E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011763 |
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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 |
To investigate the safety and tolerability of heparin inhalation powder in patients with CF. |
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E.2.2 | Secondary objectives of the trial |
To investigate the pharmacodynamics To evaluate efficacy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female ≥16 years; 2. Non-smoker; 3. Written informed consent obtained prior to any trial specific procedures; 4. Confirmed diagnosis of CF lung disease (i.e., respiratory clinical symptoms and positive sweat test or disease inducing mutations) by CF expert / Investigator; 5. Patient considered, in the Investigator s opinion, to be clinically stable and has at Screening and Baseline an FEV1 40 - 90% of predicted value for age, sex and height; 6. FEV1 value at Baseline is within +/-15% of FEV1 value 4 weeks earlier at Screening; 7. Regular mucus production due to CF; 8. Ease of sputum expectoration (i.e., clearability) VAS score of  80 mm; 9. Neutrophil elastase and / or IL-8 levels above detectable levels and/or upper limit of normal range for specified laboratory; 10. Adequate contraceptive measures (the subject [and his/her partner] should use adequate contraceptive measures, consisting of two forms of contraception, at least one of which must be a barrier method); 11. Able to comply with all the requirements of the protocol; 12. Able to use inhaler satisfactorily. |
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E.4 | Principal exclusion criteria |
1. Known sensitivity to any preparation of inhaled or parenteral heparin or the excipient leucine; 2. Any contra indication to Monoparin considered clinically relevant; 3. Increased bleeding risk 4. Clinically significant liver 5. Clinically significant serious disease or organ system disease not currently controlled / stable on present therapy; 6. Patients with a history of clinically or radiologically diagnosed aspergilloma; 7. Pregnancy at Screening; or lactation; 8. Planned hospitalisations which could interfere with trial compliance; 9. Previous thoracic or scheduled major surgery during trial period; 10. Previous or current regular use of proscribed medication defined as: a. Chronic / regular non-steroidal anti-inflammatory drug (NSAID) use (i.e., more than 3 times per week); b. Any regular anti coagulant therapy in the 2 weeks prior to Screening; c. Any previous use of inhaled heparin; d. Use of parenteral heparin 1 month prior to Screening; e. Use of other investigational drugs 1 month prior to Screening; f. Chronic / regular corticosteroid (1 month prior to Screening) g. Any regular inhaled tobramycin (Tobi) or other antibiotic use for oral, inhaled or parenteral treatment to be stable for at least 1 month prior to Screening and during the course of the trial h. Modification of medication to treat respiratory disease between Screening and Baseline (Day 1) i. Patients prescribed mucolytics, or hypertonic saline, but who have been taking them for less than 3 months prior to Screening are excluded. 11. Unable for any other reason to satisfactorily comply with the protocol (e.g., attendance for trial visits, treatment or assessments). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of Pharmacodynamic Endpoints The PD variables are: Expectorated mucus measurement parameters Induced sputum markers EBC pH levels Plasma markers Coagulation parameters. Evaluation of Efficacy Endpoints The efficacy variables are: VAS parameters Volume and weight of 24 hour cumulative expectorated sample Microbiology assays of expectorated sputum Pulmonary function parameters FEV1, FVC and FEF25-75, and SaO2 by finger oximetry at rest, post physiotherapy and before induced sputum; Response to the CFQ: responses to the questionnaire are to be measured by a six point Likert scale |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | 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.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 | 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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Tratti dell`ultima visita dell`ultimo soggetto inserito nella sperimentazione |
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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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |