A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Assess Safety, Tolerability, and Pharmacokinetics of AN01 Inhalation Powder in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Number of participants with abnormal clinically significant respiratory assessment findings following study drug administration
研究概览
简要总结
AN01 is a selective small-molecule dual inhibitor of phosphodiesterase 3 and 4 (PDE3/4).
As a potential new therapy for COPD, AN01 is expected to serve either as a monotherapy for COPD or as adjunctive therapy to current inhaled standard treatments, potentially generating synergistic complementary effects in patients requiring additional therapeutic options.
The primary objective of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of AN01 in healthy participants.
详细描述
The study is composed of three multiple ascending dose (MAD) cohorts in which participants will be randomly allocated to receive placebo or ascending doses of active AN01 in a double-blinded manner. An additional multiple ascending dose cohort may be added at Sponsor's discretion.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults ≥18 and ≤60 years (inclusive).
- •Body Mass Index (BMI) ≥18 and ≤32 kg/m2 (inclusive).
- •Participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, spirometry, and electrocardiogram (ECG).
- •Non-smokers or former smokers who have quit for ≥2 years with a prior smoking history of <5 pack-years (pack-years defined as = cigarettes per day × years smoked; 1 pack = 20 cigarettes).
- •Female participants must be non-pregnant and non-lactating, and, surgically sterile, use highly effective contraceptive methods from Screening until at least 30 days after the last dose of study drug, or post-menopausal for ≥12 months.
- •Male participants must be surgically sterile, abstinent, or their partner must be surgically sterile, or if engaged in sexual relations with a woman of childbearing potential (WOCBP), the male participant and his partner must use an acceptable, highly effective contraceptive method from Screening until at least 90 days after the last dose of study drug.
排除标准
- •History of clinically significant (as per Investigator's judgment) upper respiratory disease or history of any significant pulmonary disease including, but not limited to, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and history of previous tuberculosis exposure with positive interferon gold test (without actual infection).
- •Participants with any history of, or active, clinically significant disease (e.g., cardiovascular disease, chronic liver disease, psychiatric medical history, renal disease) that could interfere with the interpretation of the study results or compromise the health of the participant based on the judgment of the Investigator.
- •Administration of vaccines/immunizations and/or boosters within 8 days prior to first dosing or if planned during the study.
- •Any history of active infection at the time of Screening and/or within 28 days prior to first dosing.
- •Any prior participation in a study with an investigational drug or device involving a biological targeted therapy, where final administration of the investigational drug or utilization of the device occurred within 24 weeks prior to first dosing.
- •History of migraine headaches requiring prescription medication or occurring more than 2-4 times per month within the past 6 months.
- •Use of non-tobacco vaping within 12 months prior to Screening.
- •Use of any tobacco and/or inhaled marijuana product within 2 years prior to Screening.
研究组 & 干预措施
Placebo
Escalating doses of matching placebo
干预措施: Placebo (Drug)
AN01
Escalating multiple doses of AN01
干预措施: AN01 (Drug)
结局指标
主要结局
Number of participants with abnormal clinically significant respiratory assessment findings following study drug administration
时间窗: Day 1 - Day 6
Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters following study drug administration
时间窗: Day 1 - Day 14
Incidence, severity, relationship to the investigational drug, and types of adverse events and serious adverse events
时间窗: Day 1 - Day 14
Number of participants with abnormal clinically significant physical examination (PE) results following study drug administration
时间窗: Day 1 - Day 14
Number of participants with abnormal clinically significant vital signs following study drug administration
时间窗: Day 1 - Day 14
Number of participants with abnormal clinically significant clinical laboratory results following study drug administration
时间窗: Day 1 - Day 14
Number of participants with abnormal clinically significant spirometry parameters following study drug administration
时间窗: Day 1 - Day 6
次要结局
- PK parameter assessed by serum AN01 concentration at specified timepoints for area under curve (AUC)(Day 1 - Day 9)
- PK parameter assessed by serum AN01 concentration at specified timepoints for maximum plasma concentration (Cmax)(Day 1 - Day 9)
- PK parameter assessed by serum AN01 concentration at specified timepoints for time to peak concentration (Tmax)(Day 1 - Day 9)
- PK parameter assessed by serum AN01 concentration at specified timepoints for terminal elimination half life (t1/2)(Day 1 - Day 9)
- PK parameter assessed by serum AN01 concentration at specified timepoints for apparent clearance volume (CL/F)(Day 1 - Day 9)
- PK parameter assessed by serum AN01 concentration at specified timepoints for apparent volume of distribution (Vd/F)(Day 1 - Day 9)
- PK parameter assessed by serum AN01 concentration at specified timepoints for terminal elimination rate constant (λz)(Day 1 - Day 9)