Aztreonam Lysine for Pseudomonas Infection Eradication Study

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01375049
• Date of registration: 15/06/2011
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences
• Public title: Aztreonam Lysine for Pseudomonas Infection Eradication Study ALPINE
• 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)
• Date of first enrolment: August 2011
• Target sample size: 105
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01375049
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: Mark Bresnik, MD
• Affiliation: Gilead Sciences

Key inclusion & exclusion criteria

Inclusion Criteria:

- Males or females age 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 (e.g., throat swab,
sputum, or BAL) for PA within 30 days of study entry (prior to 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)

- Forced expiratory volume in 1 second (FEV1) = 80% predicted at screening visit
(subjects = 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 have
required administration of IV antipseudomonal antibiotics, oxygen supplementation, or
hospitalization.

- All sexually active females who were 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.

- Males 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

- Participants and/or parent/guardian must be able to give written informed consent
prior to any study related procedure

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 beta 2 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 participants
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:

- Aspartate aminotransferase (AST) or alanine aminotransferase (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
females 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 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: 3 Months
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Aztreonam for Inhalation Solution (AZLI)

Primary Outcome(s)

Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Sensitivity Analysis Set) [Time Frame: Day 28 to Day 196]

Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Evaluable Analysis Set) [Time Frame: Day 28 to Day 196]

Secondary Outcome(s)

Change From Baseline in Body Mass Index (BMI) [Time Frame: Baseline to Days 28, 56, 112, and 196]

Change From Baseline in Height [Time Frame: Baseline to Days 28, 56, 112, and 196]

Percentage of Participants With PA-negative Cultures [Time Frame: Days 28, 56, 112, and 196]

Change From Baseline in CFQ-R RSS Score [Time Frame: Baseline to Days 28, 56, 112, and 196]

Pharmacokinetics (PK) Peak and Trough Plasma Concentrations of Aztreonam [Time Frame: Day 1 (1 hour postdose) and Day 28 (immediately prior to dosing)]

Change From Baseline in FEV1% Predicted [Time Frame: Baseline to Days 28, 56, 112, and 196]

Change From Baseline in Weight [Time Frame: Baseline to Days 28, 56, 112, and 196]

Use of Additional (Non-study) Antipseudomonal Antibiotics [Time Frame: Baseline to Day 196]

Secondary ID(s)

GS-US-205-0162

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 01/07/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01375049