Pharmacokinetics and Bioequivalence Study of HMPL-523 Acetate Tablets in Humans

Overview

Two formulations containing the same active pharmaceutical ingredient are considered bioequivalent if their relative bioavailability (rate and extent of drug absorption) falls within acceptable predetermined limits after administration at the same molar dose. Formulations with bioequivalence are considered to act comparably in vivo, i.e., similar in terms of safety and efficacy. This study aims to evaluate the pharmacokinetic (PK) profile and bioequivalence of the original and modified formulations of HMPL-523 acetate tablets in healthy participants to bridge the safety and efficacy of the modified formulation of HMPL 523 acetate tablets in humans.

This study adopts a single-center, randomized, open-label, single-dose, four-cycle, fully replicate clinical trial design to evaluate the PK profile and bioequivalence of two different formulations of HMPL-523 acetate tablets in healthy participants. In this study, a total of 54 Chinese healthy participants are planned to be enrolled and randomly assigned to 2 dosing sequence groups (TRTR, and RTRT) in a 1:1 ratio, and administered once per cycle, with a washout period of at least 7 days, where T is the test formulation (the modified formulation) and R is the reference formulation (the original formulation). The study will be divided into 3 periods: screening/baseline period, dosing period (four cycles), and follow-up period. The entire study from the screening period to the follow-up period is expected to last approximately 2 months. Screening Period/Baseline Period The trial participants will sign a written informed consent form (ICF) on a voluntary basis prior to screening. Screening period/baseline period assessment will be completed within 14 days prior to the first dose. At screening/baseline, demographic data, medical history, medication history, allergy history, blood donation history, and participation in clinical trials should be collected, and physical examination, vital sign measurements, alcohol breath test, urine drug abuse screening, 12-lead ECG, infection markers \[including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, and Treponema pallidum antibody\], laboratory tests (including hematology, blood chemistry, coagulation test, urinalysis), pregnancy test (female) and chest X-ray (frontal and lateral) examination will be performed. Only serious adverse events (SAEs) will be collected at screening/baseline. Dosing Period (4 cycles) Eligible participants upon preliminary screening will be required to be admitted to the site 3 days before the first dose (i.e., 3 days prior to the initiation of the first cycle of medication). On the day of admission, vital sign measurements and inquiry about recent diet and medication, and pregnancy test (females only) will be performed to further verify the inclusion and exclusion criteria. According to the randomization scheme, eligible participants upon screening will be assigned a random number and randomly assigned to different dosing sequences (TRTR or RTRT). Based on the randomized dosing regimen, participants in different groups will take the test formulation or the reference formulation respectively after intake of breakfast (standard meal) on the first day of each cycle. The dosing regimen is detailed in the table below. Crossover dosing regimen Group Number of participants Intake of standard meal breakfast Cycle 1 Cycle 2 Cycle 3 Cycle 4 TRTR 27 T R T R RTRT 27 R T R T Method of administration: Participants will fast for at least 10 hours before a standard meal on the first day of each cycle, start having a standard meal 30 minutes before dosing, and finish the meal within 25 minutes. After the meal, participants will have blank blood samples collected, and take the medication with about 240 mL of water on time 30 minutes after the meal. Except for the above-mentioned water for medication, participants are deprived of water is prohibited from 1 hour prior to the medication to 1 hour after the medication, and deprived of food within 4 hours after the medication. During hospitalization, the diet of the participants will be provided by the site. The dosing period consists of four cycles, and the scheduled PK blood sampling time points for each participant in each cycle is as follows: within 0.5 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, 72 hours post-dose, with a total of 18 collections (see Table 2 for details), and about 3 mL of venous blood collected each time. After the participants are admitted to the clinical study ward, the vital sign measurements will be performed 1 day pre-dose in each cycle and 3±1 hours post-dose on the first day of each cycle. In addition, vital sign measurements, blood chemistry, and hematology will be performed on the Day 4 of the each of the first three cycles. On Cycle 4 Day 4, the participants will be discharged after vital sign measurements, physical examination, laboratory tests, and 12-lead ECG examination are completed. Follow-up Period Participants will be followed up to Day 12±2 after the last dose (the day of the last dose is defined as Day 1 of follow-up period). The investigator will collect all AEs and concomitant medications/therapies from the participants during this period through telephone calls (or other means such as text messages). If there are AEs ongoing at follow-up, follow-up will continue until return to normal level, abnormal, not clinically significant, baseline level, stable or lost to follow-up, or refusal to visit, etc.,