A Study to Investigate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Food Effect of HGR4113 in Healthy Subjects

NCT ID: NCT05642377

Last Updated: 2024-03-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-22
• Study Completion Date: 2025-01-31

Brief Summary

1. Study Objective: The objective of this study is to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic characteristics, and food effect of HGR4113 after single and multiple oral administration in healthy subjects.

2. Study Design and Plan: This study is a randomized, double-blind, placebo controlled, single and multiple dosing, dose-escalation phase 1 clinical trial. Volunteers who have been deemed eligible based on the inclusion/exclusion criteria will be given a random number. Each subject will be assigned to one of the dose groups in a 6:2 ratio to HGR4113 (active) or placebo. Subjects will be studied in a double-blind manner and will receive the investigational product per protocol. Dose will be escalated once safety data is collected up to the last pharmacokinetic blood collection timepoint and safety and tolerability has been deemed acceptable following the review of the Safety Review Committee. Assessments including vital signs, 12-lead ECG, clinical laboratory, reproductive hormones, physical examination, and monitoring of adverse events concomitant medications will be conducted to evaluate safety and tolerability. Blood will be collected to evaluate the pharmacokinetic/pharmacodynamic characteristics.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

HGR4113 300 mg Single Dose

Single oral dosing of HGR4113 300 mg

Group Type: EXPERIMENTAL

HGR4113

Intervention Type: DRUG

Once-daily oral administration

Placebo 300 mg Single Dose

Single oral dosing of placebo 300 mg

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Once-daily oral administration

HGR4113 600 mg Single Dose

Single oral dosing of HGR4113600 mg

Group Type: EXPERIMENTAL

HGR4113

Intervention Type: DRUG

Once-daily oral administration

Placebo 600 mg Single Dose

Single oral dosing of placebo 600 mg

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Once-daily oral administration

HGR4113 1200 mg Single Dose

Single oral dosing of HGR41131200 mg

Group Type: EXPERIMENTAL

HGR4113

Intervention Type: DRUG

Once-daily oral administration

Placebo 1200 mg Single Dose

Single oral dosing of placebo 1200 mg

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Once-daily oral administration

HGR4113 200 mg Multiple Dose

Multiple oral dosing of HGR4113 200 mg, twice daily

Group Type: EXPERIMENTAL

HGR4113

Intervention Type: DRUG

Twice-daily oral administration

Placebo 200 mg Multiple Dose

Multiple oral dosing of placebo 200 mg, twice daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Twice-daily oral administration

HGR4113 400 mg Multiple Dose

Multiple oral dosing of HGR4113 400 mg, twice daily

Group Type: EXPERIMENTAL

HGR4113

Intervention Type: DRUG

Twice-daily oral administration

Placebo 400 mg Multiple Dose

Multiple oral dosing of placebo 400 mg, twice daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Twice-daily oral administration

Interventions

HGR4113

Once-daily oral administration

Intervention Type: DRUG

Placebo

Once-daily oral administration

Intervention Type: DRUG

HGR4113

Twice-daily oral administration

Intervention Type: DRUG

Placebo

Twice-daily oral administration

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Able to comprehend and willing to sign an informed consent form approved by the IRB before Screening.

2. Adult volunteers between 19 and 50 years of age at Screening.

3. Body mass index (BMI) between 18.0 and 24.9.

☞ BMI (kg/m^2) = body weight (kg) / (height [m])^2

4. In good health, determined by no clinically significant findings from medical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory tests at Screening, or subjects who are deemed acceptable by the Investigator regardless of the test results.

Exclusion Criteria

1. Significant history or clinical manifestation of any hepatic, kidney, neurological, immune, respiratory, endocrine, hematological, neoplastic, or cardiovascular disease, or psychiatric disorder (e.g., mood disorder, obsessive-compulsive disorder).

2. History of stomach or intestinal disorders (e.g., Chron's disease, ulcer) or surgeries - not including appendectomy, hemorrhoidectomy, or herniotomy - which may affect the safety or pharmacokinetic/pharmacodynamic evaluation of the investigational product.

3. Significant history or clinical manifestation of hypersensitivity to any drug including licorice or other drug (e.g., aspirin, antibiotics).

4. One or more of the following laboratory test results at Screening:

• ANC < 1000
• AST, ALT, GGT, total bilirubin > 1.5x upper limit normal
• Fasting glucose ≥ 126 mg/dL or HbA1c ≥ 6.5% despite two retests
• eGFR < 60 (CKD-EPI).

5. Systolic blood pressure < 90 mmHg or > 150 mmHg, or diastolic blood pressure < 60 mgHg or > 100 mmHg as determined by vital signs monitored after resting in sitting position for at least 3 minutes.

6. History of drug/chemical abuse or tested positive in urine drug screen.

7. Used or intend to use any prescription medications/products or phytotherapeutic/herbal/plant-derived preparations within 14 days prior to dosing, or any nonprescription medications/products (i.e., over-the-counter (OTC) drugs), health products, or vitamins within 7 days prior to dosing, unless deemed acceptable by the Investigator.

8. Participation in any clinical study or bioequivalence study within 6 months prior to dosing.

9. Whole blood donation within 2 months prior to dosing, plasma/platelet donation within 1 month prior to dosing, or receipt of blood products within 1 month prior to dosing.

10. Alcohol consumption > 21 units/week (1 unit = 10 g of pure alcohol) or unable to abstain from consuming alcohol 3 days prior to first dosing until the last pharmacokinetic blood sampling.

11. History of smoking within 90 days prior to dosing (however, participation is acceptable if the subject has quit at least 90 days prior to dosing) or unable to abstain from smoking 90 days prior to dosing until the last pharmacokinetic blood sampling.

12. Ingestion of grapefruit-containing foods or beverages 24 hours 3 days prior to dosing until the last pharmacokinetic blood sampling, or unable to abstain from ingesting such foods or beverages during the same period.

13. Unable to abstain from ingesting caffeine-containing foods or beverages (e.g., coffee, tea [e.g., black tea, green tea], soft drinks, coffee milk, energy drinks, sports drinks) 3 days prior to dosing until the last pharmacokinetic blood sampling.

14. Females, excluding those who have amenorrhea for at least 12 months or have been surgically sterilized (e.g., bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), who are pregnant or lactating, evidenced by a positive urine hCG pregnancy test.

15. Subject or subject's partner is unable or unwilling to use a medically acceptable means of contraception during and for 90 days following the last dosing or willing to donate sperm during the same period.

• Acceptable contraceptive methods include:
• Use of an intrauterine device that has been proven highly effective
• Male or female physical contraceptive used with chemical sterilization
• Surgical sterilization of the subject or the subject's partner (e.g., vasectomy, hysterectomy, tubal ligation, salpingectomy).

16. Subjects who, in the opinion of the Investigator, should not participate in in this study based on other reasons.

17. Subject who is confirmed as the CYP2C19 poor metabolizer (e.g., *2/*2, *2/*3, *3/*3) by exploratory genotyping test at Screening in MAD group.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: collaborator

Glaceum

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kyung Sang Yu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

Seoul National University Hospital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Youngah Kim

Role: CONTACT

yakim116@glaceum.com

82-31-8002-2558

Facility Contacts

Kyung Sang Yu, MD, PhD

Role: primary

Other Identifiers

HGR4113-P1-01

Identifier Type: -

Identifier Source: org_study_id