A Single-Center, Open-label, Randomized, Single Dose, Two-way Crossover Design to Evaluate the Relative Bioavailability of Two Different Pimicotinib Capsules Under Fasting Conditions in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Cmax
研究概览
简要总结
This is a study to evaluate the relative bioavailability and tolerability of two different pimicotinib capsules in healthy subjects under fasting condition. 26 healthy subjects are planned to be enrolled and will be evenly randomized to either Study Sequence A or Study Sequence B . Subjects in Sequence A/Sequence B will receive a single 50 mg oral dose of test/reference pimicotinib in period 1 and cross over in period 2. Blood samples will be collected for PK analysis in totally 32 time-points.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects aged 18 to 50 years (inclusive) at screening;
- •Weight ≥ 50.0 kg (male) or ≥ 45.0 kg (female);
- •Normal or abnormal but not clinically significant results in medical history, physical examination, clinical laboratory tests and other relevant examinations as assessed by the investigator at Screening;
- •Male or female subjects of childbearing potential must agree to use effective methods of contraception during the study and within 6 months after the last dose of investigational product;
- •Willing to participate in this study, understand the study procedures and sign the informed consent form prior to screening; willing to comply with the study procedures.
排除标准
- •Past or current medical history of chronic or severe conditions in cardiovascular, respiratory, blood, liver, kidney, gastrointestinal, endocrine or nervous systems;
- •Known or persistent mental disorders;
- •Past history of gastric or intestinal surgery, or other operations;
- •Dysphagia and inability to take the investigational product orally;
- •Intolerant to venipuncture, difficult to collect blood samples, and fear of needle sickness and blood;
- •Known allergy to two or more kinds of foods and drugs; or allergic to pimicotinib or its excipients;
- •History of infection within 30 days prior to screening;
- •Symptoms of fatigue and pyrexia within 2 weeks prior to screening;
- •Abnormal laboratory tests;
- •Positive result for either of the following tests: serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) antibody, Human Immunodeficiency Virus (HIV) antibody, and treponema pallidum antibody;
- •Participated in any clinical studies of drugs as a study subject and received the study drug within 3 months prior to screening;
- •Previously participated in any other study related to pimicotinib and received pimicotinib;
- •Used strong inhibitors or inducers of CYP3A4 within 14 days prior to screening and at Screening or intending to use during the study;
- •Have special diet requirements and cannot accept to take a unified dietary;
- •Consumption of more than 14 units of alcohol per week within 3 months prior to signing the informed consent form, or a positive result for alcohol breath test on the day pre-dose, or unable to abstain from alcohol during the study;
- •Consumption of more than 5 cigarettes per day within 3 months prior to signing the informed consent form, or unable to abstain from tobacco products during the study;
- •Previous chronic consumption of excessive amount of tea, coffee, or caffeinated beverages or unable to abstain from caffeinated beverages during the study;
- •Known history of drug abuse or positive for drug abuse screening test;
- •Used over the counter or prescription drugs within 14 days prior to screening, or plan to use such drugs during the study;
- •Donated or lost > 400 mL of blood within 3 months prior to screening; received blood transfusions or used blood products within 2 months prior to screening;
- •Received vaccine within 2 months prior to screening, or plan to get vaccinated during the study;
- •Significant abnormalities and judged by the investigator as clinical significance in vital signs;
- •Heart rate-corrected QT interval prolongation;
- •Subjects involved in the design or conduct of this study and their immediate family members;
- •Subjects who, in the opinion of the investigator, are not suitable for enrollment or may not be able to complete the study for other reasons.
研究组 & 干预措施
pimicotinib (test capsule-reference capsule)
subjects in sequence A will receive a single oral dose of 50 mg test capsule administered as 2 x 25 mg (the capsule is commercial formulation to be marketed) in period 1 day 1 and receive a single oral dose of 50 mg reference capsule administered as 2 x 25 mg (the capsule was used in phase 3 study Part 1) in period 2 day 1.
干预措施: pimicotinib capsules (Drug)
pimicotinib (reference capsule-test capsule)
subjects in sequence B will receive a single oral dose of 50 mg reference capsule administered as 2 x 25 mg (the capsule was used in phase 3 study Part 1) in period 1 day 1 and receive a single oral dose of 50 mg test capsule administered as 2 x 25 mg (the capsule is commercial formulation to be marketed) in period 2 day 1 .
干预措施: pimicotinib capsules (Drug)
结局指标
主要结局
Cmax
时间窗: Period 1& Period 2: pre-dose, postdose 15 minutes, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours, 96 hours, 120 hours, 144 hours, 192 hours and 240 hours.
Peak concentration, the maximum observed plasma concentration of pimicotinib
AUC0-∞
时间窗: Period 1& Period 2: pre-dose, postdose 15 minutes, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours, 96 hours, 120 hours, 144 hours, 192 hours and 240 hours.
Area under the plasma concentration-time curve of pimicotinib from time 0 to infinity, calculated as: AUC0-∞=AUClast +Clast/λz; Clast refers to the last measurable (non-BQL) plasma concentration of pimicotinib.
AUClast
时间窗: Period 1& Period 2: pre-dose, postdose 15 minutes, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours, 96 hours, 120 hours, 144 hours, 192 hours and 240 hours.
Area under the plasma concentration-time curve of pimicotinib from time 0 to the time of last measurable (non-BQL) concentration (calculated using the Linear Up Log Down trapezoidal method)
次要结局
- AE(through study completion, an average of 24 days)
- t1/2(Period 1& Period 2: pre-dose, postdose 15 minutes, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours, 96 hours, 120 hours, 144 hours, 192 hours and 240 hours.)
- CL/F(Period 1& Period 2: pre-dose, postdose 15 minutes, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours, 96 hours, 120 hours, 144 hours, 192 hours and 240 hours.)
- Vz/F(Period 1& Period 2: pre-dose, postdose 15 minutes, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours, 96 hours, 120 hours, 144 hours, 192 hours and 240 hours.)