Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis (CF) Patients With Pseudomonas Aeruginosa (PA)

NCT00128492 | Completed Phase 3 Results DMC

• 1 other identifier: CP-AI-006
• Study Type: interventional
• Target: 274
• Locations: 4 countries
• Sites: 65

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).

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; Pseudomonas aeruginosa

Outcome Measures

Primary Outcomes (18)

• Number of Participants Reporting Adverse Events (AEs)

  Participants experiencing at least 1 treatment-emergent AE or at least 1 serious adverse event (SAE) were summarized for the study as a whole. A treatment-emergent AE was any physical or clinical worsening in symptoms or disease experienced by the participant, whether or not the event was considered related to study participation or study procedures. An SAE was any adverse experience that resulted in hospitalization or death. Participants were monitored for AEs and SAEs during all on-treatment and off-treatment intervals throughout the 18-month study period.

  Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

• 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

  Airway reactivity (percent change in FEV1 from pretreatment to 30 minutes after treatment with AZLI) was assessed at all study visits in which a participant received AZLI treatment. A participant was included in this endpoint if they experienced a decline in FEV1 of ≥15% at any visit in which they received AZLI.

  Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug

• Change in Heart Rate (HR)

  HR was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.

  Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

• Change in Systolic and Diastolic Blood Pressure (BP)

  BP was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.

  Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

• Change in Temperature

  Temperature was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.

  Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

• Change in Respiratory Rate (RR)

  RR was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.

  Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)

• Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets

  Baseline and end of Course 9 (Week 68)

• Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils

  Baseline and end of treatment Course 9 (Week 68)

• Serum Hematology - Number of Red Blood Cells (RBC)

  Baseline and end of treatment Course 9 (Week 68)

• Serum Hematology - Hematocrit

  Baseline and end of treatment Course 9 (Week 68)

• Serum Hematology - Hemoglobin

  Baseline and end of treatment Course 9 (Week 68)

• Serum Hematology - Mean Corpuscular Volume (MCV)

  Baseline and end of treatment Course 9 (Week 68)

• Serum Hematology - Mean Corpuscular Hemoglobin (MCH)

  Baseline and end of treatment Course 9 (Week 68)

• Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC)

  Baseline and end of treatment Course 9 (Week 68)

• Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT)

  Baseline and end of treatment Course 9 (Week 68)

• Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen

  Baseline and end of treatment Course 9 (Week 68)

• Serum Chemistry - Concentration of Chloride, Potassium, and Sodium

  Baseline and end of treatment Course 9 (Week 68)

• Serum Chemistry - Concentration of Total Protein

  Baseline and end of treatment Course 9 (Week 68)

Secondary Outcomes (9)

• Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum

  Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

• Number of Participants With Other Pathogens

  Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)

• Minimum Inhibitory Concentration (MIC) of Aztreonam

  Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)

• Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75)

  Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

• Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS)

  Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)

Interventions

AZLI 75 mg two times a day (BID)/ three times a day (TID) DRUG

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (65)

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Birmingham, Alabama, United States

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Anchorage, Alaska, United States

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Phoenix, Arizona, United States

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Little Rock, Arkansas, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Oakland, California, United States

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Orange, California, United States

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Denver, Colorado, United States

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Hartford, Connecticut, United States

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New Haven, Connecticut, United States

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Jacksonville, Florida, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Chicago, Illinois, United States

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Glenview, Illinois, United States

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Maywood, Illinois, United States

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Park Ridge, Illinois, United States

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Indianapolis, Indiana, United States

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Wichita, Kansas, United States

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Shreveport, Louisiana, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Columbia, Missouri, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Livingston, New Jersey, United States

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Morristown, New Jersey, United States

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Albany, New York, United States

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Brooklyn, New York, United States

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Buffalo, New York, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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Syracuse, New York, United States

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Valhalla, New York, United States

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Chapel Hill, North Carolina, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Dayton, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Hershey, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Columbia, South Carolina, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Portsmouth, Virginia, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Westmead, New South Wales, Australia

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Herston, Queensland, Australia

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Adelaide, South Australia, Australia

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Prahan, Victoria, Australia

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Nedlands, Western Australia, Australia

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Perth, Western Australia, Australia

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Edmonton, Alberta, Canada

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London, Ontario, Canada

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Auckland, New Zealand

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MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Interventions

BID protein, human

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Limitations and Caveats

Descriptive statistics for all participants receiving 1 or more doses of AZLI were summarized for the safety, microbiology, and efficacy endpoints. No formal hypothesis tests were planned. Rates of AEs and SAEs are not adjusted for time on study.

Results Point of Contact

• Title: Mark Bresnik, Director of Clinical Research
• Organization: Gilead Sciences, Inc.

Mark.Bresnik@gilead.com

650-522-5934

Study Officials

• Bruce Montgomery, MD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 8, 2005
• First Posted: August 10, 2005
• Study Start: August 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: January 1, 2009
• Last Updated: May 19, 2011
• Results First Posted: March 11, 2011

Record last verified: 2011-05

Locations

US (56); CA (2); AU (6); NZ (1)