Bioequivalence
Conditions
Keywords
Pharmacokinetics
Brief summary
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.
Detailed description
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.
Interventions
DRUGAPL-101
APL-101 (Vebreltinib) is an orally available small molecule, which is a tyrosine kinase inhibitor (TKI) for the mesenchymal epithelial transition protein tyrosine kinase receptor (c-Met) with high selectivity and potency. The treatments to be administered in this study include: • Treatment A (reference): Two 100 mg APL-101 (Vebreltinib) capsules (200 mg dose), manufactured for Apollomics, Inc.
DRUGPLB-1001
PLB-1001 (Bozitinib) is a chemical drug category 1.1 innovative drug. It is a highly effective and highly selective c-Met tyrosine kinase inhibitor. The treatments to be administered in this study include: • Treatment P (test): Two 100 mg PLB-1001 (Bozitinib) capsules (200 mg dose), manufactured for Beijing Pearl Biotechnology Co., Ltd.
Sponsors
Apollomics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
The treatment sequence will be determined using a 2×2 crossover design. This study includes an adaptive design feature of variable sample size.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Major Inclusion Criteria: * 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 1. * 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 1. Major
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration versus time curve (AUC) | 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 | Day 1 to Day 14 | Maximum observed plasma concentration (Cmax) after dosing of both treatments |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to the maximum observed plasma concentration | Day 1 to Day 14 | Time to the maximum observed plasma concentration (tmax) |
| Number of adverse events observed | Day 1 to Day 20-22 | Number of incidences of adverse events observed with respect to severity and relatedness to study treatment. |
| Apparent plasma terminal elimination half-life | Day 1 to Day 14 | Apparent plasma terminal elimination half-life (t1/2) after dosing of both treatments |
Countries
New Zealand
Contacts
Primary ContactYufei Chen, MS
Outcome results
None listed