Clinical trial NCT00128492: Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis (CF) Patients With Pseudomonas Aeruginosa (PA)
Official title: A Phase 3, Open-label, Follow-On Study of Multiple Courses of Aztreonam Lysinate for Inhalation (AI) in Cystic Fibrosis Patients (AIR-CF3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
Pseudomonas aeruginosa
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2005-08-10
Enrollment: 274
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the safety and efficacy of multiple courses of AZLI in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).

Detailed description: People with CF often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by PA. Treatment with antibiotics is used to reduce the presence of the bacteria. The antibiotics may be given orally, intravenously, or inhaled as a mist. The purpose of this study was to evaluate whether AZLI, an investigational formulation of the antibiotic aztreonam, is safe in repeated courses in patients with CF and PA.

A course of AZLI treatment in this study comprised 28 days, followed by a 28-day period off treatment. Participants could receive up to 9 courses of AZLI, with a total time on study of up to 18 months. Safety and efficacy results for the 18-month, 9-course period are reported, with efficacy results presented on a by-treatment course basis.

Eligibility criteria: Inclusion Criteria:

* Compliance with Studies CP-AI-005 (NCT00104520) or CP-AI-007 (NCT00112359) by taking at least 50% of expected study medication.
* Completion of CP-AI-005 or CP-AI-007 or was withdrawn due to need for antipseudomonal antibiotics or for an AE unrelated to study medication tolerance.
* Ability to provide written informed consent/assent prior to initiation of study-related procedures.
* Ability to perform reproducible pulmonary function tests.

Exclusion Criteria:

* Use of any investigational medication or device between the last visit of CP-AI-005 or CP-AI-007 and Visit 1 of this study.
* Concurrent participation in a study of another investigational drug or device.
* Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day.
* History of sputum or throat swab culture yielding Burkholderia cepacia in the previous 2 years.
* History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
* Inability to tolerate study medication in CP-AI-005 or CP-AI-007.
* Known local or systemic hypersensitivity to aztreonam.
* Inability to tolerate inhalation of a short acting beta-2 agonist.
* Abnormal renal or hepatic function based on results of most recent test.
* Female of child-bearing potential who was pregnant, lactating, or not (in the opinion of the investigator) practicing an acceptable method of birth control.
* Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would have interfered with participant treatment, assessment, or compliance with the protocol.

Primary outcomes:
measure: Number of Participants Reporting Adverse Events (AEs)
timeFrame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
measure: Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI
timeFrame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
measure: Change in Heart Rate (HR)
timeFrame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
measure: Change in Systolic and Diastolic Blood Pressure (BP)
timeFrame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
measure: Change in Temperature
timeFrame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
measure: Change in Respiratory Rate (RR)
timeFrame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
measure: Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets
timeFrame: Baseline and end of Course 9 (Week 68)
measure: Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Hematology - Number of Red Blood Cells (RBC)
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Hematology - Hematocrit
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Hematology - Hemoglobin
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Hematology - Mean Corpuscular Volume (MCV)
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Hematology - Mean Corpuscular Hemoglobin (MCH)
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC)
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT)
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Chemistry - Concentration of Chloride, Potassium, and Sodium
timeFrame: Baseline and end of treatment Course 9 (Week 68)
measure: Serum Chemistry - Concentration of Total Protein
timeFrame: Baseline and end of treatment Course 9 (Week 68)
Secondary outcomes:
measure: Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum
timeFrame: Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
measure: Number of Participants With Other Pathogens
timeFrame: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)
measure: Minimum Inhibitory Concentration (MIC) of Aztreonam
timeFrame: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)
measure: Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75)
timeFrame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
measure: Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS)
timeFrame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
measure: Time to First Hospitalization Due to a Respiratory Event
timeFrame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
measure: Change in Body Weight
timeFrame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
measure: Missed School/Work Days Due to CF Symptoms
timeFrame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
measure: Time to Intravenous (IV) Antipseudomonal Antibiotics
timeFrame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Other outcomes:
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city: Phoenix
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city: La Jolla
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state: California
city: Los Angeles
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state: California
city: Oakland
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state: California
city: Orange
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state: California
city: Denver
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state: Colorado
city: Hartford
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state: Connecticut
city: New Haven
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state: Connecticut
city: Jacksonville
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state: Florida
city: Orlando
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state: Florida
city: Atlanta
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state: Georgia
city: Augusta
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state: Georgia
city: Chicago
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state: Illinois
city: Glenview
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state: Illinois
city: Maywood
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state: Illinois
city: Park Ridge
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state: Illinois
city: Indianapolis
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state: Indiana
city: Wichita
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state: Kansas
city: Shreveport
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state: Louisiana
city: Boston
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state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
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state: Michigan
city: Minneapolis
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state: Minnesota
city: Columbia
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state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Livingston
country: United States
state: New Jersey
city: Morristown
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Brooklyn
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state: New York
city: Buffalo
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Portsmouth
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Westmead
country: Australia
state: New South Wales
city: Herston
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Prahan
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Perth
country: Australia
state: Western Australia
city: Edmonton
country: Canada
state: Alberta
city: London
country: Canada
state: Ontario
city: Auckland
country: New Zealand
Study officials:
affiliation: Gilead Sciences
name: Bruce Montgomery, MD
role: STUDY_DIRECTOR
References: