Aztreonam Lysine for Pseudomonas Infection Eradication Study
Condition: Cystic Fibrosis
MeSH terms: Pseudomonas Infections; Cystic Fibrosis; Fibrosis
Intervention: Aztreonam for Inhalation Solution (AZLI)
Intervention description: AZLI 75 mg administered 3 times daily via the investigational eFlow® nebulizer
Intervention MeSH terms: Aztreonam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 105.0
Sex: All
Minimum age: 3 Months
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Cystic fibrosis; CF; PA; Pseudomonas aeruginosa; AZLI; aztreonam

Summary:

      This is an open-label, multi-center study in pediatric patients age 3 months to less than 18
      years with cystic fibrosis (CF) and newly detected Pseudomonas aeruginosa (PA) pulmonary
      colonization/infection. All eligible participants will be treated with a 28-day course of
      Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily. After completion of study drug,
      subjects will be followed up through Day 196 for safety and recurrence of PA.

      The primary objective is to evaluate the proportion of participants with PA-negative cultures
      at all time points during a 6-month monitoring period (through Day 196) after cessation of
      AZLI treatment. Microbiological cultures will be obtained at Baseline, Day 28 (end of AZLI
      treatment), Day 56 (1 month after completing AZLI treatment), Day 112 (3 months after
      completing AZLI treatment), and Day 196 (6 months after completing AZLI treatment).
    

Eligibility 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