E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Repeated or extended dosing of aminoglycosides may cause damage to the proximal tubuli, resulting in renal impairment. Renal impairment affects up to 40 % of adult CF patients, measured after estimation using an appropriate formula. The true number is probably even greater. |
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MedDRA Classification |
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 compare renal elimination constant in CF patients receiving a daily intravenous dose of tobramycin in the morning compared to patients receiving a daily intravenous dose of tobramycin in the evening. |
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E.2.2 | Secondary objectives of the trial |
To compare biochemical signs of nephrotoxicity in patients who receive their dose of aminoglycoside in the morning against patients who receive their dose of aminoglycoside in the evening. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria : - Age: ≥ 18 years - a diagnosis of cystic fibrosis (ie, sweat chloride _60 mmol/L or a genotype associated with cystic fibrosis) - chronic infection with Pseudomonas aeruginosa with the most recently isolated organism showing sensitivity to tobramycin. - Pulmonary exacerbation as defined by Fuchs and colleagues
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E.4 | Principal exclusion criteria |
- use of nephrotoxic drugs (NSAID´s, furosemide, vancomycin) - allergy for aminoglycosides - granulocytopenia (<1,0 x 109/L) - pregnancy - calculated GFR < 40 ml/min - pre-existing hearing impairment (_20 dB hearing level at any two frequencies between 2kHz and 8 kHz on the standard audiogram)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point will be a significant or non-significant difference in the rate elimination constant (Kelm) between CF patients receiving a daily intravenous dose of tobramycin in the morning and CF patients receiving a daily intravenous dose of tobramycin in the evening. |
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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 | No |
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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
dosing tobramycin in the morning vs. evening |
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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 |
controlled by comparing morning arm to evening arm |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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 trial will end when the required data of at least 28 patients, who have completed 2 weeks of standard tobramycin therapy is available. |
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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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |