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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Gilead Sciences
- Enrollment
- 107
- Locations
- 71
- Primary Endpoint
- Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 6 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: AZLI (Drug)
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.
Intervention: Tobramycin inhalation solution (Drug)
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.
Intervention: Placebo to match AZLI (Drug)
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.
Intervention: Tobramycin inhalation solution (Drug)
Outcomes
Primary Outcomes
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)
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 Outcomes
- 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)
- 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))
- 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)
- 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))