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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01641822
First received: July 13, 2012
Last updated: April 6, 2016
Last verified: April 2016
  Purpose
The primary objective of this study is to evaluate the safety and efficacy of a CAT regimen with aztreonam for inhalation solution (AZLI) and tobramycin inhalation solution (TIS) in adult and pediatric subjects with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection. Participants will be enrolled in a 28 day TIS run-in phase, and will be eligible for randomization in the comparative phase if they have not received non-study oral antibiotics for a respiratory event, or IV or inhaled antibiotics for any indication between Visits 2 and 3, have not developed a condition requiring hospitalization or other change in clinical status which, in the opinion of the investigator would preclude their ability to continue in the study, and have demonstrated at least 50% TIS compliance. Participants enrolled in the comparative phase will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI or placebo for 28 days followed by TIS for 28 days.

Condition Intervention Phase
Cystic Fibrosis
Drug: AZLI
Drug: Placebo to match AZLI
Drug: Tobramycin inhalation solution
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 (PDE) From Baseline Through Week 24 [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ] [ Designated as safety issue: No ]
    PDEs were characterized by a change or worsening from baseline of 1 or more documented signs or symptoms (decreased exercise tolerance, increased cough, increased sputum or chest congestion, decreased appetite, or other signs or symptoms) associated with the use of non-study IV or inhaled antibiotics and be verified by a blinded independent adjudication committee.


Secondary Outcome Measures:
  • Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20) [ Time Frame: Comparative Phase: Baseline and 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. The adjusted mean is from a mixed-effect model repeated measures (MMRM) analysis. The model includes terms for baseline value, previous exacerbations (1, 2, ≥ 3), treatment, visit (categorical), and treatment by visit interaction.

  • Percentage of Participants Who Used Non-study IV or Inhaled Antibiotics for PDEs [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ] [ Designated as safety issue: No ]
  • Time to First Protocol-defined Pulmonary Exacerbation [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ] [ Designated as safety issue: No ]
    The time to first protocol-defined pulmonary exacerbation was calculated using the Kaplan-Meier method.

  • Rate of Hospitalizations for a Respiratory Event [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ] [ Designated as safety issue: No ]
    The rate of hospitalizations for a respiratory event per participant year was calculated using negative binomial regression analysis.

  • Average Change From Baseline in the CFQ-R Respiratory Symptom Scale (RSS) Score Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20) [ Time Frame: Comparative Phase: Baseline and Weeks 4, 12 and 20 ] [ Designated as safety issue: No ]
    Respiratory symptoms (eg, coughing, congestion, wheezing) were assessed with the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS). The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms. The adjusted mean is from a mixed-effect model repeated measures (MMRM) analysis. The model includes terms for baseline value, previous exacerbations (1, 2, ≥ 3), treatment, visit (categorical), and treatment by visit interaction.


Enrollment: 107
Study Start Date: December 2012
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AZLI
Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI for 28 days followed by TIS for 28 days.
Drug: AZLI
Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily combined with diluent administered using an eFlow nebulizer
Other Name: Cayston®
Drug: Tobramycin inhalation solution
Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
Other Name: TOBI®
Placebo Comparator: Placebo
Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: placebo to match AZLI for 28 days followed by TIS for 28 days.
Drug: Placebo to match AZLI
Placebo to match AZLI 3 times daily combined with diluent administered using an eFlow nebulizer
Drug: Tobramycin inhalation solution
Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
Other Name: TOBI®

  Eligibility

Ages Eligible for Study:   6 Years and older   (Child, Adult, Senior)
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
  • Forced expiratory volume (FEV)1 ≥ 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

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01641822     History of Changes
Other Study ID Numbers: GS-US-205-0170  2015-000398-11 
Study First Received: July 13, 2012
Results First Received: January 15, 2016
Last Updated: April 6, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 26, 2016