A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Food Effects of Single and Multiple Ascending Doses of QLS12010 Capsules in Healthy Adult Participants and Participants With Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment emergent Adverse Events as assessed by CTCAE v5.0
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety, tolerability, PK, and PD of single and multiple ascending doses of QLS12010 Capsules and the effect of food on their PK profiles in healthy adult participants and participants with atopic dermatitis. This study consists of four parts: Part A is a single ascending dose (SAD) study, once sufficient safety and PK data are obtained from the SAD cohorts, the SMC will determine the dosage of initial cohort in Part B, which consists of three multiple ascending doses (MAD) cohorts of QLS12010 Capsules. Part C is a randomized, open-label, two-cycle, crossover food effect study under fasting and fed (high-fat meal) conditions. Part D is to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and preliminary efficacy of QLS12010 Capsules following multiple oral administrations in adult participants with atopic dermatitis (AD).
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Participants with diseases that should be excluded as judged by the investigator at screening, including but not limited to the nervous system, psychiatric system, cardiovascular system, blood and lymphatic system, immune system, respiratory system, digestive system, urinary system, metabolic and skeletal system disorders,
- •The 12-lead ECG at screening shows QTcF (QT corrected using Fridericia's formula) > 450 ms. If QTcF is > 450 ms, the 12-lead ECG should be repeated 2 more times (at least 3 min apart), and the mean of the 3 measurements will be used to determine whether the participant meets the inclusion criteria,
- •Participants who smoke more than 5 cigarettes per day on average within 6 months before screening or are currently using e-cigarettes,
- •Participants who consume more than 14 units of alcohol per week (1 unit = 360 mL of beer, 45 mL of 40% spirits, or 150 mL of wine) within 6 months before screening or have a positive breath alcohol test at screening,
- •Participants who have donated more than 400 mL of blood within 3 months or more than 200 mL of blood within 4 weeks before screening, or plan to donate blood during the study,
- •Participants who have received any strong inhibitor or inducer of CYP3A4 within 4 weeks before screening,
- •Participants who have received any prescription drugs, OTC drugs, traditional medicines, and dietary supplements within 2 weeks before the first dose or 5 half-lives (whichever is longer).
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Single ascending dose cohorts in healthy participants
Healthy volunteer subject cohorts randomized 6:2 receiving a single dose of QLS12010 or placebo. The starting dose will be 25 mg of QLS12010 or placebo.
干预措施: QLS12010 (Drug)
Single ascending dose cohorts in healthy participants
Healthy volunteer subject cohorts randomized 6:2 receiving a single dose of QLS12010 or placebo. The starting dose will be 25 mg of QLS12010 or placebo.
干预措施: Placebo (Drug)
Multiple ascending dose cohorts in healthy subjects
Healthy volunteer subject cohorts randomized 8:2 to receive QLS12010 or placebo QD for 14 continuous days. The starting dose of QLS12010 or placebo is based on upcoming data from SAD part.
干预措施: QLS12010 (Drug)
Multiple ascending dose cohorts in healthy subjects
Healthy volunteer subject cohorts randomized 8:2 to receive QLS12010 or placebo QD for 14 continuous days. The starting dose of QLS12010 or placebo is based on upcoming data from SAD part.
干预措施: Placebo (Drug)
Food Effect Cohort in healthy subjects
Part C is a two-cycle, crossover study under fasting and fed (high-fat meal) conditions. In Cycle 1, 12 healthy adult participants will be randomly divided into two groups on D-1, with 6 participants in each group receiving a single oral dose of QLS12010 Capsules under fasting or fed conditions, respectively. After completing washout, they will receive crossover administration for the Cycle 2 study.
干预措施: QLS12010 (Drug)
Early Efficacy in patients with AD
Part D of the study plans to enroll 12 adults with moderate to severe atopic dermatitis (AD). Eligible subjects (after screening) will be sequentially assigned to two dose groups (Dose 1 and Dose 2) in the order of their enrollment. Enrollment of Dose 2 may commence only after Dose 1 has completed enrollment of 6 subjects.
干预措施: QLS12010 (Drug)
结局指标
主要结局
Incidence and severity of treatment emergent Adverse Events as assessed by CTCAE v5.0
时间窗: up to approximately 1 month
次要结局
- Area under the curve plasma concentration from time zero to last measurable concentration [AUC(0-last)](up to approximately 1 month)
- Area under the curve plasma concentration from time zero to infinity [AUC(0-∞)](up to approximately 14 days)
- Maximum observed plasma concentration (Cmax)(up to approximately 1 month)
- Time to maximum observed plasma concentration (Tmax)(up to approximately 1 month)
- Terminal elimination half-life (t1/2)(up to approximately 1 month)
- Apparent clearance (CL/F)(up to approximately 1 month)
- Apparent volume of distribution (Vz/F)(up to approximately 1 month)
- Mean residence time (MRT)(up to approximately 1 month)
- Changes and percentage changes from baseline in Eczema Area and Severity Index (EASI) scores(at Weeks 1, 2, 3, 4, 5, and 6)
- Changes and percentage changes from baseline in Investigator's Global Assessment (IGA) scale(at Weeks 1, 2, 3, 4, 5, and 6)
- Changes and percentage changes from baseline in weekly mean scores of Peak Pruritus Numerical Rating Scale (PP NRS)(at Weeks 1, 2, 3, 4, 5, and 6)
- Changes and percentage changes from baseline of body surface area (BSA) affected by lesions(at Weeks 1, 2, 3, 4, 5, and 6)