Phase 3 Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy Regimen for the Treatment of Chronic Pseudomonas Aeruginosa Infection in Patients With CF (AZLI CAT)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01641822
First received: July 13, 2012
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

This study is to investigate whether using a continuous alternating therapy (CAT) regimen of 2 antibiotics of different classes and with different mechanisms of action may provide the clinical benefits of reducing acute pulmonary exacerbations, maintaining lung function, and controlling respiratory symptoms for cystic fibrosis (CF) patients while minimizing the risk of emergence of antibiotic-resistant Pseudomonas aeruginosa (PA) strains.

After screening, eligible participants will be enrolled into the study and begin a 28-day run in period of tobramycin inhalation solution (TIS) twice daily. After the run-in, participants will return to the clinic and be randomized to either the Aztreonam for Inhalation Solution (AZLI) arm or the placebo arm. The AZLI arm has 3 cycles of AZLI three times daily for 28 days alternating with TIS twice daily for 28 days. The placebo arm has 3 cycles of placebo three times daily for 28 days alternating with 3 cycles of TIS twice daily for 28 days. Participants will return to the clinic for evaluation after each cycle of antibiotics for evaluation. There will be 9 scheduled study visits per participant.


Condition Intervention Phase
Cystic Fibrosis
Drug: Aztreonam for Inhalation Solution (AZLI)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy (CAT) Regimen of Inhaled Antibiotics for the Treatment of Chronic Pulmonary Pseudomonas Aeruginosa Infection in Subjects With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Rate of protocol-defined exacerbations from baseline through Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Average actual change from baseline in forced expiratory volume in 1 second (FEV1) % predicted at the end of each course of study drug [ Time Frame: Weeks 4, 12 and 20 ] [ Designated as safety issue: No ]
    FEV1 % predicted is defined as FEV1 % of the patient divided by the average FEV1 % in the population for any person of similar age, sex and body composition.

  • Time to first protocol-defined pulmonary exacerbation [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The time to first protocol-defined pulmonary exacerbation will be summarized using Kaplan-Meier (KM) summary statistics and analyzed using the log-rank test.

  • Rate of hospitalizations for a respiratory event [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The rate of respiratory hospitalizations will be summarized and analyzed using negative binomial regression methods similar to the primary endpoint analysis. Total number of events will also be presented.

  • Average change from baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Symptom Scale (RSS) score at the end of each course of study drug (Weeks 4, 12, and 20) [ Time Frame: Baseline to Weeks 4, 12, and 20 ] [ Designated as safety issue: No ]
  • Percent of subjects who use non-study IV or inhaled antibiotics for protocol-defined pulmonary exacerbations through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: November 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aztreonam for Inhalation Solution (AZLI) Drug: Aztreonam for Inhalation Solution (AZLI)
75 mg (1 ml) of aztreonam, supplied as Aztreonam for Inhalation Solution (AZLI) administered three times a day for 28 days per course.
Other Name: Cayston
Placebo Comparator: Sugar solution for inhalation Drug: Placebo
Sugar solution for inhalation administered three times a day for 28 days per course.

  Eligibility

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

Inclusion Criteria:

  • Confirmed diagnosis of CF
  • Presence of PA in 2 lower respiratory tract cultures in the 12 months prior to screening
  • FEV1 ≥25 and ≤ 75% predicted
  • History of 1 hospitalization or 1 course of IV antibiotics for an acute respiratory exacerbation in the 12 months prior to screening

Exclusion Criteria:

  • Concurrent use of oral, IV or inhaled antibiotics at enrollment
  • Concurrent hospitalization at enrollment
  • History of local or systemic hypersensitivity to monobactams or aminoglycoside antibiotics or history of aminoglycoside antibiotic associated toxicity
  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: NCT01641822

  Show 71 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Mark Bresnik, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01641822     History of Changes
Other Study ID Numbers: GS-US-205-0170
Study First Received: July 13, 2012
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pseudomonas Infections
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Gram-Negative Bacterial Infections
Bacterial Infections
Aztreonam
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014