An Open-Label, Randomized, Phase 3 Trial to Evaluate the Efficacy and Safety of Aztreonam for Inhalation Solution (AZLI) Versus Tobramycin Inhalation Solution (TIS) in an Intermittent Aerosolized Antibiotic Regimen in Subjects With Cystic Fibrosis Followed by an Open-Label, Single Arm Extension (European Union [EU] Only)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 274
- 主要终点
- Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted at Day 28
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
AZLI 75 mg 3 times a day (TID)
干预措施: Aztreonam for Inhalation Solution (AZLI) (Drug)
TIS 300 mg 2 times a day (BID)
干预措施: Tobramycin Inhalation Solution (TIS) (Drug)
结局指标
主要结局
Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted at Day 28
时间窗: Baseline and end of treatment Course 1 (Day 28)
Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested using an analysis of covariance (ANCOVA) model-based method.
Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses
时间窗: Baseline, and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20)
Spirometry was performed according to ATS guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the average adjusted means for the actual change in FEV1 percent predicted at Visits 4, 6, and 8 (Weeks 4, 12, and 20) was tested by mixed-effect model repeated measures (MMRM) analysis using the ITT population analysis set.
次要结局
- Relative Change From Baseline in FEV1 Percent Predicted at Day 28 in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization(Baseline and end of treatment Course 1 (Day 28))
- Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization(Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20))
- Time to Need for Intravenous (IV) Antipseudomonal Antibiotics for Respiratory Events(Day 0 to Day 168 (end of study))
- Time to First Respiratory Hospitalization(Day 0 to Day 168 (end of study))