Clinical trial NCT05318820: A Clinical Study to Evaluate the Pharmacokinetics and Bioequivalence of HMPL-523 Tablets Produced by Two Different Manufacturers
Official title: A Phase I Monocentric, Open-label, Randomized, Crossover Clinical Study to Evaluate the Pharmacokinetics and Bioequivalence of HMPL-523 Tablets Produced by Two Different Manufacturers in Healthy Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy Subject
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2022-04-08
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a monocentric, randomized, open-label, single-dose, three-cycle, partial replicate clinical study designed to evaluate the pharmacokinetic profile and bioequivalence of HMPL-523 Tablets produced by two different manufacturers in healthy subjects. This study plans to enroll 39 healthy Chinese subjects who will be randomized (1:1:1) into one of three sequence groups (Test \[T\]/Reference\[R\]/R group, RTR group and RRT group) to receive a single dose in each cycle with a washout period of at least 7 days, where T is the test product \[i.e., HMPL-523 Tablets manufactured by Hutchison MediPharma (Suzhou) Limited.\], and R is the reference product (i.e., HMPL-523 Tablets manufactured by WuXi STA).
Primary purpose: OTHER

Brief summary: This is a monocentric, randomized, open-label, single-dose, three-cycle, partial replicate clinical study designed to evaluate the pharmacokinetic profile and bioequivalence of HMPL-523 Tablets produced by two different manufacturers in healthy subjects.

Detailed description: This is a monocentric, randomized, open-label, single-dose, three-cycle, partial replicate clinical study designed to evaluate the pharmacokinetic profile and bioequivalence of HMPL-523 Tablets produced by two different manufacturers in healthy subjects. This study plans to enroll 39 healthy Chinese subjects who will be randomized (1:1:1) into one of three sequence groups (Test \[T\]/Reference\[R\]/R group, RTR group and RRT group) to receive a single dose in each cycle with a washout period of at least 7 days, where T is the test product \[i.e., HMPL-523 Tablets manufactured by Hutchison MediPharma (Suzhou) Limited.\], and R is the reference product (i.e., HMPL-523 Tablets manufactured by WuXi STA).

The study includes three periods expected to last for 2 months: screening period, treatment period (for three cycles), and follow-up period

Eligibility criteria: Inclusion Criteria:

1. Subjects can communicate well with investigators, must be voluntary and sign the ICF, and agree to comply with the requirements in the study protocol;
2. Healthy male and female subjects aged 18-55 years (inclusive);
3. Weight ≥50 kg, Body Mass Index (BMI) between 19-26 kg/m2 (inclusive);
4. Subjects with good health condition
5. Subjects of childbearing potential must promise to use reliable contraceptive measures.

Exclusion Criteria:

1. History or clinical characterization of clinically significant metabolic/endocrine, hepatic, renal, hematological, pulmonary, immune, cardiovascular, gastrointestinal, genitourinary, neurological, or psychiatric diseases within 3 months prior to the screening period and in the screening period (judged by investigators);
2. creatinine clearance estimated using Cockcroft-Gault formula \[(140-age) × body weight (kg) × gender correction factor\] /\[0.818×Scr (umol/L)\] (male: 1.00, female: 0.85) \< 80 mL/min;
3. History of gastrointestinal surgery, kidney surgery, cholecystectomy and other surgeries that might affect drug absorption or excretion judged by the investigator;
4. History of serious allergy (e.g., drug allergy) and acute allergic rhinitis or food allergy, in particular allergy to the active ingredient or excipient of study drug, within two weeks prior to screening;
5. Previous history of hypertension;
6. Systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg;
7. Female subjects who have a positive pregnancy test;
8. Subjects who smoked \>10 cigarettes per day within 3 months prior to screening, or are unable to quit smoking completely during the study;
9. Subjects who drank on a regular basis within 6 months prior to the study, i.e., drinking more than 14 units of alcohol per week (1 unit =360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine);
10. Subjects with drug abuse (including but not limited to Morphine, 3,4-methylenedioxy-methamphetamine (MDMA), methamphetamine, tetrahydrocannabinolic acid, Ketamine, Cocaine or subjects whose urine drug abuse screen showed positive);
11. Use of blood products within 2 months before screening; donation of blood (including blood component) or loss of blood ≥400 mL within 3 months prior to screening, ≥200 mL within 1 month prior to screening, or plan to donate blood or blood component during the study or within 1 month after end of the study;
12. Subjects who have a fear of needles, hemophobia or whose venous blood is hard to collect;
13. Positive test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or treponema pallidum antibody;
14. Use of any prescription drug and Chinese herbal tonic within 30 days prior to the first dose;
15. Use of any over-the-counter drug (including but not limited to vitamins, prophylactic treatments, plant health products, etc.) within 14 days prior to the first dose;
16. Having participated in clinical trials for other drugs/medical devices within 3 months prior to screening;
17. Having consumed foods, juices and beverages containing alcohol, grapefruit, bigarade and caffeine within 72 hours prior to the first dose;
18. Subjects vaccinated with a live-attenuated vaccine within 8 weeks prior to screening or planning to get vaccinated during participation of this clinical trial;
19. Previous history of serious gastrointestinal disease, such as dysphagia, active gastric ulcer, inability to take drugs orally or absorption disorder for oral drugs;
20. Subjects who have special requirements for diet and cannot comply with uniform diet;
21. Lactating female subjects;
22. According to the investigator's judgment, the subjects had any other disease or status that might affect the normal completion of the study or the evaluation of the study data, or had any other condition that was not suitable for the study.

Primary outcomes:
measure: maximum plasma concentration (Cmax)
timeFrame: through study completion, an average of 2 months
measure: time to maximum plasma concentration (Tmax)
timeFrame: Time Frame: through study completion, an average of 2 months
measure: terminal elimination half-life (t1/2)
timeFrame: through study completion, an average of 2 months
measure: Area under plasma drug concentration-time curve (AUC0-t, AUC0-∞)
timeFrame: through study completion, an average of 2 months
Secondary outcomes:
measure: Ratio between AUCs of two HMPL-523 Tablets
timeFrame: through study completion, an average of 2 months
measure: safety information/AE,SAE
timeFrame: through study completion, an average of 2 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Xuhui Central Hospital
Study officials:
affiliation: Shanghai Xuhui Central Hospital
name: Jingying Jia
role: PRINCIPAL_INVESTIGATOR
References: