A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PUL-042 Inhalation Solution in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicities (DLTs)
研究概览
简要总结
The purpose is to determine if single doses of PUL-042 inhalation solution are safe in healthy subjects.
详细描述
The study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of PUL-042 inhalation solutions in healthy subjects.
Subjects will be enter a screening period of up to 14 days to determine eligibility. Subjects will be admitted to the Phase 1 unit the day prior to dosing and remain in the unit until 24 hours post-dose. Subjects will be seen in the clinic at 3 and 7 days post-dose
A modified 3+3 design will be used to determine the maximum tolerated dose (MTD) based on the occurrence of dose-limiting toxicities (DLTs) defined by Common Terminology Criteria for Adverse Events (CTCAE) v4. Additional specific DLTs will be defined as: 1) Hypoxia, defined as a non-artifactual drop in pulse oximetry to < 90% on room air, 2) A decrease in forced expiratory volume in one second (FEV1) of 12% or greater compared to the last observation prior to dosing, 3) Any evidence of bronchospasm or wheezing requiring medical intervention. Doses will be doubled until the maximum tolerated dose (MTD- defined as the largest dose with 0/6 or 1/6 DLTs) is reached.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males or females of non-childbearing potential
- •Body mass index between 18 and 30 kg/m2
- •Normal spirometry
- •Normal diffusing capacity of lung for carbon monoxide
- •Normal pulse oximetry
- •Males willing to practice contraception or have a female partner using contraception
排除标准
- •Abnormal chest x-ray
- •History of tobacco products within the last year and total exposure of > 5 pack/years
- •Clinically significant laboratory findings
- •History of chronic pulmonary disease
- •History of atopic reactions
- •Mediastinal lymphadenopathy
- •Oral corticosteroid therapy within 4 weeks prior to randomization
- •Alcohol, caffeine or strenuous exercise within 72 hours prior to dosing
- •Grapefruit within 7 days prior to dosing
- •Administration of concomitant medications within 14 days prior to dosing
- •Exposure to any investigational agent with 30 days
- •Significant concurrent illness
- •Know positive for HIV, hepatitis B or hepatitis C
- •Inability to tolerate a nebulization test with sterile water for injection
- •Positive test for drugs of abuse
研究组 & 干预措施
PUL-042 Inhalation Solution
Fixed dose combination of Pam2CSK4 acetate (Pam2) and ODN M362 (ODN) administered as an inhalation solution. Single dose administration by nebulization. Starting dose will be 2.9 micrograms Pam2: 4.25 micrograms ODN. Up to 7 doubling doses may be tested.
干预措施: PUL-042 Inhalation Solution (Drug)
Sterile water for injection
Sterile water for injection administered by nebulization
干预措施: PUL-042 Inhalation Solution (Drug)
结局指标
主要结局
Dose-limiting toxicities (DLTs)
时间窗: Dosing to one week post-dose
次要结局
未报告次要终点