Study of Aztreonam for Inhalation in Children with Cystic Fibrosis and New Infection of the Airways by Pseudomonas aeruginosa bacteria

• Register: EUCTR
• Last refreshed on: 10 June 2014
• Main ID: EUCTR2011-001255-36-IE
• Date of registration: 24/10/2011
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: Study of Aztreonam for Inhalation in Children with Cystic Fibrosis and New Infection of the Airways by Pseudomonas aeruginosa bacteria
• Scientific title: Open-Label Phase 2 Trial to Evaluate the Safety and Efficacy of Aztreonam 75 mg Powder and Solvent for Nebuliser Solution/Aztreonam for Inhalation Solution (AZLI) in Pediatric Patients with Cystic Fibrosis (CF) and New Onset Lower Respiratory Tract Culture Positive for Pseudomonas aeruginosa (PA) - ALPINE (Aztreonam Lysine for Pseudomonas Infection Eradication)
• Date of first enrolment: 06/02/2012
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001255-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Belgium, France, Germany, Ireland, Italy, Netherlands, Poland, Spain, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Gilead Sciences International Limited

• Name: Clinical Trials Information
• Affiliation: Gilead Sciences International Limited

Key inclusion & exclusion criteria

Inclusion criteria:
• Males or females aged 3 months to less than 18 years.
• Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:Documented sweat chloride = 60 mEq/L by quantitative pilocarpine iontophoresis
test OR Abnormal nasal transepithelial potential difference test OR Two well-characterized, disease-causing genetic mutations in the CF transmembrane
conductance regulator (CFTR) gene AND One or more clinical features consistent with CF.
• Documented new onset of positive lower respiratory tract culture for PA within 30 days of study entry (screening visit) defined as either first lifetime documented PA-positive culture, or PA recovered after at least a 2-year history of PA-negative respiratory cultures (at least 2 cultures per year)
• FEV1 = 80% predicted (for patients = 6 years of age).
• Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would require administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.
• All sexually active female subjects who are of childbearing potential must agree to use a
highly effective method of contraception during heterosexual intercourse throughout the
study. Females utilizing hormonal contraceptives as a birth control method must have
used the same method for at least 3 months prior to study drug dosing.
• Male subjects must agree to use barrier contraception (condom with spermicide) during
heterosexual intercourse from screening through to study completion and for 90 days
from the last dose of study investigational medicinal product.
• Subjects and/or parent/guardian must be able to give written informed consent prior to
any study related procedure.
Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) no
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:
• Use of IV or inhaled antipseudomonal antibiotics within 2 years of study entry
(screening visit)
• Use of oral antipseudomonal antibiotics within 30 days of study entry (screening visit)
• History of sputum or throat swab culture yielding Burkholderia spp. within 2 years prior
to screening visit
• History of local or systemic hypersensitivity to monobactam antibiotics
• History of intolerance to inhaled short acting ß2 agonists
• History of lung transplantation
• History of AZLI (or Cayston®) administration
• Administration of any investigational drug or device within 28 days prior to Screening
Visit or within 6 half-lives of the investigational drug (whichever is longer)
• Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone
per day or 20 mg prednisone every other day
• Current requirement for daily continuous oxygen supplementation or requirement of
more than 2 L/minute at night
• Hospitalization for pulmonary-related illness within 28 days prior to Screening Visit
• Changes in or initiation of chronic azithromycin treatment within 28 days prior to
Screening Visit
• Changes in antimicrobial, bronchodilator (BD), corticosteroid, dornase alfa, or hypertonic
saline medications within 7 days prior to Screening Visit; for subjects on a stable regimen
of hypertonic saline (28 days on/28 days off), beginning or ending a cycle of hypertonic
saline is allowed
• Changes in physiotherapy technique or schedule within 7 days prior to Screening Visit
• Abnormal renal or hepatic function results at most recent test within the previous 12
months, defined as:
— AST or ALT > 5 times upper limit of normal (ULN), or
— Serum creatinine > 2 times ULN for age
• Pregnant or lactating females; a negative urine pregnancy test is required for all female
subjects of childbearing potential (unless surgically sterile), and confirmatory serum
pregnancy test in the event of an initial positive urine test result
• Any serious or active medical or psychiatric illness (including drug or alcohol abuse),
which in the opinion of the investigator, would interfere with subject treatment,
assessment, or compliance with the protocol
• Presence of a condition or abnormality that would compromise the patient’s safety or the
quality of study data, in the opinion of the investigator


