Phase 1b/2a Multidose Safety and Tolerability Study of Liposomal Amikacin for Inhalation (Arikayce™) in Cystic Fibrosis Patient With Chronic Infections Due to Pseudomonas Aeruginosa.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events
研究概览
简要总结
This is a study to determine the safety and tolerability of 28 days of daily dosing of 560 mg of Arikayce™ versus placebo and daily dosing of 70 mg and 140 mg of Arikayce™ versus placebo in patients who have Cystic fibrosis (CF) and chronic infection due to pseudomonas aeruginosa.
详细描述
CF is a gentic disease resulting from mutations in a 230 kb gene on chromosome 7 known as the cystic fibrosis transmembrane conductance regulator (CFTR). Study subjects with CF manifest pathological changes in a variety or organs that express CFTR. The lungs are frequently affected, the sequelae being chronic infections and airway inflammation. The principal goal of both treatment of subjects with CF is to slow the chronic deterioration of lung function.
Study subjects will be randomized to receive either study drug or placebo (1.5% NaCl) by inhalation via a PARI eFlow nebulizer. Each subject will complete 28 days of daily dosing. All study patients will be followed for safety, pharmacokinetics, clinical and microbiologic activity for 56 days post completion of study treatment. For the two lower doses (70 mg and 140 mg): patients received drug for 28 days, followed by a 28 day safety evaluation. For 560 mg: patients received drug for 28 days, followed by a 56 day safety evaluation. The total study period will be up to 84 days, with screening visit occurring within the preceding 14 days prior to study day 1. Patients will be clinically evaluated during the first 48 hours post first study dose and weekly for the 28 day treatment period and during the follow up visits at study days 35, 42, 49, 56, 70 and 85 days to determine safety and tolerability, pharmacokinetics (PK) and clinical and microbiologic activity.
Clinical laboratory parameters, audiology testing, clinical adverse events and pulmonary function will be evaluated for all study subjects in order to determine the qualitative and quantitative safety and tolerability of Arikayce™ compared to placebo. Serum, urine and sputum specimens will be collected at periodic intervals to assess PK. Additionally, sputum samples will be collected to determine changes in bacterial density. Pulmonary function testing and CFQ-R measurements will be assessed at selected time points throughout the study. An exploratory evaluation of a Cystic Fibrosis Symptom Diary (CFSD) will also be implemented. Arikace™,Arikayce™, Liposomal Amikacin for Inhalation (LAI), and Amikacin Liposome Inhalation Suspension (ALIS) may be used interchangeably throughout this study and other studies evaluating amikacin liposomal inhalation suspension.
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
- •Male or female study subjects must be adults (≥ 6 years of age)
- •Confirmed diagnosis of CF
- •History of chronic infection with P.aeruginosa
- •FEV1 ≥40% of predicted at Screening
- •Ability to comply with study medication use, study visits and procedures
- •Ability to produce 0.5 grams of sputum
排除标准
- •Administration of any investigational drug within 8 weeks to Study Day 1
- •Emergency room visit or hospitalization for CF or respiratory-related illness within 4 weeks prior to screening
- •History of alcohol, medication or illicit drug abuse within 1 yr. to screening
- •History of lung transplantation
- •Female of childbearing potential who are not practicing an acceptable method of birth control or who are lactating
- •Positive Pregnancy test
- •Use of any anti-pseudomonal antibiotics within 28 days prior to Study Day 1
- •Initiation of chronic therapy within 28 days prior to Study Day 1
- •History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years prior to screening
- •History of mycobacterial and/or Aspergillus infection requiring treatment within 2 years prior to screening
- •History of biliary cirrhosis with portal hypertension, or splenomegaly
研究组 & 干预措施
A
Arikayce™ at 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.
干预措施: Arikayce™ 560 mg (Drug)
B
Matching placebo for 560 mg Subjects randomized 2:1 to receive Arikayce 560 mg or Placebo.
干预措施: Placebo for 560 mg (Drug)
C
Arikayce™ at 70 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
干预措施: Arikayce™ 70 mg (Drug)
D
Arikayce™ at 140 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
干预措施: Arikayce™ 140 mg (Drug)
E
Matching placebo for 70 mg/140 mg Subjects randomized 1:1:1 to receive Arikayce 70 mg, Arikayce 140 mg or Placebo.
干预措施: Placebo for 70 mg / 140 mg (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events
时间窗: 56 days
To evaluate the safety and tolerability of 28 days of daily dosing of nebulized Arikayce™, liposomal amikacin for inhalation.
次要结局
- Pharmacokinetics of Arikayce™ in Serum(Day 1, Day 14 and Day 28)
- Pharmacokinetics (PK) of Arikayce™ in Sputum(Day 1 post-dose, Day 14 pre- and post-dose, Day 28 pre- and post-dose)
- Duration of Systemic Anti-Pseudomonal Rescue Therapy(Through study duration, approximately 84 days)
- Pharmacokinetics (PK) of Arikayce™ in Urine(Day 1, Day 14 and Day 28)
- Pharmacokinetics (PK) of Arikayce™ in Serum(Day 1, Day 14 and Day 28)
- Pulmonary Function: Pre-Dose FEV1 (%-Predicted)(Baseline, Day 28, Day 56, Day 70 and Day 84)
- Density of Pseudomonas Aeruginosa in Sputum(Day 7, Day 14, Day 21, Day 28 and Day 35)
- CFQ-R Respiratory Scale (Relative Change % From Baseline)(Day 15, Day 28 and Day 42)