E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic Fibrosis with mild to moderate obstructive lung disease and chronic infection with Pseudomonas aeruginosa |
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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 evaluate the safety and tolerability of 500 mg qd of nebulized amikacin in a Sustained Release Lipid Inhalation Targeting (SLIT) formulation following multi-dose (14 days) administration. |
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E.2.2 | Secondary objectives of the trial |
1. To assess changes in Pseudomonas aeruginosa density as a marker of microbiologic efficacy of SLIT Amikacin. Density of P.Aeurignosa in sputum will be calculcated as the log10 value for the sum of all morphtypes (colony-forming units -(CFU) per gram of sputum. 2. To assess the pharmacokinetics of SLIT Amikacin in sputum, plasma and urine |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Written informed consent prior to the performance of any study related procedures 2) Male or female study subjects ≥13 years of age or older and weigth > 40 kilograms 3) Confirmed diagnosis of CF defined as a positive sweat chloride ≥ 60 mEq/liter (by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features of the CF phenotype 4) Chronic infections with P. aeruginosa (defined as = 1 yr of positive cultures) 5) Study subjects must produce a screening sputum (expectorated or induced) that is positive for growth of P. 6) FEV1 = 40% of predicted at Screening 7) SaO2 = 90% at Screening while breathing room air 8) Ability to comply with medication use, study visits, and study procedures as judged by the investigator 9) Ability to produce sputum or be willing to undergo and induction to produce sputum for clinical evaluation (subjects will be asked to be consistent with expectorated or induction for the duration of the study) 10) Clinically stable with no evidance of acute upper or lower respiratory tract infections or current pulmonary |
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E.4 | Principal exclusion criteria |
1) Administration of any investigational drug within 4 weeks of Screening 2) Emergency room visit or hospitalization for CF or respiratory-related illness within 4 weeks prior to screening 3) History of alcohol, medication, or illicit drug abuse within 1 year of Screening 4) History of lung transplantation 5) Female of childbearing potential who is lactating or is not practicing an acceptable method of birth control (e.g.,abstinence, hormonal or barrier methods, partner sterilization, or IUD) 6) Positive pregnancy test. All women of child bearing potential will be tested 7) Use of any anti-pseudomonal antibiotics within 14 days of study treatment 8) Initiation of chronic therapy (ie. TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics) within 60 days of Screening 9) History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of Screening or growth of B. cepacia from the sputum or throat swab culture obtained at Screening 10) History of mycobacterial infection at Screening 11) History of biliary cirrhosis, portal hypertension, or splenomegaly (refer to study manual) or splenomegaly on physical exam at Screening 12) GGTP, AST, or ALT = 2 times the upper limit of normal performed at the local or central laboratories on two occasions at Screening 13) ANC= 1000 performed at the local or central laboratories on two occasions at Screening 14) Serum creatinine > 1.5 times normal performed at the local or central laboratories on two occasions at Screening 15) Changes in their physiotherapy technique or schedule during the week prior to Screening 16) History of daily, continuous oxygen supplementation or requirement for more than 2 L/min at night 17) Change in chest x-ray at Screening (or within the previous 3 months of Screening) with new onset infiltrates or that would compromise the safety of the study patient or the quality of the study data
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Safety measures, including adverse events, vital signs, quality of life assessment, SaO2, FEV1, chemistry and hematology laboratory tests, pulmonary function tests, and sputum culture
Secondary endpoints 2) End-of-treatment (Day 14) change from baseline in density of P. aeruginosa (log10 CFU/g) in sputum. 3) Serum, urine, and sputum amikacin levels will be measured for PK analysis. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | No |
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 | 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 | 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.8.5 | 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 | 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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |