International Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa (AIR-CF1)

This study has been completed.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00112359
First received: June 1, 2005
Last updated: March 21, 2011
Last verified: March 2011
  Purpose

The purpose of this study was to evaluate the safety and efficacy of a 28-day course of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).


Condition Intervention Phase
Cystic Fibrosis
Drug: AZLI 75 mg three times a day (TID)
Drug: Placebo three times a day (TID)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary Pseudomonas Aeruginosa (AIR-CF1)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change in CFQ-R Respiratory Symptoms Scale (RSS) Score [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]
    The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R respiratory symptoms scale (RSS; range of scores: 0-100; higher scores indicate fewer symptoms).


Secondary Outcome Measures:
  • Change in CFQ-R RSS Score [ Time Frame: Day 0 to Day 14 ] [ Designated as safety issue: No ]
    The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).

  • Change in CFQ-R RSS Score [ Time Frame: Day 0 to Day 42 ] [ Designated as safety issue: No ]
    The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).

  • Percent Change in FEV1 (L) [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]
    Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. The percent change from baseline in forced expiratory volume (liters) in one second (FEV1) was determined at Day 28.

  • Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]
    Sputum samples were collected at all participant visits of the study for analysis of microbiology endpoints. Sputum samples were processed for qualitative and quantitative culture of PA (each morphotype). Due to the skewness of the distribution of CFU data, the data were transformed using the base 10 logarithm, in an attempt to normalize the data and allow for parametric tests, before calculating changes. To account for zero values, 1 was added to each CFU measurement before being transformed. Any CFU data values where PA was not isolated from a valid culture were set to zero.

  • Number of Participants Receiving Intravenous (IV) or Inhaled Antipseudomonal Antibiotics Other Than Trial Drug [ Time Frame: Day 0 to Day 42 ] [ Designated as safety issue: No ]
    Use of IV and inhaled antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF.

  • Number of Participants Hospitalized at Least Once Between Day 0 and Day 42 [ Time Frame: Day 0 to Day 42 ] [ Designated as safety issue: No ]
    Details of all hospitalizations, including the dates of admission and discharge, were recorded on the SAE eCRF.


Enrollment: 166
Study Start Date: May 2005
Study Completion Date: April 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo three times a day (TID) Drug: Placebo three times a day (TID)
Experimental: AZLI 75 mg three times a day (TID) Drug: AZLI 75 mg three times a day (TID)

Detailed Description:

CF patients often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called Pseudomonas aeruginosa (PA). Treatment with antibiotics can stop or slow down the growth of the bacteria. The antibiotics may be given by mouth, intravenously (IV), or by inhalation as a mist. The purpose of this study was to evaluate the safety and efficacy of AZLI, an investigational formulation of the antibiotic aztreonam and administered TID using the PARI eFlow® electronic nebulizer, in CF patients with PA.

In this study, participant eligibility was assessed at a screening visit 7 to 14 days prior to the baseline visit (Day 0). Those participants who continued to meet eligibility criteria at Day 0 were randomized and began a 28-day course of blinded study treatment (AZLI TID or placebo TID). Participants returned for clinic visits at Day 14, an end of treatment visit at Day 28, and a follow-up visit 14 days after the last dose of study drug (Day 42).

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

    • Sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT);
    • Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
    • Abnormal nasal potential difference.
  • PA present in expectorated sputum or throat swab culture at Screening.
  • FEV1 between (and including) 25% and 75% predicted at Screening.
  • Negative pregnancy test at Screening.
  • Ability to perform reproducible pulmonary function tests.
  • Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.
  • Ability to provide written informed consent.

Exclusion Criteria:

  • Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes (including azithromycin) within 14 days of Screening.
  • 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.
  • Administration of any investigational drug or use of any investigational device within 28 days of Screening and within 6 half-lives of the investigational drug (whichever was longer).
  • Known local or systemic hypersensitivity to monobactam antibiotics.
  • Inability to tolerate short-acting bronchodilator use at least three times daily.
  • Changes in protocol-permitted antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days prior to Screening or between Screening and the next visit.
  • Changes in physiotherapy technique or schedule within 7 days prior to Screening or between Screening and the next visit.
  • History of lung transplantation.
  • A chest x-ray indicating abnormal findings at Screening or within the previous 90 days.
  • Abnormal renal or hepatic function at Screening.
  • 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.
  • Use of aerosolized hypertonic saline (except for sputum induction) during the 14 days preceding Visit 1.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112359

  Show 53 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Bruce Montgomery, MD Corus Pharma, Inc.
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mark Bresnik, MD, Director, Clinical Research, Gilead Sciences, Inc.
ClinicalTrials.gov Identifier: NCT00112359     History of Changes
Other Study ID Numbers: CP-AI-007
Study First Received: June 1, 2005
Results First Received: September 10, 2010
Last Updated: March 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Cystic Fibrosis
Pseudomonas aeruginosa
Pulmonary Cystic Fibrosis

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on September 18, 2014