A Clinical Trial to Evaluate a High-Fat Meal and Omeprazole Enteric-coated Tablets on ASBK021

A Single-Center, Open-Label, Multi-Cycle Study to Evaluate the Pharmacokinetic Profile of Different Doses of ABSK021 Capsules and the Effect of a High-Fat Meal and Omeprazole Enteric-coated Tablets on the Pharmacokinetic Profile of ABSK021 Capsules in Healthy Subjects

Part A: a single-center, randomized, open-label, three-cycle study to evaluate the pharmacokinetic (PK) profile of different doses of ABSK021 Capsules and the effect of a high-fat meal on the pharmacokinetic profile of ABSK021 Capsules in healthy subjects Part B: a single-center, open-label, fixed-sequence study to evaluate the effect of multiple oral doses of Omeprazole Enteric-coated Tablets on the PK profile of ABSK021 Capsules in healthy subjects

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: ABSK021; Drug: Omeprazole

Detailed Description

Part A: in this part, 18 healthy subjects are planned to be enrolled and will be randomized to either Study Sequence A (Sequence A) or Study Sequence B (Sequence B) (with 9 subjects in each sequence) to receive single oral dose of ABSK021 separately for a total of 3 doses, separated by 10 days.

Part B: in this part, 18 healthy subjects are planned to be enrolled to receive single oral dose of ABSK021 in a fixed sequence separately for a total of 2 doses. Subjects will receive a single dose of 50 mg ABSK021 Capsules on the morning of Cycle 1 Day 1 (C1D1) under fasting conditions; and 40 mg Omeprazole once daily from Days 1 to 5 of Cycle 2 (C2D1 to C2D5); with the other single oral dose of 50 mg ABSK021 received 2 h after the dose of Omeprazole under fasting conditions on C2D5

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuan Lu; Phone Number: 13700000000; Email: clinical@abbisko.cn
• Study Contact Backup: Name: kai Huang; Phone Number: 0510-85350951; Email: hk19820627@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy subjects aged 18 to 45 years (inclusive) at Screening;
2. Weight ≥ 50.0 kg (male) or ≥ 45.0 kg (female), with a body mass index (BMI) between 19.0 and 28.0 (inclusive), BMI = weight (kg)/height (m)2;
3. 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;
4. 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 (see section 5.4 for details), and male subjects should not donate sperm during such period; female subjects should not donate ovum during such period and should not be pregnant or lactating. Pregnancy period is defined as the period from the date of conception until termination of pregnancy, and will be determined by laboratory test of human chorionic gonadotropin (hCG) within 7 days prior to initiation of the study;
5. 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.

Exclusion Criteria:

1. Past or current medical history of chronic or severe conditions in cardiovascular, respiratory, blood, liver, kidney, gastrointestinal, endocrine or nervous systems;
2. Known or persistent mental disorders that may preclude the subject from participation in the study, as determined by the investigator;
3. Past history of gastric or intestinal surgery, or other operations (except for appendectomy) affecting the drug absorption;
4. Dysphagia and inability to take the investigational product orally;
5. Intolerant to venipuncture, difficult to collect blood samples, and fear of needle sickness and blood;
6. Known allergy to two or more kinds of foods and drugs; or allergic to ABSK021 or its excipients (lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, gelatin), allergic to omeprazole; and prone to allergic reactions such as rash and urticaria;
7. History of bacterial, fungal, parasitic, viral (excluding nasopharyngitis), mycobacterial infection, and COVID19 infection within 30 days prior to screening; or abnormal chest X-ray finding, assessed as clinically significant (by the investigator);
8. Symptoms of fatigue and pyrexia within 2 weeks prior to screening;
9. Abnormal laboratory tests: Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 1 × ULN; Creatinine > 1 × ULN; Total Bilirubin (TBIL) > 1.5 × ULN; Creatine Kinase (CK) > 1.5 × ULN; amylase > 1 × ULN; Lactate Dehydrogenase (LDH) > 1.5 × ULN; Serum Potassium < Lower Limit of Normal (LLN); and hemoglobin < LLN;
10. Positive result for either of the following tests: serum Hepatitis B Surface Antigen (HBsAg), Hepatitis B e Antigen (HBeAg), Hepatitis B e Antibody (HBeAb), Hepatitis B Core Antibody (HBcAb), Hepatitis C Virus (HCV) antibody, Human Immunodeficiency Virus (HIV) antibody, and treponema pallidum antibody;
11. Pregnant or lactating women, or those with a positive pregnancy test;
12. Participated in any clinical studies of drugs as a study subject and received the study drug within 3 months prior to screening;
13. Previously participated in any other study related to ABSK021 and received ABSK021;
14. Used strong inhibitors or inducers of CYP3A4 (including grapefruit juice, grapefruit hybrids, punica granatum, carambola, citrus maxima, and Seville oranges [including its juices or other processed products]; see Appendix 12.2Contraindicated Medications and Products for Concomitant Use with ABSK021 or Omeprazole for the detailed list) within 14 days prior to screening and at Screening;
15. Used strong inhibitors or inducers of CYP2C19 (including Fluoxetine, Fluvoxamine, Ticlopidine, Rifampin, etc., see Appendix 12.2 Contraindicated Medications and Products for Concomitant Use with ABSK021 or Omeprazole for the detailed list) within 14 days prior to screening and at Screening;
16. Have special diet requirements and cannot accept to take a unified dietary; specific dietary requirements: (i) the subjects can only eat the food provided by the study site during hospitalization, (ii) the subjects should avoid using strong inhibitors or inducers of CYP3A4 during the study, and (iii) the subjects should avoid using other strong inhibitors or inducers of CYP2C19 during the study (see Appendix 12.2 Contraindicated Medications and Products for Concomitant Use with ABSK021 or Omeprazole for the detailed list);
17. Consumption of more than 14 units of alcohol per week (1 unit of alcohol = about 360 mL of beer or 45 mL of spirits containing 40% alcohol or 150 mL of wine) within 3 months prior to signing the informed consent form, or a positive result for alcohol breath test on the day pre-dose (breath alcohol content > 0.0 mg/100 mL), or unable to abstain from alcohol during the study;
18. 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;
19. Positive for nicotine test;
20. Previous chronic consumption of excessive amount of tea, coffee, or caffeinated beverages (excessive intake is defined as taking more than 6 units of caffeine per day, 1 unit of caffeine equivalent to 177 mL of coffee, 355 mL of tea, 355 mL of cola, or 85 g of chocolate) or unable to abstain from caffeinated beverages during the study;
21. Known history of drug abuse or positive for drug abuse screening test (morphine, methamphetamine, ketamine, methylene dioxyamphetamine, and tetrahydrocannabinol acid);
22. Used over the counter or prescription drugs, including herbal medicine, health products, vitamins, and dietary supplements, within 14 days prior to screening, or plan to use such drugs during the study;
23. 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;
24. Received vaccine (including COVID19 vaccine) within 2 months prior to screening, or plan to get vaccinated during the study;
25. Significant abnormalities in vital signs, including: ear temperature > 37.7 °C; pulse rate > 100 beats/min or < 50 beats/min; systolic blood pressure ≥ 140 mmHg or < 90 mmHg, diastolic blood pressure ≥ 90 mmHg or < 50 mmHg;
26. Heart rate-corrected QT interval prolongation, QTcF > 450 ms (> 470 ms for females) (Note: QTc interval corrected using the Fridericia formula), or family history of long QT syndrome, or other clinically significant ECG abnormalities at Screening;
27. Plan to donate sperm or ovum within 6 months after administration of the investigational product;
28. Subjects involving in the design or conduct of this study and their immediate family members (e.g., employees of Abbisko Therapeutics Co., Ltd., employees of the CRO, and employees of the study site);
29. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABSK021	Drug: ABSK021; ABSK021 oral
Experimental: ABSK021and Omeprazole	Drug: ABSK021; ABSK021 oral; Drug: Omeprazole; Omeprazole oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	PK samples were collected according to the protocol requirements	predose up to 240 hours post-dose
tmax	PK samples were collected according to the protocol requirements	predose up to 240 hours post-dose
AUC0-∞	PK samples were collected according to the protocol requirements	predose up to 240 hours post-dose
AUClast	PK samples were collected according to the protocol requirements	predose up to 240 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE	The relationship of each adverse event to the investigational product will be assessed by CTCAE v5.0	up to 3 months
SAE	The relationship of each serious adverse event to the investigational product will be assessed by CTCAE v5.0	up to 3 months
blood pressure	blood pressure will be measured by sphygmomanometer	up to 1 months
respiratory rate	respiratory rate will be measured by respiratory rate machine	up to 1 months
ECG QT Interval	12-lead ECGs will be obtained during the study using an ECG machine	predose up to 240 hours post-dose
t1/2	PK samples were collected according to the protocol requirements	predose up to 240 hours post-dose
CL/F	PK samples were collected according to the protocol requirements	predose up to 240 hours post-dose
Vz/F	PK samples were collected according to the protocol requirements	predose up to 240 hours post-dose

Collaborators and Investigators

• Sponsor: Abbisko Therapeutics Co, Ltd
• Investigators: Principal Investigator: Kai Huang, No. 299, Qingyang Road, Wuxi City, Jiangsu Province

Study record dates

Study Major Dates

• Study Start (Estimated): March 28, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 29, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: ABSK021-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No