Efficacy, safety and tolerability of Arikace™ compared to placebo in Cystic Fibrosis patients with chronic infection due to Pseudomonas Aeruginosa
- Conditions
- Pseudomonas aeruginosa pulmonary infection / colonisation in patientswith cystic fibrosisMedDRA version: 14.0Level: PTClassification code 10011763Term: Cystic fibrosis lungSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2011-000442-38-PL
- Lead Sponsor
- Insmed Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
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/L 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) History of documented pulmonary exacerbation requiring treatment with antibiotics in the 12 months prior to Screening
6) Sputum culture positive for Pa at Screening
7) Forced expiratory volume in 1 second (FEV1) = 25% of predicted value at Screening using spirometer provided by sponsor
8) Oxygen saturation (SaO2) = 90% while breathing room air at Screening
9) Ability to comply with study drug use, study visits, and study procedures as judged by the Investigator
10) Ability to expectorate = 0.4 mL of sputum
11) Willingness to have specimens stored for microbiology and pharmacokinetic testing (no genetic testing)
12) 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
1) Forced expiratory volume in 1 second (FEV1) <25% of predicted value at Screening using spirometer provided by Insmed
2) History of hypersensitivity to aminoglycosides
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 pulmonary tuberculosis or non-tuberculous mycobacterial lung disease treated within 2 years prior to Screening or requiring treatment at the time of Screening
12) 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
13) 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 > 470 msec (0.470 seconds) for females or >440 msec (0.440 seconds) for all subjects 6 to 12 years of age
14) Acquired and primary immunodeficiency syndromes
15) History of hepatitis C or chronic active hepatitis B infection
16) 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
17) History of biliary cirrhosis with portal hypertension
18) History of lung transplantation
19) Elevated AST, ALT or GGT = 3× the upper limit of normal (ULN) at Screening
20) Absolute neutrophils count = 1000 at Screening
21) Serum creatinine > 2× ULN at Screening
22) Daily, continuous oxygen supplementation
23) Supplemental oxygen requirement of greater than 2 L/min at night
24) Administration of any investigational products within 8 weeks prior to study Day 1
25) Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
26) History of alcohol, medication, or illicit drug abuse within the 1 year prior to Screening
27) Smoking tobacco or any substance within 6 months prior to Screening or anticipated inability to refrain from smoking throughout the study
28) 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), or surgically or naturally sterile
29) Any condition which in the opinion of the investigator interferes with ability to safely complete the study or ad
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy, safety and tolerability of Arikace™ treatment for 28 days, with a 56 day follow-up period, in CF subjects. Time to pulmonary exacerbation, change in pulmonary function, change in sputum quantitative microbiology, hospitalization, need for anti-pseudomonal antibiotics, patient reported symptoms/outcomes and time off work/school will be assessed. Amikacin pharmacokinetics will be assessed in a subset of subjects. Safety and tolerability will be evaluated throughout the 28 day treatment period and the 56 day follow-up period.;Secondary Objective: ;Primary end point(s): Time to first protocol defined pulmonary exacerbation;Timepoint(s) of evaluation of this end point: Day 1 to Day 84
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1) Relative change in Forced Expiratory Volume in 1 second (FEV1)<br>(liters) and FEV1 (% predicted)<br>2) Proportion of subjects experiencing protocol defined exacerbations<br>3) Time to first antipseudomonal antibiotic treatment for protocol<br>defined pulmonary exacerbation<br>4) Time to first hospitalization for any cause and number of<br>hospitalizations<br>5) Change in log CFU Pa <br>6) Change in log CFU Burkholderia sp;Timepoint(s) of evaluation of this end point: 1) Day 1 to Days 28, 56 and 84<br>5) Day 1, Day 28<br>6) Day 1, Day 28