A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Single and Multiple Doses of KH607 Tablets in Chinese Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Stanford Sleepiness Scale
研究概览
简要总结
This study was a single-center, randomized, double-blind, placebo-controlled study divided into a Single Ascending Dose (SAD) stage and a Multiple Ascending Dose (MAD) stage. The primary objective was to evaluate the safety and tolerability of KH607 tablets in Chinese healthy volunteers.
详细描述
This study consists of two parts: Part 1-SAD phase and Part 2- MAD phase. There will be eight cohorts in Part 1 and three cohorts in Part 2 of this study.
The SAD study will enroll approximately 58 HVs across 8 dose cohorts. The dose cohorts will include the following dose levels: 2 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, 50mg and 60 mg. All participants in Part 1 will be administered with a single oral dose of KH607 or its matching placebo under fasted condition.
Approximately 30 HVs will be enrolled in the multiple ascending dose study. The dose cohorts will include the following dose levels: 10 mg, 20 mg, 30 mg.At each cohort, 10 subjects will be randomized in a ratio of 8:2 to be receive KH607 or placebo once daily for continuous 7 days (QDx7d) in a double-blind manner.
Additionally, this study will explore the effect of food on the PK of a single oral administration of KH607 in one selected SAD cohort.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult, male and female volunteers, 18 to 55 years of age, inclusive.
- •Male weight ≥ 50kg, female weight ≥ 45kg, and body mass index ≥ 19 to ≤ 28 kg/m2 at the screening period.
排除标准
- •Vulnerable groups include the Investigator and his or her immediate family members (spouse, parents, children, siblings), non-immediate family members involved in the study, or individuals who may be participating under coercion or undue influence.
- •Subjects whose C-SSRS suggests that they are at risk for suicide at the screening period, or with the risk for suicide based on the Investigator's clinical judgment, or with a history of suicidal or self-harming behavior.
- •Subjects with SSS ≥3 or MOAA/S ≤4 during the screening period.
- •Subjects with a history of surgery for gastrointestinal disorders or current GI disorders that may interfere with drug absorption, or who have undergone major surgery within the 3 months prior to the screening period.
研究组 & 干预措施
KH607 Cohort 1
Subject received a single KH607 tablets dose of 2mg KH607 tablets or matching placebo.
干预措施: 2mg KH607 tablets (Drug)
KH607 Cohort 2
Subject received a single KH607 tablets dose of 5mg KH607 tablets or matching placebo.
干预措施: 5mg KH607 tablets (Drug)
KH607 Cohort 3
Subject received a single KH607 tablets dose of 10mg KH607 tablets or matching placebo.
干预措施: 10mg KH607 tablets (Drug)
KH607 Cohort 4
Subject received a single KH607 tablets dose of 20mg KH607 tablets or matching placebo.
干预措施: 20mg KH607 tablets (Drug)
KH607 Cohort 5
Subject received a single KH607 tablets dose of 30mg KH607 tablets or matching placebo.
干预措施: 30mg KH607 tablets (Drug)
KH607 Cohort 6
Subject received a single KH607 tablets dose of 40mg KH607 tablets or matching placebo.
干预措施: 40mg KH607 tablets (Drug)
KH607 Cohort 7
Subject received a single KH607 tablets dose of 50mg KH607 tablets or matching placebo.
干预措施: 50mg KH607 tablets (Drug)
KH607 Cohort 8
Subject received a single KH607 tablets dose of 60mg KH607 tablets or matching placebo.
干预措施: 60mg KH607 tablets (Drug)
KH607 Cohort 9
Subject received 10mg KH607 or matching placebo, oncely daily from Day 1 to Day 7.
干预措施: 10mg KH607 tablets (Drug)
KH607 Cohort 10
Subjects receive 20mg KH607 or matching placebo, once daily from Day 1 to Day 7.
干预措施: 20mg KH607 tablets (Drug)
KH607 Cohort 11
Subjects receive 30mg KH607 or matching placebo, once daily from Day 1 to Day 7.
干预措施: 30mg KH607 tablets (Drug)
结局指标
主要结局
Stanford Sleepiness Scale
时间窗: Screening up to Part 1 Day3，Part 2 Day14.
Participants rate their current sleepiness on a scale of 1 to 7, where scale of 1 indicates feeling active, vital, alert, or wide awake. Scale of 7 indicates no longer fighting sleep, sleep onset soon, and having dream-like thoughts.
12-lead ECGs
时间窗: Screening up to Part 2 Day14.
Using a standard 12-lead ECG machine that automatically calculate heart rate and measures PR interval, RR interval, QRS interval, QT interval, QTc interval. ECGs will be reviewed by the Investigator on an ongoing basis as safety assessments.
Modified Observer's Assessment of Alertness/Sedation scale
时间窗: Screening up to Part 1 Day3，Part 2 Day14.
The MOAA/S ranges from 0 to 5, with a score of 5 defined as awake or minimally sedated, and a score of 0 defined as general anaesthesia.
Physical Examination
时间窗: Screening up to Part 1 Days, Part 2 Day14.
次要结局
- Apparent Distribution Volume (Vd)(Up to 48 hours after dosing in Part 1.)
- Elimination Rate Constant (Kel)(Up to 48 hours after dosing in Part 1.)
- Apparent Total Plasma Clearance (CL)(Up to 48 hours after dosing in Part 1.)
- Observed maximum plasma concentration (Cmax)(Up to 48 hours after dosing in Part 1.)
- Steady-state valley concentration（Css,min）(Up to 24 hours after Day7 dosing in Part 2.)
- Mean Residence Time(MRT)(Up to 48 hours after dosing in Part 1.)
- Columbia-Suicide Severity Rating Scale(Screening up to Part 1 Day3，Part 2 Day14.)
- Elimination Halflife (T1/2)(Up to 48 hours after dosing in Part 1.)
- Time to reach maximum plasma concentration (Tmax)(Up to 48 hours after dosing in Part 1.)
- Area under the concentration-time curve from time zero to last time of quantifiable concentration（AUC0-t）(Up to 48 hours after dosing in Part 1.)
- Steady-state peak concentration（Css,max）(Up to 24 hours after Day7 dosing in Part 2.)
- Mean steady-state blood concentration（Css,av）(Up to 24 hours after Day7 dosing in Part 2.)
- Steady state area under the curve（AUC0-tau）(Up to 24 hours after Day7 dosing in Part 2.)
- Accumulation Index（Rac）(Up to 24 hours after Day7 dosing in Part 2.)