Efficacy, safety and tolerability of Arikace™ compared to TOBI in Cystic Fibrosis patients with chronic infection due to Pseudomonas aeruginosa

Conditions: Pseudomonas aeruginosa pulmonary infection / colonisation in patients with cystic fibrosis
MedDRA version: 14.0Level: PTClassification code 10011763Term: Cystic fibrosis lungSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2011-000441-20-GR

Lead Sponsor: Insmed Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

1) Written informed consent or assent obtained from the patient, parent or legal guardian prior to the performance of any study related procedures
2) Male or female study subjects = 6 years of age (or older, if restricted by the local IRB/EC) at Screening
3) Diagnosis of CF confirmed by a positive sweat test > 60 mEq/liter or > 60 mmol/L or by DNA analysis revealing both mutated alleles consistent with CF disease
4) History of chronic infection with Pa confirmed by three documented positive cultures for Pa within the 2 years prior to Screening with at least one obtained within 6 months prior to Screening. The cultures could be obtained from the following respiratory secretions: sputum, deep throat swabs, or broncho-alveolar lavage fluid specimens
5) Sputum culture positive for Pa at Screening
6) Forced expiratory volume in 1 second (FEV1) = 25% of predicted value at Screening using spirometer provided by sponsor
7) Oxygen saturation (SaO2) = 90% while breathing room air at Screening
8) Ability to comply with study drug use, study visits, and study procedures as judged by the Investigator
9) Ability to expectorate = 0.4 mL of sputum
10) Willingness to have specimens stored for microbiology and pharmacokinetic testing (no genetic testing)
11) Women of childbearing potential must have a negative result on their serum pregnancy test at Screening and use reliable methods of contraception (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) throughout the study duration. Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
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) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Forced Expiratory Volume in 1 second (FEV1) <25% of predicted at Screening using spirometer provided by Insmed
2) History of hypersensitivity to aminoglycosides including tobramycin solution for inhalation
3) Prior exposure to Arikace™ (including clinical study)
4) History of major complications of lung disease (including atelectasis, pneumothorax, major pleural effusion), within 8 weeks prior to Screening
5) Hemoptysis of =60 mL in a 24-hour period within 4 weeks prior to Screening
6) History of acute pulmonary exacerbation requiring antibiotic treatment within 4 weeks prior to Screening
7) History of upper respiratory tract infection within 2 weeks prior to Screening
8) Use of antipseudomonal antibiotics (IV antibiotics, inhalation antibiotics, or oral) within 4 weeks prior to Day 1
9) Radiologic finding of new pulmonary infiltrate(s) within 3 months prior to Screening, or presence of other abnormalities suggesting clinically significant active pulmonary disease other than CF
10) Initiation of chronic therapy (e.g., TOBI®, Colomycin®, other inhaled antibiotics, high-dose ibuprofen, bronchodilators, inhaled anti-inflammatory agents including steroids, low dose maintenance steroids, rhDNase, hypertonic saline, macrolides) within 4 weeks prior to study Day 1
11) History of positive culture for Burkholderia cepacia within 2 years prior to Screening
12) History of pulmonary tuberculosis or non-tuberculous mycobacterial lung disease treated within 2 years prior to Screening or requiring treatment at the time of screening
13) History of Allergic Broncho-Pulmonary Aspergillosis requiring systemic steroid treatment or any other condition requiring systemic steroids at a dose = equivalent of 10 mg/day of prednisone within 3 months prior to Screening
14) Presence of any clinically significant cardiac disease as determined by investigator and/or, if QTc data are available, QTc prolongation > 450 msec (0.450 seconds) for males or QTc > 470 msec (0.470 seconds) for females or QTc prolongation > 440 msec (0.440 seconds) for all subjects 6 to 12 years of age
15) Acquired and primary immunodeficiency syndromes
16) History of hepatitis C or chronic active hepatitis B infection
17) Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within one year prior to Screening or anticipated during the study period
18) History of biliary cirrhosis with portal hypertension
19) History of lung transplantation
20) Elevated AST, ALT or GGT = 3× the upper limit of normal (ULN) at Screening
21) Absolute neutrophils count = 1000 at Screening
22) Serum creatinine > 2× ULN at Screening
23) Daily, continuous oxygen supplementation
24) Supplemental oxygen requirement of greater than 2 L/min at night
25) Administration of any investigational products within 8 weeks prior to study Day 1
26) Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
27) History of alcohol, medication, or illicit drug abuse within the 1 year prior to Screening
28) Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study
29) Positive pregnancy test or lactation at Screening. All women of child bearing potential will be tested for pregnancy. Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year),

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objectives of the study are to evaluate the efficacy, safety and tolerability of 3 cycles (28 days on-treatment and 28 days off treatment) of Arikace™ therapy. Change in pulmonary function, time to first pulmonary exacerbation, need for antipseudomonal antibiotics, change in sputum quantitative microbiology, hospitalization, patient reported symptoms/outcomes, and time off work/school will be assessed. Safety and tolerability will be evaluated throughout the study.;Secondary Objective: ;Primary end point(s): The relative change in Forced Expiratory Volume in 1 second (FEV1 (liters)) from baseline (Day 1) to the end of the study (Day 168);Timepoint(s) of evaluation of this end point: Days 1, 168

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Relative change in FEV1 (liters) from Day 1 to the end of study<br>2) Relative change in FEV1 (% predicted) from Day 1 to the end of study<br>3) Time to first protocol defined pulmonary exacerbation and proportion of subjects experiencing a protocol defined pulmonary exacerbation<br>4) Time to first antipseudomonal antibiotic treatment for protocol defined pulmonary exacerbation<br>5) Change in log CFU Pa from baseline throughout study<br>6) Time to and number of hospitalizations for any cause<br>7) Change in respiratory symptoms from baseline throughout study as measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R);Timepoint(s) of evaluation of this end point: 1) Day 1, 14, 28, 57, 84, 113 and 140<br>2) Day 1, 14, 28, 57, 84, 113, 140 and 168<br>5) Day 1, 14, 28, 57, 84, 113, 140, 168<br>7) Day 1, 14, 28, 57, 84, 113, 140 and 168

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