Open-Label Phase 2 Trial to Evaluate the Safety and Efficacy of Aztreonam 75 mg Powder and Solvent for Nebuliser Solution/Aztreonam for Inhalation Solution (AZLI) in Pediatric Patients With Cystic Fibrosis (CF) and New Onset Lower Respiratory Tract Culture Positive for Pseudomonas Aeruginosa (PA)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 58
- 主要终点
- Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Evaluable Analysis Set)
研究概览
简要总结
This is an open-label, multi-center study in pediatric patients age 3 months to less than 18 years with cystic fibrosis (CF) and newly detected Pseudomonas aeruginosa (PA) pulmonary colonization/infection. All eligible participants will be treated with a 28-day course of Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily. After completion of study drug, subjects will be followed up through Day 196 for safety and recurrence of PA.
The primary objective is to evaluate the proportion of participants with PA-negative cultures at all time points during a 6-month monitoring period (through Day 196) after cessation of AZLI treatment. Microbiological cultures will be obtained at Baseline, Day 28 (end of AZLI treatment), Day 56 (1 month after completing AZLI treatment), Day 112 (3 months after completing AZLI treatment), and Day 196 (6 months after completing AZLI treatment).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females age 3 months to less than 18 years
- •Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:
- •Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR
- •Abnormal nasal transepithelial potential difference test OR
- •Two well-characterized, disease-causing genetic mutations in the CF transmembrane conductance regulator (CFTR) gene AND
- •One or more clinical features consistent with CF
- •Documented new onset of positive lower respiratory tract culture (e.g., throat swab, sputum, or BAL) for PA within 30 days of study entry (prior to screening visit) defined as either first lifetime documented PA-positive culture OR PA recovered after at least a 2 year history of PA-negative respiratory cultures (at least 2 cultures per year)
- •Forced expiratory volume in 1 second (FEV1) ≥ 80% predicted at screening visit (subjects ≥ 6 years of age)
- •Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would have required administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.
- •All sexually active females who were of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study. Females utilizing hormonal contraceptives as a birth control method must have used the same method for at least 3 months prior to study drug dosing.
- •Males must agree to use barrier contraception (condom with spermicide) during heterosexual intercourse from screening through to study completion and for 90 days from the last dose of study investigational medicinal product
- •Participants and/or parent/guardian must be able to give written informed consent prior to any study related procedure
排除标准
- •Use of IV or inhaled antipseudomonal antibiotics within 2 years of study entry (screening visit)
- •Use of oral antipseudomonal antibiotics within 30 days of study entry (screening visit)
- •History of sputum or throat swab culture yielding Burkholderia spp. within 2 years prior to screening visit
- •History of local or systemic hypersensitivity to monobactam antibiotics
- •History of intolerance to inhaled short acting beta 2 agonists
- •History of lung transplantation
- •History of AZLI (or Cayston®) administration
- •Administration of any investigational drug or device within 28 days prior to screening visit or within 6 half-lives of the investigational drug (whichever is longer)
- •Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone per day or 20 mg prednisone every other day
- •Current requirement for daily continuous oxygen supplementation or requirement of more than 2 L/minute at night
- •Hospitalization for pulmonary-related illness within 28 days prior to screening visit
- •Changes in or initiation of chronic azithromycin treatment within 28 days prior to screening visit
- •Changes in antimicrobial, bronchodilator (BD), corticosteroid, dornase alfa, or hypertonic saline medications within 7 days prior to screening visit; for participants on a stable regimen of hypertonic saline (28 days on/28 days off), beginning or ending a cycle of hypertonic saline is allowed
- •Changes in physiotherapy technique or schedule within 7 days prior to screening visit
- •Abnormal renal or hepatic function results at most recent test within the previous 12 months, defined as:
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit of normal (ULN), or
- •Serum creatinine > 2 times ULN for age
- •Pregnant or lactating females; a negative urine pregnancy test is required for all females of childbearing potential (unless surgically sterile), and confirmatory serum pregnancy test in the event of an initial positive urine test result
- •Any serious or active medical or psychiatric illness (including drug or alcohol abuse), which in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol
- •Presence of a condition or abnormality that would compromise the patient's safety or the quality of study data, in the opinion of the investigator
研究组 & 干预措施
Aztreonam for Inhalation Solution (AZLI)
Participants will receive one 28-day course of AZLI, then will be followed for a 24-week period (through Day 196).
干预措施: Aztreonam for Inhalation Solution (AZLI) (Drug)
结局指标
主要结局
Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Evaluable Analysis Set)
时间窗: Day 28 to Day 196
The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Evaluable Analysis Set.
Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Sensitivity Analysis Set)
时间窗: Day 28 to Day 196
The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Sensitivity Analysis Set.
次要结局
- Change From Baseline in FEV1% Predicted(Baseline to Days 28, 56, 112, and 196)
- Use of Additional (Non-study) Antipseudomonal Antibiotics(Baseline to Day 196)
- Change From Baseline in CFQ-R RSS Score(Baseline to Days 28, 56, 112, and 196)
- Percentage of Participants With PA-negative Cultures(Days 28, 56, 112, and 196)
- Change From Baseline in Weight(Baseline to Days 28, 56, 112, and 196)
- Change From Baseline in Height(Baseline to Days 28, 56, 112, and 196)
- Change From Baseline in Body Mass Index (BMI)(Baseline to Days 28, 56, 112, and 196)
- Pharmacokinetics (PK) Peak and Trough Plasma Concentrations of Aztreonam(Day 1 (1 hour postdose) and Day 28 (immediately prior to dosing))