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

July 13, 2012
April 6, 2016
December 2012
January 2015   (final data collection date for primary outcome measure)
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.
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Complete list of historical versions of study NCT01641822 on ClinicalTrials.gov Archive Site
  • 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.
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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
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
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.
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Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Cystic Fibrosis
  • Drug: AZLI
    Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily combined with diluent administered using an eFlow nebulizer
    Other Name: Cayston®
  • 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®
  • 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.
    Interventions:
    • Drug: AZLI
    • Drug: Tobramycin inhalation solution
  • 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.
    Interventions:
    • Drug: Placebo to match AZLI
    • Drug: Tobramycin inhalation solution
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
107
January 2015
January 2015   (final data collection date for primary outcome measure)

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
Both
6 Years and older   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01641822
GS-US-205-0170, 2015-000398-11
Yes
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Gilead Sciences
Gilead Sciences
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Study Director: Mark Bresnik, MD Gilead Sciences
Gilead Sciences
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP