E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic fibrosis in children aged 6 to 17 years |
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E.1.1.1 | Medical condition in easily understood language |
Cystic fibrosis in children aged 6 to 17 years |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
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 |
To determine the effect of eight weeks of twice-daily treatment with inhaled dry powder mannitol on lung function (FEV1) in subjects with CF who are aged six to seventeen years |
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E.2.2 | Secondary objectives of the trial |
• To determine the effect of inhaled mannitol on FVC; • To determine the effect of inhaled mannitol on FEF25-75 (exploratory objective) and • To assess the safety of inhaled mannitol. • To evaluate the difference in treatment induced sputum weight in patients treated with inhaled mannitol compared to those treated with placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Personally provide, or have a legal guardian provide written informed consent to participate in the trial, according to local regulations; 2. rhDNase and maintenance antibiotic use is allowed but treatment must have been established at least 3months prior to screening. The subject must remain on rhDNase and / or maintenance antibiotics for the duration of the trial. The subject must not commence treatment with rhDNase or maintenance antibiotics during the trial; 3. Have a confirmed diagnosis of cystic fibrosis (sweat test result >= 60 mEq/L chloride and/or genotyping showing two identifiable mutations consistent with a diagnosis of cystic fibrosis); 4. Be aged >= 6 years and < 18 years; 5. Have a percentage of predicted FEV1 of >= 30% and < 90% at Screening (Visit 0). Percentage of predicted FEV1 will be calculated using Wang for children aged < 8 years, and using NHanes III for those >= 8 years; and 6. Be able to perform all the techniques necessary to measure lung function.
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E.4 | Principal exclusion criteria |
1. Be using maintenance nebulised hypertonic saline Be considered “terminally ill”; eligible for lung transplantation, or have received a lung transplant previously; 2. Require home oxygen or assisted ventilation; 3. Have had an episode of massive haemoptysis defined as acute bleeding ≥240 ml in a 24-hour period and/or recurrent bleeding ≥100 ml/day over several days in the three-months prior to Screening (Visit 0);
4. Have a known intolerance to mannitol; 5. Be taking non-selective beta blockers; 6. In the three months prior to Screening (Visit 0) have had a myocardial infarction; a cerebral vascular accident; major ocular, abdominal, chest or brain surgery; 7. Have a known cerebral, aortic or abdominal aneurysm; 8. Be currently participating in, or have participated in another investigative drug trial within four weeks of Screening (Visit 0); 9. Be pregnant or breastfeeding, or plan to become pregnant whilst in the trial; 10. For females of childbearing potential (at the discretion of the investigator), be using an unreliable form of contraception; 11. Have a “failed” or “incomplete” mannitol tolerance test; or 12. Have any concomitant medical, psychiatric, or social condition that, in the Investigator’s opinion, would put the subject at significant risk, may confound the results or may significantly interfere with the subject’s participation in the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The absolute change from each baseline to week 8 of each treatment period in percentage of predicted FEV1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoint will be evaluated at the end of the trial. |
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E.5.2 | Secondary end point(s) |
• Change in percentage of predicted FVC between placebo and mannitol treatment • Change in percentage of predicted FEF25-75 between placebo and mannitol treatment (exploratory endpoint) • Adverse events, vital signs and physical examination • Treatment induced sputum weight
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints will be evaluated at the end of the trial. |
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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 | 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) | 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 | No |
E.8.1.6 | Cross over | Yes |
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 | 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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
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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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Trial is ended approximately one week after LVLS, after the last subject receives telephone contact to follow up on any adverse events following the last dose of study drug. |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |