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

Phase 3

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: Placebo to match AZLI
Drug: AZLI
Drug: Tobramycin inhalation solution

Registration Number: NCT01641822

Lead Sponsor: Gilead Sciences

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 107

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Tobramycin inhalation solution	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.
AZLI	Tobramycin inhalation solution	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.
Placebo	Placebo to match AZLI	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.
AZLI	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.

Primary Outcome Measures

Name	Time	Method
Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24	Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)	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

Name	Time	Method
Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)	Comparative Phase: Baseline and 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.
Percentage of Participants Who Used Non-study IV or Inhaled Antibiotics for PDEs	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	Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)	The time to first protocol-defined pulmonary exacerbation was calculated using the Kaplan-Meier method.
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)	Comparative Phase: Baseline and 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.
Rate of Hospitalizations for a Respiratory Event	Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)	The rate of hospitalizations for a respiratory event per participant year was calculated using negative binomial regression analysis.

Trial Locations

Locations (71): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Phoenix Children's Hospital
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Phoenix, Arizona, United States
University of California - San Diego
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La Jolla, California, United States
Children's Hospital Los Angeles
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Los Angeles, California, United States
Kaiser Permanente Medical Center
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Oakland, California, United States
National Jewish Health
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Denver, Colorado, United States
Alfred I. duPont Hospital for Children
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Wilmington, Delaware, United States
Children's National Medical Center
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Washington DC, District of Columbia, United States
Central Florida Pulmonary Group
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Altamonte Springs, Florida, United States
University of Florida
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Gainesville, Florida, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States