E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10011762 |
E.1.2 | Term | Cystic fibrosis |
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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 |
1.To evaluate the safety and tolerability of 28 days of daily dosing of two dose cohorts of nebulized Arikace™, liposomal amikacin for inhalation |
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E.2.2 | Secondary objectives of the trial |
1. To assess pharmacokinetics (PK) of Arikace™ in serum and urine, and evaluate sputum amikacin levels 2. To evaluate change in Pulmonary function 3. To evaluate change in density of Pseudomonas aeruginosa in sputum. 4. To evaluate time to and duration of systemic antipseudomonal rescue therapy. 5. To evaluate change in Quality of Life (CFQ-R) measurements 6. To evaluate the longer term safety, tolerability and efficacy of 560 mg once daily dose of Arikace™ administered for six cycles over eighteen months. Each cycle comprising of 28 days of treatment followed by 56 days off treatment. 7. Exploratory evaluation of durability of clinical benefit
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
CF study subjects with mild to moderate obstructive lung disease (FEV1% predicted ≥ 40%) will be eligible for enrollment. Study subjects must be ≥ 6 years old. To be eligible, study subjects must also have history of sputum containing Pseudomonas aeruginosa.
1) Written informed consent obtained from the patient or designated legal guardian prior to the performance of any study related procedures 2) Male or female study subjects ≥ 6 years of age or older 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) History of chronic infection with P. aeruginosa (defined as 3 documented positive cultures in the prior 2 years of which at least one was obtained in the 3 months prior to randomization. The cultures could be obtained from the following respiratory secretions: sputum, throat swabs, nasopharyngeal swabs or broncho-alveolar lavage fluid specimens) 5) Study subjects must produce a screening specimen (expectorated or induced sputum, throat swabs, nasopharyngeal swabs or broncho-alveolar lavage fluid) that is positive for growth of P. aeruginosa 6) FEV1 ≥ 40% of predicted at Screening 7) SaO2 ≥ 90% at Screening while breathing room air 8) Ability to comply with study medication use, study visits, and study procedures as judged by the investigator 9) Ability to produce 0.5 grams sputum or be willing to undergo an induction to produce sputum for clinical evaluation 10)Clinically stable with no evidence of acute upper or lower respiratory tract infection or history of pulmonary exacerbation within the 4 weeks prior to screening
Main criteria for inclusion of patients participating in the 18 months extension period: 1) Written informed consent obtained from the patient or designated legal guardian prior to the performance of any study related procedures in the extension period 2) Patient meets all of the above listed inclusion criteria (1-10) of the main protocol
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E.4 | Principal exclusion criteria |
1) Administration of any investigational drug within 8 weeks prior to Screening 2) Emergency room visit or hospitalization for CF or respiratory-related illness within the 4 weeks prior to screening 3) History of alcohol, medication, or illicit drug abuse within the 1 year prior to 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 (IV antibiotics, all inhalation antibiotics, oral fluoroquinolones) within the 28 days prior to screening. 8) Initiation of chronic therapy (i.e. TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics) within the 28 days prior to screening 9) History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of Screening 10)History of mycobacterial or Aspergillus infection 11)History of biliary cirrhosis with portal hypertension, or splenomegaly (refer to study manual) 12)GGT, AST, or ALT ≥ 3 times the upper limit of normal at Screening visit 13)ANC ≤ 1000 performed at Screening visit 14)Serum creatinine > 1.5 times normal performed at Screening visit 15)History of daily, continuous oxygen supplementation or requirement for more than 2 L/min at night 16)Change in chest x-ray at screening (or within the 3 months prior to screening) with new onset infiltrates or that which compromise the safety of the study patient or the quality of the study data
Main criteria for exclusion of patients participating in the 18 months extension period: 1) Patient meets any criteria for exclusion as listed above in the main protocol 2) Patient which met any criteria for study drug discontinuation in the main protocol (see section 5.3 Criteria for Study Drug Discontinuation)
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoints: • To evaluate the safety and tolerability of 28 days of daily dosing of two dose cohorts of nebulized Arikace™, liposomal amikacin for inhalation. Secondary Endpoints: • To assess pharmacokinetics (PK) of Arikace™ in serum and urine, and evaluate sputum amikacin levels • To evaluate change in Pulmonary function • To evaluate change in density of Pseudomonas aeruginosa in sputum. • To evaluate time to and duration of systemic antipseudomonal rescue therapy. • To evaluate change in CFQ-R measurements. • To evaluate the safety, tolerability and efficacy of Arikace™ when administered in an “on-off” treatment regimen for an additional six cycles over a 18 months period • Exploratory evaluation of durability of clinical benefit over a 18 months period
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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 | 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 | No |
E.8.1.1 | Randomised | No |
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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |