A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial With Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary P. Aeruginosa Requiring Frequent Antibiotics (AIR-CF2)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 211
- 试验地点
- 56
- 主要终点
- Time to Need for Inhaled or Intravenous (IV) Antipseudomonal Antibiotics
研究概览
简要总结
The purpose of this study was to evaluate the safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).
详细描述
Patients with CF often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called PA. Treatment with antibiotics can stop or slow down the growth of the bacteria. The antibiotics may be given by mouth, intravenously (IV), or by inhalation as a mist. The purpose of this study was to evaluate the safety and efficacy of aztreonam for inhalation solution (AZLI), an investigational formulation of the antibiotic administered using the eFlow® Electronic Nebulizer by PARI GmbH, in CF patients with PA.
In this study, participants were screened for eligibility at Visit 1 (Day -42) and returned to the center for Visit 2 after a 14-day evaluation period. At Visit 2 (Day -28), participants began a 28-day course of open-label Tobramycin Inhalation Solution (TIS). At Visit 3 (Day 0), following completion of the 28-day course of TIS, participants began randomized, blinded treatment with either AZLI twice a day (BID) or three times a day (TID) or placebo BID or TID, and continued treatment for a total of 28 days, with a clinic visit at Day 14 (Visit 4) and at the end of treatment (Visit 5 [Day 28]). Participants returned for visits every 2 weeks for 8 weeks after the end of the blinded treatment (Visits 6 to 9 [Days 42 to 84]).
Two hundred and forty-seven participants were treated in the TIS phase of this study. Two hundred and eleven subjects completed the TIS phase and were treated in the placebo-controlled phase with study drug (AZLI or placebo).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •CF as diagnosed by:
- •Documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test; or
- •Two well-characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
- •Abnormal nasal potential difference with accompanying symptoms characteristic of CF.
- •PA present in expectorated sputum or throat swab culture at Screening.
- •Participants must have received three or more courses of TIS within the previous 12 months.
- •Participants on chronic azithromycin must have had no change in regimen in the previous 3 months and must have had a need for TIS and/or additional antipseudomonal therapy since initiation of azithromycin.
- •Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75% predicted at Screening.
- •Ability to perform reproducible pulmonary function tests.
- •Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.
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 culture swab yielding Burkholderia cepacia in the past 2 years.
- •History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
- •Administration of any investigational drug or device within 28 days of Screening (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).
- •Known local or systemic hypersensitivity to monobactam antibiotics.
- •Inability to tolerate inhalation of a short acting Beta-2 agonist.
- •Changes in antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days before Screening or between Screening and the next visit.
- •Changes in physiotherapy technique or schedule within 7 days before Screening or between Screening and the next visit.
- •History of lung transplantation.
- •A chest X-ray indicating abnormal findings at Screening or within the previous 90 days.
- •Abnormal renal or hepatic function or serum chemistry at Screening (aspartate aminotransferase [AST], alanine aminotransferase [ALT] greater than 5 times the upper limit of normal range; Creatinine greater than 2 times the upper limit of normal range).
- •Positive pregnancy test at Screening.
- •Female of childbearing potential who was lactating or in the opinion of the investigator was not practicing acceptable birth control.
- •Any serious or active medical or psychiatric illness, which in the opinion of the investigator would have interfered with participant treatment, assessment, or compliance with the protocol.
研究组 & 干预措施
Placebo (pooled two times a day [BID]/three times a day [TID])
干预措施: Placebo two times a day (BID)/three times a day (TID) (Drug)
AZLI (pooled two times a day [BID]/three times a day [TID])
干预措施: AZLI 75 mg two times a day (BID)/three times a day (TID) (Drug)
结局指标
主要结局
Time to Need for Inhaled or Intravenous (IV) Antipseudomonal Antibiotics
时间窗: Day 0 to Day 84 (end of study)
The primary endpoint was time to need for a course of inhaled or IV antipseudomonal antibiotics with documented physician assessment of need for antibiotics. Antipseudomonal Antibiotic need was documented based on the presence of at least one of the following four symptoms predictive of pulmonary exacerbation: decreased exercise tolerance, increased cough, increased sputum / chest congestion, decreased appetite, or other.
次要结局
- Change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score(Day 0 to Day 28)
- Percent Change in Forced Expiratory Volume in 1 Second (FEV1) (L)(Day 0 to Day 28)
- Number of Hospitalization Days(Day 0 to Day 84)
- Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum(Day 0 to Day 28)