A Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysine For Inhalation in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa (AIR-CF4)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 39
- 主要终点
- Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28
研究概览
简要总结
The purpose of this study was to evaluate the safety and efficacy of a 28-day course of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF), mild lung disease (forced expiratory volume in 1 second [FEV1] >75% predicted, and Pseudomonas aeruginosa (PA) infection.
详细描述
CF patients often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called Pseudomonas aeruginosa (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 AZLI, an investigational formulation of the antibiotic aztreonam and administered three times a day using the PARI eFlow® electronic nebulizer, in CF patients with PA and mild lung disease.
In this study, participant eligibility was assessed at a screening visit that occurred up to 14 days prior to the baseline visit (Day 0). Those participants who met eligibility criteria at Day 0 were randomized and began a 28-day course of blinded study treatment (AZLI or placebo TID). Participants returned for clinic visits at Day 14, an end of treatment visit at Day 28, and a follow up visit 14 days after the last dose of the trial drug (Day 42).
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
- •Participants ≥ 6 years of age
- •Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
- •Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test
- •Two well characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
- •Abnormal nasal potential difference
- •PA present in expectorated sputum or throat swab culture at Visit 1 OR documented PA in 2 expectorated sputum or throat swab cultures within the 12 months prior to Visit 1 (one of the previous PA positive cultures must have been no more than 3 months prior to Visit 1)
- •FEV1 > 75% predicted at Visit 1
- •Participants must have exhibited two or more of the following chronic and/or intermittent CF symptoms, for a minimum of 28 days prior to randomization and with no worsening of symptoms within 7 days prior to randomization:
- •Chest congestion
- •Daily cough
- •Productive cough
- •Trouble breathing
- •Nocturnal wakening due to coughing
- •Participants (and parent/guardian as required) had to be able to provide written informed consent/assent prior to any study related procedures
- •Females of childbearing potential had to have a negative urine pregnancy test at Visit 1
- •Ability to perform reproducible pulmonary function tests
- •In the opinion of the Investigator, the participant did not require immediate antipseudomonal antibiotic intervention to treat an impending exacerbation, and the participant's condition was stable enough to enroll in the study
排除标准
- •Administration of any investigational drug or device within 28 days prior to Visit 1 or within 6 half-lives of the investigational drug (whichever was longer)
- •Administration of any IV, oral, or inhaled antipseudomonal antibiotic within 28 days prior to Visit 1
- •Known local or systemic hypersensitivity to monobactam antibiotics
- •Inability to tolerate short-acting bronchodilator (BD) use at least TID
- •Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1
- •Changes in or initiation of chronic hypertonic saline treatment within 28 days prior to Visit 1
- •Changes in or initiation of dornase alfa within 28 days prior to Visit 1
- •Changes in antimicrobial, BD, 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
- •History of participation (enrollment) in any prior clinical studies with AZLI
- •A chest radiograph at Visit 1 (or within the previous 180 days of Visit 1), with abnormalities indicating a significant acute finding (e.g., lobar infiltrate and atelectasis, pneumothorax, or pleural effusion); a chest radiograph obtained and interpreted between Visits 1 and 2 was also acceptable for determining eligibility
- •Positive urine pregnancy test at Visit 1; all women of childbearing potential were to be tested
- •Females of childbearing potential who were lactating or were not (in the opinion of the investigator) practicing an acceptable method of birth control; female participants who utilized hormonal contraceptives as their birth control method must have used the same method for at least 3 months before study dosing
- •Participant was being assessed at Visit 1 by the investigator for an acute change in respiratory symptoms
- •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 three times daily (TID)
干预措施: Placebo three times daily (TID) (Drug)
AZLI 75 mg three times daily (TID)
干预措施: AZLI 75 mg three times daily (TID) (Drug)
结局指标
主要结局
Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28
时间窗: Day 0 to Day 28
The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.
次要结局
- Change From Baseline in CFQ-R RSS Score at Day 14(Day 0 to Day 14)
- Change From Baseline in CFQ-R RSS Score at Day 42(Day 0 to Day 42)
- Change From Baseline in CFQ-R Physical Functioning Domain Score(Day 0 to Day 28)
- Number of Participants Using Additional (Nonprotocol-specified) Antipseudomonal Antibiotics During Study(Day 0 to Day 42)
- Number of Participants Hospitalized During Study(Day 0 to Day 42)
- Change From Baseline in Log10 Pseudomonas Aeruginosa (PA) Colony Forming Units (CFUs) in Sputum at Day 28(Day 0 to Day 28)
- Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted(Day 0 to Day 28)