A Phase 1 Open-label, Cross-over Study to Assess the Effects of Food on PC14586 Pharmacokinetics in Healthy Volunteers and to Assess PC14586 Pharmacokinetics in Healthy Japanese Volunteers Living in the US
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Part 2: Effect of a high-fat meal on the Cmax
研究概览
简要总结
This is a 2-part Phase 1 cross-over study to assess the effects of food on the pharmacokinetics of PC14586 in healthy volunteers. The pharmacokinetics of PC14586 at a clinically relevant dose in Japanese participants will also be studied.
详细描述
PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the p53 Y220C mutation. This Phase 1 trial will be conducted in 2 parts (Part 1 - pilot and Part 2 - pivotal) to assess the pharmacokinetics of PC14586 in healthy volunteers including Japanese participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
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
- •Healthy, non-smoking male and female Caucasian/ non-Asian or Japanese human volunteers
- •18 to 55 years of age
- •Able to swallow tablets.
- •Inclusion criteria for Japanese participants only:
- •Japanese and born in Japan (1st generation)
- •The parents and grandparents of the participant are ethnically Japanese and born in Japan
- •Has undergone no significant change in lifestyle since leaving Japan
- •Has lived < 10 years outside of Japan
排除标准
- •Clinically significant medical history as determined by the PI.
- •Any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs.
- •A p53 Y220C mutation.
- •Blood pressure >140 mm systolic or >90 diastolic.
- •Smoked or used other nicotine-containing products during the previous 3 months.
- •History of alcohol and/or illicit drug abuse within the previous 5 years.
- •Hepatitis B surface antigen (HBsAg), Hepatitis C antibody or human immunodeficiency virus (HIV).
- •Positive blood test for ethanol.
- •Positive urine drug test.
- •Pregnancy or breastfeeding.
- •Unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to admission until discharge from the clinical site.
- •Has donated blood within 2 months prior to admission.
- •Has used over-the-counter (OTC) medications (including vitamins), prescription medications or herbal remedies from 14 days prior to admission.
- •Has used an investigational drug within 30 days prior to Screening.
研究组 & 干预措施
Part 1 Sequence A
Period 1 will be fed, then washout, then Period 2 will be fasted.
干预措施: PC14586 (Drug)
Part 1 Sequence B
Period 1 will be fasted, then washout, then Period 2 will be fed.
干预措施: PC14586 (Drug)
Part 2 Sequence C
Period 1 will be fed, then washout, then Period 2 will be fasted. A different dose of PC14586 will be tested.
干预措施: PC14586 (Drug)
Part 2 Sequence D
Period 1 will be fasted, then washout, then Period 2 will be fed. A different dose of PC14586 will be tested.
干预措施: PC14586 (Drug)
Part 2 Japanese Cohort
6 Japanese participants will be administered a single dose of PC14586.
干预措施: PC14586 (Drug)
结局指标
主要结局
Part 2: Effect of a high-fat meal on the Cmax
时间窗: 7 months
Part 1: Effect of a high-fat meal on the Cmax
时间窗: 2 months
Part 2: Effect of a high-fat meal on the AUC0-inf
时间窗: 7 months
Part 1: Effect of a high-fat meal on the Tmax
时间窗: 2 months
Part 1: Effect of a high-fat meal on AUClast
时间窗: 2 months
Part 1: Effect of a high-fat meal on AUC0-inf
时间窗: 2 months
Part 2: Effect of a high-fat meal on the AUC0-last
时间窗: 7 months
Part 2: Effect of a high-fat meal on the Tmax
时间窗: 7 months
次要结局
- Part 2: AUC0-inf of PC14586(6 months)
- Part 2: Cmax of PC14586(6 months)
- Part 2: Volume of distribution (Vz/F) of PC14586(6 months)
- Half-life of PC14586(6 months)
- Part 2: Incidence of Treatment emergent adverse events (TEAE)(10 months)
- Part 2: The apparent clearance (CL/F) of PC14586(6 months)
- Part 1: Treatment emergent adverse events (TEAE)(5 months)
- Part 1: Clinically relevant changes in: physical examinations, vital signs, clinical laboratory tests, 12-lead triplicate electrocardiogram (ECG)(5 months)
- Part 2: AUC0-last of PC14586(6 months)
- Part 2: Tmax of PC14586(6 months)