E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic Fibrosis with Pseudomonas aeruginosa infections |
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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 |
E.1.2 | Term | Cystic fibrosis lung |
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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 |
The primary objective of the study is to determine the bioavailability in the Tobramycin 100 PARI/eFlow treatment group compared to the TOBI/PARI LC PLUS compressor treatment group. Both groups of patients will be treated during a period 28 days, receiving the study medication twice a day.
1. Evaluation of plasma and sputum levels of the new formulation Tobramycin 100 PARI containing 150 mg / 1.5 ml Tobramycin nebulized via eFlow®, compared with the registered TOBI® nebulized via PARI LC PLUS.
2. Evaluation of safety data: safety of Tobramycin 100 PARI will be determined for 28 days treatment in 30 CF patients. The active control arm has 30 CF patients receiving TOBI standard therapy.
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E.2.2 | Secondary objectives of the trial |
bioavailability: - sputum Tobramycin levels on days 1, 7 and 28 - plasma trough Tobramycin levels on days 1 and 28
tolerability: bronchospasm: number of patients with bronchospasm (defined as a fall in FEV1 > 15% at 30 min after end of inhalation) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed Informed Consent before the screening visit examinations. - Patients older 8 years of age. - Subjects with CF: Documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) or homozygosity for AF508 genetic mutation (or heterozygosity for two well characterized mutations) and two clinical findings consistent with CF. - Sexually active females of childbearing potential will be included only if they already use for other reasons a highly effective contraceptive method prior study initiation. - Ability to perform reproducible spirometry. - FEV1 lower then 40 % of predicted, based on gender, age and height. - No change in FEV1 more than 20% within one month period prior to screening visit. - Stable condition with no exacerbation requiring IV antibiotics or hospitalization within one month period prior to screening visit. - Documented P. aeruginosa presence in a sputum/throat culture within 6 months prior to screening or at least two consecutive positive P. aeruginosa cultures within one year. - Resting oxygen saturation with pulse oximetry at least 88% on room air. |
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E.4 | Principal exclusion criteria |
- Use of investigational medications within 30 days before study entry or during the trial. - Active drug and alcohol abuse. - Inability to handle the study inhalers or to inhale the test formulations. - Inability to adhere to the requirements of the protocol. - FEV1 < 40% predicted. - Administration of any anti-pseudomonas antibiotics (with the exception of macrolide) by any route within 7 days prior to initial study drug administration. - Positive urine pregnancy test. Test must be performed at screening. - Severe respiratory infection within one month prior to screening, which requires hospital admission or treatment with intravenous antibiotics. - Active, severe Hemoptysis, defined as Hemoptysis > 60 cc at any time within thirty days prior to study drug administration. - Known local or systemic hypersensitivity to aminoglycosides. - Elevated serum creatinine > 1, 2 mg/dl or BUN equal 20 mg/dl, or an abnormal urine analysis defined as having more than + proteinuria in urinstix. - History of sputum culture or throat swab culture yielding B. cepacia in the previous 12 months and/or sputum or throat swab culture yielding B. cepacia at screening. - Presence of allergic bronchopulmonary aspergillosis (ABPA). - Significant liver disease (> 2x Upper Standard limits and no thrombocytopenia or clinical liver disease). - Patients with history of GI bleeding. - Patients with auditory or/and vestibular dysfunctions. - Patients with neuromuscular diseases. - Women of childbearing potential and sexually active who are not already using a high effective method of contraception. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetics: plasma Tobramycin levels on day 7: trough and peak levels and AUC (Area under the curve) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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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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 | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 2 |