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic fibrosis and new onset lower respiratory tract culture positive for Pseudomonas aeruginosa
MedDRA version: 14.1 Level: LLT Classification code 10068288 Term: Cystic fibrosis pulmonary exacerbation System Organ Class: 10021881 - Infections and infestations
MedDRA version: 14.1 Level: PT Classification code 10070608 Term: Infective pulmonary exacerbation of cystic fibrosis System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Cayston
Aztreonam 75 mg powder and solvent for nebuliser solution
Product Name: Aztreonam for Inhalation Solution
Product Code: AZLI
Pharmaceutical Form: Powder and solvent for nebuliser solution
INN or Proposed INN: AZTREONAM
CAS Number: 78110-38-0
Current Sponsor code: AZLI
Other descriptive name: N/A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-

Primary Outcome(s)

Main Objective: To evaluate safety and efficacy of a 28-day course of AZLI in patients with initial PA pulmonary colonization/infection at Day 28 (end of treatment) and Days 56, 112, and 196 (1, 3, and 6 months after the end of treatment, respectively).

Primary end point(s): The primary objective of this study is to evaluate the proportion of patients with PA-negative cultures at all time points during a 6-month monitoring period (through Day 196) after cessation of active treatment; microbiological cultures will be obtained at Baseline, Day 28 (end of treatment), Day 56 (1 month after
completing AZLI), Day 112 (3 months after completing AZLI), and Day 196 (6 months after completing AZLI). PA-specific antibody titers will be obtained at Baseline, Day 28, and Day 196. Safety endpoints will include adverse events, airway reactivity (study drug-induced bronchspasm), vital signs, blood biochemistry
and hematology.

Secondary Objective: Below the age of 6 years pharmacokinetic data will be assessed.

Timepoint(s) of evaluation of this end point: Microbiological cultures will be obtained at Baseline (Day 1), Day 28 (end of treatment), Day 56 (1 month after completing AZLI), Day 112 (3 months after completing AZLI), and Day 196 (6 months after completing AZLI). PA-specific antibody titers will be obtained at Baseline, Day 28, and Day 196. Airway reactivity (study drug-induced bronchospasm) will be assessed at Baseline and Day 28. Blood biochemistry and hematology will be assessed at Screening, Baseline, Day 28 and Day 196. Adverse events and vital signs will be assessed at Screening, Baseline, Day 28, Day 56, Day 112 and Day 196.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: In patients = 6 years of age at Days 28, 56, 112, and 196:
• Change from baseline in FEV1 % predicted;
• Change from baseline in CFQ-R Respiratory Symptoms Score (RSS).
In all patients at Days 28, 56, 112 and 196:
• Proportion of patients with PA-negative cultures;
• Change from baseline in weight, height, and body mass index (BMI).
In all patients at Screening and Days 1, 28, 56, 112 and 196:
• Use of additional (non-study) antipseudomonal antibiotics (as a marker for PA exacerbation).
In patients < 6 years of age:
• Pharmacokinetics: 1 peak plasma sample will be obtained 1 hour after the first dose of AZLI (Day 1); 1 trough plasma sample will be obtained immediately prior to the last dose of AZLI (Day 28 + 4 days).

Secondary end point(s): In patients = 6 years of age:
• Change from baseline in FEV1 % predicted at Days 28, 56, 112, and 196;
• Change from baseline in CFQ-R Respiratory Symptoms Score (RSS) at Days 28, 56, 112, and 196.
In all patients:
• Proportion of patients with PA-negative cultures at Days 28, 56, 112 and 196;
• Use of additional (non-study) antipseudomonal antibiotics (as a marker for PA exacerbation);
• Change from baseline in weight, height, and body mass index (BMI) at Days 28, 56, 112, and 196;
In patients < 6 years of age:
• Pharmacokinetics: 1 peak plasma sample will be obtained 1 hour after the first dose of AZLI (Day 1); 1 trough plasma sample will be obtained immediately prior to the last dose of AZLI (Day 28 + 4 days). Plasma aztreonam concentrations at each time point will be summarized (mean, median, standard deviation [SD], minimum, maximum, and number of samples).

Secondary ID(s)

NCT01375049

2011-001255-36-DE

GS-US-205-0162

Source(s) of Monetary Support

Gilead Sciences, Inc.