Aztreonam for Inhalation Solution vs Tobramycin Inhalation Solution in Patients With Cystic Fibrosis & Pseudomonas Aeruginosa

Gilead Sciences

Status and phase

Completed

Phase 3

Conditions

Cystic Fibrosis

Treatments

Drug: Tobramycin Inhalation Solution (TIS)

Drug: Aztreonam for Inhalation Solution (AZLI)

Study type

Interventional

Funder types

Industry

Identifiers

NCT00757237

GS-US-205-0110

Details and patient eligibility

About

The purpose of this study was to assess the comparative safety and effectiveness of aztreonam for inhalation solution versus tobramycin inhalation solution in adult and pediatric patients with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection.

Full description

Number of Subjects Planned: Approximately 240 randomized patients

Target Population: CF patients >= 6 years of age with stable pulmonary disease, who at study entry had a recent positive sputum culture for PA and had been previously treated with aerosolized antibiotics without demonstration of drug intolerance.

The randomized phase of this study, used for hypotheses testing, enrolled participants from both the United States (US) and EU. An open-label, single-arm extension was available for participants in the EU who completed at least one course of AZLI or TIS during the randomized portion of the study. These participants were eligible to receive 3 additional cycles of AZLI in a 28-day, intermittent, repeating treatment regimen. Results of the extension phase will be available the first quarter (Q1) of 2012.

Randomized Phase Study Design (US and EU): This was an open-label, multicenter, randomized, parallel group study. The study design consisted of 2 treatment arms of 28-day, intermittent, repeating treatment regimens: aztreonam for inhalation solution (AZLI) or tobramycin inhalation solution (TIS). The total study period was 26 weeks. The study schedule included 9 visits - Screening, Baseline, Day 14, Day 28, followed by visits every 28 days through the end of the study.

Enrollment

274 patients

Sex

All

Ages

6+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Males or females aged 6 years and older
Subjects with CF as diagnosed by one of the following: documented sweat chloride >= 60 mEq/L by quantitative pilocarpine iontophoresis test, or documented sweat sodium >= 60 mmol/L, or 2 well characterized genetic mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, or abnormal nasal potential difference with accompanying symptoms characteristic of CF
Documented PA in an expectorated sputum or throat swab culture within 3 months prior to Visit 1 or at Visit 1
Subjects must be able to provide written informed consent/assent prior to any study related procedures; parent/guardian must be able to give written informed consent as necessary prior to any study related procedure
Subjects must have received previous treatment with aerosolized antibiotics without demonstration of drug intolerance
FEV1 <= 75% predicted at Visit 1
Ability to perform reproducible pulmonary function tests
Chest radiograph at Visit 1 without significant acute findings (eg, infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax); or chest radiograph or magnetic resonance image (MRI) obtained within the 180 days prior to Visit 1 without acute findings and no significant intercurrent illness; chronic, stable findings (eg, chronic scarring or atelectasis) are allowed

Exclusion criteria

Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day
History of sputum or throat swab culture yielding B. cepacia in the previous 2 years
Current requirement for daily continuous oxygen supplementation or requirement for more than 2 L/minute at night
Administration of any investigational drug or device within 28 days of Visit 1 or within 6 half-lives of the investigational drug (whichever is longer)
Known local or systemic hypersensitivity to monobactam antibiotics
Known allergies/intolerance to tobramycin
Inability to tolerate inhalation of a short acting beta agonist
Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1
Administration of antipseudomonal antibiotics by inhalation, intravenous or oral routes within the 14 days prior to Randomization/Visit 2
Changes in antimicrobial, bronchodilator (BD), dornase alfa, or corticosteroid medications within 7 days prior to Visit 1
Changes in physiotherapy technique or schedule within 7 days prior to Visit 1
History of lung transplantation
Abnormal renal or hepatic function or serum chemistry at Visit 1, defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 5 times upper limit of normal range (ULN) or creatinine > 2 times ULN
Positive pregnancy test at Visit 1; all women of childbearing potential will be tested
Female of childbearing potential who is lactating or is not (in the opinion of the investigator) practicing an acceptable method of birth control; female subjects who utilize hormonal contraceptives as one of their birth control methods must have used the same method for at least 3 months before study dosing
Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or compliance with the protocol