An Open-Label, Multi-Center, Randomized, 2-Way Crossover Study to Assess the Bioequivalence of APL-101 Capsule vs PLB-1001 Capsule in Healthy Chinese and Caucasian Subjects
试验速览
- 阶段
- 1 期
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration versus time curve (AUC)
研究概览
简要总结
This is a Phase 1, open-label, multi-center, randomized, 2-period, adaptive design, crossover study to assess the bioequivalence of APL-101 (Vebreltinib) capsules and PLB-1001 (Bozitinib) capsules.
The treatments to be administered orally in this study include:
- Treatment A (reference): Two 100 mg APL-101 (Vebreltinib) capsules (200 mg dose), manufactured for Apollomics, Inc
- Treatment P (test): Two 100 mg PLB-1001 (Bozitinib) capsules (200 mg dose), manufactured for Beijing Pearl Biotechnology Co., Ltd.
APL-101 capsules (Treatment A) and PLB-1001 capsules (Treatment P) are similar drug products.
详细描述
Up to 48 healthy male subjects (approximately 16 Chinese and approximately 32 Caucasians) will be enrolled in the study in at least 2 sequential cohorts and randomly assigned to 1 of 2 treatment sequences. The treatment sequence will be determined using a 2×2 crossover design. This study includes an adaptive design feature of variable sample size. Data from the first 16 subjects will be used to determine the intra-subject variability to ensure a sufficient total sample size to achieve study objectives. If needed, up to 72 subjects will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Must be Chinese (1st generation or 2nd generation Chinese with both Chinese parents), or Caucasian.
- •Body mass index between 18.0 and 30.0 kg/m2, inclusive.
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations at screening and at check-in as assessed by the Investigator (or designee). Screening clinical laboratory evaluations may be repeated once at the discretion of the Investigator.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 1.5 × the upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN at screening and check-in. Subjects with ALT or AST >1.0 × ULN combined with total bilirubin >1.0 × ULN are excluded.
- •QT interval corrected for heart rate using Fridericia's method (QTcF) ≤ 450 msec confirmed by calculating the mean of the triplicate measurements within 4 weeks prior to Day
- •Systolic blood pressure between 100 and 140 mmHg or diastolic blood pressure between 50 and 90 mmHg, confirmed by calculating the mean of the triplicate measurements within 4 weeks prior to Day
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator.
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator.
- •Have positive Coronavirus Disease 2019 (COVID-19) test at screening and/or at check-in, have clinical signs or symptoms of COVID-19 as determined by the Investigator, or have ongoing significant complication(s) from prior COVID-19 infection.
- •Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations within 14 days prior to check in, unless deemed acceptable by the Investigator.
- •Have previously completed or withdrawn from this study or any other study investigating APL 101 or similar drug product, and/or have previously received APL 101 or similar drug product.
研究组 & 干预措施
Treatment Sequence A/P
Subject will receive a single oral dose (200mg) of Treatment A on Day 1, followed by a 7-day washout period. On Day 8, the subject will begin the second treatment period by receiving a single oral dose (200 mg) of Treatment P.
干预措施: PLB-1001 (Drug)
Treatment Sequence A/P
Subject will receive a single oral dose (200mg) of Treatment A on Day 1, followed by a 7-day washout period. On Day 8, the subject will begin the second treatment period by receiving a single oral dose (200 mg) of Treatment P.
干预措施: APL-101 (Drug)
Treatment Sequence P/A
Subject will receive a single oral dose (200mg) of Treatment P on Day 1, followed by a 7-day washout period. On Day 8, the subject will begin the second treatment period by receiving a single oral dose (200 mg) of Treatment A.
干预措施: APL-101 (Drug)
Treatment Sequence P/A
Subject will receive a single oral dose (200mg) of Treatment P on Day 1, followed by a 7-day washout period. On Day 8, the subject will begin the second treatment period by receiving a single oral dose (200 mg) of Treatment A.
干预措施: PLB-1001 (Drug)
结局指标
主要结局
Area under the plasma concentration versus time curve (AUC)
时间窗: Day 1 to Day 14
Area under the curve (AUC) from time zero to infinity (AUC0-∞) and from time zero to the last quantifiable concentration (AUC0-last)
Maximum observed plasma concentration
时间窗: Day 1 to Day 14
Maximum observed plasma concentration (Cmax) after dosing of both treatments
次要结局
- Time to the maximum observed plasma concentration(Day 1 to Day 14)
- Number of adverse events observed(Day 1 to Day 20-22)
- Apparent plasma terminal elimination half-life(Day 1 to Day 14)