A Phase IIa Open Label Study to Evaluate the Safety, Tolerability and Efficacy of S-1226 Administered by Nebulization in Subjects With Mild to Moderate Cystic Fibrosis and Non CF Bronchiectasis
试验速览
- 阶段
- 2 期
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Treatment-emergent adverse events
研究概览
简要总结
This is a single center, open label, Phase IIa, multiple-ascending dose study in which subjects with mild to moderate Cystic Fibrosis and non CF bronchiectasis (n≤12) will be enrolled.
The safety and tolerability of S-1226 composed of PFOB with ascending doses of carbon dioxide (4%, 8%, and 12% CO2) administered twice daily in subjects with Cystic Fibrosis and non CF bronchiectasis will be evaluated. This will be followed by 5 day consecutive treatment using the highest tolerated dose of S1226. Participants can choose additional use of a further four weeks (28 days) of S-1226 therapy at home, using same or a lower tolerated dose.
详细描述
This is a single center, open label, Phase IIa, multiple-ascending dose study in which subjects with mild to moderate Cystic Fibrosis and non CF bronchiectasis (n≤12) will be enrolled.
The study will consist of a screening period, a run-in and two dosing and evaluation periods (with a minimum two-day break in between) and a follow-up period.
The dosing and evaluation period of the study is divided into two consecutive components:
- Dose escalation study
- This segment of the treatment period is designed to assess the safety and tolerability of escalating doses of S-1226 (4%, 8% and 12%) in those with mild-moderate CF and non CF bronchiectasis
- Daily dosing study - This segment of the treatment period is designed to assess the short term (5 day) safety and tolerability of twice daily administration of a fixed dose of S-1226 in subjects with mild-moderate CF and non CF bronchiectasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose Escalation Study
Subjects will receive up to three inhaled doses of S- 1226. Each dose will be administered over a 2-minute treatment period (with a minimum 2-minute break between treatments) with a nebulizer as follows.
Three S-1226 formulations will be tested sequentially:
- S-1226(4%) is composed of 3 mL PFOB and 4% CO2
- S-1226(8%) is composed of 3 mL PFOB and 8% CO2
- S-1226(12%) is composed of 3 mL PFOB and 12% CO2
Each formulation will be administered by inhalation for a period of 2 minutes.The nebulizer will be filled with 3 mL of PFOB. The nebulizer is connected to a compressed medical gas mixture consisting of either 4%, 8% or 12%, CO2. A driving pressure of 20 psi will be used, producing a gas flow rate of 9 L/min.
干预措施: S-1226 (Drug)
Daily Dosing Study
Eligible subjects will receive S-1226 twice daily for 5 consecutive days. Subjects will receive up to three doses of S-1226 in the morning and afternoon, administered over three 2-minute periods with a Circulaire nebulizer, filled with one of the dosages outlined below, depending on the safety and tolerability data gathered from the dose escalation study for that particular subject.
- S-1226(4%) is composed of 3 mL PFOB and 4% CO2
- S-1226(8%) is composed of 3 mL PFOB and 8% CO2
- S-1226(12%) is composed of 3 mL PFOB and 12% CO2
干预措施: S-1226 (Drug)
结局指标
主要结局
Treatment-emergent adverse events
时间窗: 60 minutes
The number and percent of treatment emergent adverse events will be monitored, recorded and graded for severity and assigned attribution. The severity will be assessed in the following manner: Mild: Awareness of signs or symptoms, but are easily tolerated and are of minor irritant type, causing no limitations of usual activities. Signs or symptoms may require minor action or additional therapy. Moderate: Discomfort severe enough to cause some limitations of usual activities and may require action or additional therapy. Severe: Incapacitating with inability to carry out usual activities and requires specific action and/or medical attention. Note: the term severe is not the same as "serious", which is based on subject/event outcome or action criteria usually associated with events that pose a threat to a subject's life or functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.
次要结局
- Change from baseline in percent of predicted forced expiratory volume in 1 Second(60 minutes)
- Change from baseline in the respiratory domain of Cystic Fibrosis Questionnaire -Revised(Up to 4 weeks)