Cystic fibrosis MedDRA version: 9.1 Level: LLT Classification code 10011762 Term: Cystic fibrosis
Conditions
Interventions
Product Name: Liposomal Amikacin (Arikace™)
Pharmaceutical Form: Nebuliser suspension
Sponsors
Transave, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 or older. To be eligible, study subjects must also have history of sputum containing Pseudomonas aeruginosa. 1) Written informed consent 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 randomization Main criteria for inclusion of patients participating in the 6 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 Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 infection 11)History of biliary cirrhosis, 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 6 months extension period: 1) Patient meets all 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To evaluate the safety and tolerability of 28 days of daily dosing of two dose cohorts of nebulized Arikace™, liposomal amikacin for inhalation;Secondary Objective: 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;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 | — |
Countries
Belgium, Hungary
Outcome results
None listed