung or liver transplantation 4. History or current diagnosis of myasthenia gravis or porphyria 5. Abnormal renal or hepatic function measured in serum chemistry at screening (AST or ALT > 3x upper limit of normal (ULN); Creatinine > 2x ULN) 6. Positive pregnancy test at screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of observed safety events during the 28-day treatment period in each treatment arm |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Number of observed safety events during the 42-day follow-up period in each treatment arm 2. Number of observed safety events during the 169 days total follow-up period in each treatment arm 3. Absolute change from baseline (Day 1) to Day 14 and Day 28 in ppFEV1 in each treatment arm 4. Change in mean absolute ppFEV1 from baseline (after SABA) to post dose values during serial spirometry at Day 1 and Day 28 in each treatment arm 5. Number of newly diagnosed total and severe PEx from baseline (Day 1) to Day 28, to Day 42 and to 169 in each treatment arm 6. Additional antibacterials taken 7. Number of hospitalizations from baseline (Day 1) to Day 28, to Day 42 and to Day 169 in each treatment arm |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 42 days 2. 169 days 3. Day 14 and Day 28 4. Day 1 and Day 28 5. Day 28, Day 42 and Day 169 6. Day 28 7. Day 28, Day 42 and Day 169 |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
different dose of the same medicinal product |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Ukraine |
Serbia |
Greece |
Hungary |
Poland |
Slovakia |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |