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

Gilead Sciences107 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

107

Conditions

Cystic Fibrosis

Interventions

Eligibility

Sex: ALLMin age: 6 Years

Medical Language ↔ Plain English

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

Locations (71)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Phoenix Children's Hospital

Phoenix, Arizona, United States

University of California - San Diego

La Jolla, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Kaiser Permanente Medical Center

Oakland, California, United States

Outcomes

Primary Outcomes

Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24

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.

Time frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)

Secondary Outcomes

Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)

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.

Time frame: Comparative Phase: Baseline and Weeks 4, 12 and 20

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)

Time to First Protocol-defined Pulmonary Exacerbation

The time to first protocol-defined pulmonary exacerbation was calculated using the Kaplan-Meier method.

Time frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)

Rate of Hospitalizations for a Respiratory Event

The rate of hospitalizations for a respiratory event per participant year was calculated using negative binomial regression analysis.

Time frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)

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)

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.

Time frame: Comparative Phase: Baseline and Weeks 4, 12 and 20