E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic fibrosis |
Cystic fibrosis |
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E.1.1.1 | Medical condition in easily understood language |
Cystic fibrosis |
Taaislijmziekte |
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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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate whether pharmacokinetics of the recommended dose of inhaled tobramycin, defined as serum tobramycin Area Under the Curve (AUC0-24hr), with the I-neb (75 mg) is equivalent to the PariLCPlus (300 mg) nebuliser in children with CF aged 6-18 years. |
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E.2.2 | Secondary objectives of the trial |
1) To assess safety of I-neb tobramycin inhalation therapy, 2) to compare pharmacokinetics of I-neb tobramycin inhalation in children with CF aged 6-11 years with children aged 12-18 years and 3) to compare patient compliance and satisfaction with both nebulisers. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The criteria of inclusion will be the following:
• Clinical diagnosis of CF and a positive sweat test or two CF-related mutations;
• Either: early PA infection or colonization with PA requiring eradication with inhaled tobramycin, or: chronic PA colonization requiring maintenance therapy with inhaled tobramycin;
• Age 6-18 years;
• Ability to breathe through a mouthpiece and to use both types of inhalers;
• Ability to perform lung function tests;
• Written informed consent (parents; >12 years: child and parents).
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E.4 | Principal exclusion criteria |
The criteria of exclusion will be the following:
• Acute exacerbation of pulmonary infection;
• Known impaired kidney function (estimated creatinine clearance < 60 ml/min);
• Start of nephrotoxic or ototoxic drugs, e.g. aminoglycosides, within 1 month prior to start or during the study;
• Therapy (e.g. furosemide) or disease which may complicate evaluation of the study protocol, as judged by the investigator;
• Participation in another drug-investigating clinical study at the start or within 1 month prior to the start;
• Inability to follow instructions of the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: systemic bioavailability of inhaled tobramycin, defined as serum tobramycin AUC0-24hr. |
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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) |
Secondary endpoints will include:
• Change in hearing function (measured by HFPTA and DPOAE);
• Change in NAG/creatinine ratio as measure of early renal toxicity;
• Serum tobramycin peak and trough levels;
• Change in FEV1 before and after nebulisation (safety parameter);
• Compliance rate;
• Patient satisfaction (use/cleaning of device);
• Differences in AUC0-24 between age groups 6-11 and 12-18 years.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Tobramycin nebulisation with PariLCPlus nebuliser (standard) compared to I-neb nebuliser (new) |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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Untill 24 patients are included |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |