To Evaluate the Safety, Pharmacokinetic and the Effect of Food After Administration of ABN401 in Healthy Adult Volunteers

An Open-label, Randomized, Crossover Phase 1 Clinical Trial to Evaluate the Safety, Pharmacokinetic Characteristics and the Effect of Food After Administration of ABN401 in Healthy Adult Volunteers

This randomized open-label, two-way crossover study is designed to evaluate the safety and pharmacokinetic characteristics of ABN401, and the effect of high-fat meal on the pharmacokinetic profiles of ABN401 and its metabolites in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Other: High-fat meal (over 900 kcal); Drug: ABN401 (investigational product)

Detailed Description

The amount of dose for a single administration is 800 mg, which will be given as three 250 mg tablets and two 25 mg tablets.

• Fasting: Single oral administration of ABN401 800 mg (3 x 250 mg + 2 x 25 mg) after an overnight fast
• Fed: Single oral administration of ABN401 800 mg (3 x 250 mg + 2 x 25 mg) in fed condition. High-fat meal (over 900kcal with over 35 percent fat content of total calorie) will be provided prior to IP administration. The IP will then be administered 30 minutes after the subject begins the meal.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seowon-gu
    • Cheongju-si, Seowon-gu, Korea, Republic of
      • Chungbuk National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy subjects aged over 19 years (inclusive) at the time of screening

2. Subjects weighing at least 50.0 kg with a BMI between 18.0 kg/m2 and 30.0 kg/m2 (inclusive)

   ☞ BMI (body mass index) = {weight (kg) / height (m)2}

3. Subjects with neither congenital nor chronic diseases requiring treatment, and no abnormal symptoms or findings upon medical examination
4. Subjects considered eligible for the study participation in accordance to the results of vital signs, 12-lead ECG, clinical laboratory tests (including hematology, blood chemistry, urinalysis, serology, etc.) and urine drug screening conducted at the time of screening, based on the investigational product (IP) characteristics (In cases of the results outside the NCS range considered due to irregular lifestyle (drinking, night-time shifts, etc.) final decision of inclusion can be made with additional follow-up after modification of the causal lifestyle)
5. Subjects who has a full understanding in participation of the study, voluntarily provide a written consent in participation, and give full agreement in following the subject guidelines throughout the entire study period

Exclusion Criteria:

1. Subjects with any clinically significant hepatic, renal, nervous, psychiatric, respiratory, endocrine, circulatory system, neoplastic, genitourinary, cardiovascular, digestive, musculoskeletal systemic diseases, or a past medical history of any of the aforementioned conditions.
2. Subjects with a past medical history of gastrointestinal disease (Crohn's disease, ulcers, acute/chronic pancreatitis, etc.) or gastrointestinal surgeries (except for simple appendectomy and hernia repair) which may affect the absorption of the IP.

3. Subjects with clinically significant 12-lead ECG findings including the following results at the time of screening.

   • QTc > 450 ms
   • PR interval > 200 ms
   • QRS duration > 120 ms
4. Subjects with SBP ≥ 150 mmHg or ≤ 90 mmHg; DBP ≥ 100 mmHg or ≤ 60 mmHg; PR ≤ 40 beat/min or ≥ 100 beat/min, when measured in a seated position without an abrupt change in body position for at least 3 minutes.

5. Subjects with laboratory test results as follows.

   • Liver function test (AST, ALT, ALP, γ-GTP and total bilirubin) values exceeding twice the upper limit of normal.
   • Creatinine values outside the reference ranges or eGFR < 60 mL/min/1.73m2
6. Subjects who have participated and given any other study drugs in other clinical study or bioequivalence study within 6 months prior to the first IP administration (the last day of IP administration is considered the end-of-study).
7. Subjects with a past history of drug abuse or a positive urine drug screening test.
8. Subjects taking drugs known to significantly induce or inhibit drug metabolizing enzymes, including barbitals, within 1 month prior to the first IP administration.
9. Subjects who have taken any prescribed medications or herbal medicine within 2 weeks or any over-the-counter medications or vitamin supplements within 10 days prior to the first IP administration (except for circumstances considered acceptable with no concerned effect on the pharmacokinetics of the IP at the investigator's discretion).
10. Subjects with hypersensitivity reactions or a clinically significant medical history of hypersensitivity reactions to drug substances and additives or other drugs (such as aspirin, anti-biotics, biguanides, etc.).
11. Subjects who have donated whole blood within 2 months or blood components within 1 month or received a blood transfusion within 1 month prior to the first IP administration.

12. Subjects who have consistently drunk alcohol within 6 months exceeding 21 units/week (1 unit= 10 g) prior to the first IP administration or are unable to refrain from drinking from the time of consent until PSV.

    *Alcohol consumption (g) = amount (mL) x alcohol by volume (%) x 0.8* (*pure alcohol 10 g = 12.5 mL)

13. Subjects who have smoked more than 10 cigarettes/day on average 3 months prior to the first IP administration and are unable to oblige the no-smoking rules from 24 hours prior to the first IP administration until the last blood sampling point.
14. Subjects unable to refrain from consuming grapefruit-containing food or beverages from 48 hours prior to the first IP administration until PSV.
15. Subjects unable to refrain from consuming caffeine-containing food or beverages (coffee, green tea, black tea, carbonated drinks, coffee-flavored milk, energy drinks, etc.) from 24 hours prior to the first IP administration until the last blood sampling point.
16. Subjects unable to refrain from vigorous exercise which exceeds daily routine from 48 hours prior to the first IP administration until PSV.
17. Subjects following an unusual diet or unable to consume meals provided during the study.
18. Pregnant subjects with a positive urine HCG test, or lactating female subjects.
19. Subjects who are planning for pregnancy or not willing to use a medically reliable forms of contraception (administration of contraceptives or transplantation of contraceptives or use of an intrauterine device, infertility surgery (vasectomy or tubule ligation), and physical barriers (spermicide, condom, contraceptive diaphragm, vaginal sponge used with a cervical cap)) from the time of consent until 3months after the last IP administration.
20. Subjects otherwise considered ineligible for participation due to other reasons including clinical laboratory test results not mentioned in the exclusion criteria at the investigator's discretion.

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
Other: Fasting group; Period 1 : Single oral administration of ABN401 800 mg (3 x 250 mg + 2 x 25 mg) after an overnight fast Peroid 2: Single oral administration of ABN401 800 mg (3 x 250 mg + 2 x 25 mg) in fed condition. High-fat meal (over 900 kcal)	Other: High-fat meal (over 900 kcal); High-fat meal (over 900 kcal with over 35 percent fat content of total calorie) will be provided prior to IP administration. The IP will then be administered 30 minutes after the subject begins the meal.; Drug: ABN401 (investigational product); The investigational product, ABN401 800 mg (3 x 250 mg + 2 x 25 mg) will be administered orally with approximately 240 mL of water in fasted or fed condition in accordance with the order of IP administration in an allocated sequence.
Other: Fed group; Peroid 1: Single oral administration of ABN401 800 mg (3 x 250 mg + 2 x 25 mg) in fed condition. High-fat meal (over 900 kcal) Period 2: Single oral administration of ABN401 800 mg (3 x 250 mg + 2 x 25 mg) after an overnight fast	Other: High-fat meal (over 900 kcal); High-fat meal (over 900 kcal with over 35 percent fat content of total calorie) will be provided prior to IP administration. The IP will then be administered 30 minutes after the subject begins the meal.; Drug: ABN401 (investigational product); The investigational product, ABN401 800 mg (3 x 250 mg + 2 x 25 mg) will be administered orally with approximately 240 mL of water in fasted or fed condition in accordance with the order of IP administration in an allocated sequence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t	AUC0-t of ABN401	Pre-dose (0 hour), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
Cmax	Cmax of ABN401	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	Tmax of ABN401	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
AUCinf	AUCinf of ABN401	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
t1/2	t1/2 of ABN401	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
CL/F	CL/F of ABN401	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
Vd/F	Vd/F of ABN401	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24h hours (h)post-dose
AUC0-t	AUC0-t of ABN401 Metabolite	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
Cmax	Cmax of ABN401 Metabolite	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
Tmax	Tmax of ABN401 Metabolite	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
AUCinf	AUCinf of ABN401 Metabolite	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
t1/2	t1/2 of ABN401 Metabolite	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose
Metabolic ratio	Metabolic ratio of ABN401	Pre-dose (0 h), 0.25 hours (h), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, and 24 hours (h) post-dose

Collaborators and Investigators

• Sponsor: Abion Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2022
• Primary Completion (Actual): February 18, 2022
• Study Completion (Actual): October 18, 2022

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: February 18, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: ABN401-002

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