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

NCT05642377 | Recruiting Phase 1

• 1 other identifier: HGR4113-P1-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

1. 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. 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

Outcome Measures

Primary Outcomes (14)

• Safety and Tolerability Assessment by Adverse Event Monitoring

  Number of participants with observed adverse events

  Day 1 to 7 days after day of last administration

• Safety and Tolerability Assessment by Number of Patients with Change in Physical Examination

  Number of participants with clinically significant change in physical examination

  Day 1 to 7 days after day of last administration

• Safety and Tolerability Assessment by Number of Participants with Change in Vital Signs

  Number of participants with clinically significant change in vital signs including blood pressure, heart rate, and body temperature

  Day 1 to 7 days after day of last administration

• Safety and Tolerability Assessment by Number of Participants with Change in Laboratory Test

  Number of participants with clinically significant change in laboratory test assessed through hematology, blood biochemistry, urinalysis, blood coagulation, and hormone tests

  Day 1 to 7 days after day of last administration

• Safety and Tolerability Assessment by Number of Participants with Change in 12-Lead Electrocardiogram

  Number of participants with clinically significant change in 12-lead electrocardiogram

  Day 1 to 7 days after day of last administration

• Safety and Tolerability Assessment by Number of Participants with Change in Semen Parameters

  Number of participants with clinically significant change in semen assessed through semen volume, semen pH, sperm count, sperm concentration, sperm motility, and sperm morphology

  From Screening to 12 weeks after day of last administration

• Pharmacokinetic Assessment by Maximum Plasma Concentration of HGR4113

  Maximum Plasma Concentration of HGR4113 (Cmax)

  Hour 0 to 96

• Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HGR4113 Over Dosing Interval

  Area Under the Plasma Concentration-Time Curve of HGR4113 Over Dosing Interval (AUCtau)

  Hour 0 to 24

• Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HGR4113 from Time Zero to the Last Measurable Point

  Area Under the Plasma Concentration-Time Curve of HGR4113 from Time Zero to the Last Measurable Point (AUClast)

  Hour 0 to 96

• Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HGR4113 from Time Zero to Infinity

  Area Under the Plasma Concentration-Time Curve of HGR4113 from Time Zero to Infinity (AUCinf)

  Hour 0 to 96

• Pharmacokinetic Assessment by Half-Life of HGR4113

  Half-life of HGR4113 (T1/2)

  Hour 0 to 96

• Pharmacokinetic Assessment by Time to Maximum Observed Plasma Concentration of HGR4113

  Time to Maximum Observed Plasma of HGR4113 (Tmax)

  Hour 0 to 96

• Pharmacokinetic Assessment by Oral Clearance of HGR4113

  Oral Clearance of HGR4113 (CL/F)

  Hour 0 to 96

• Pharmacokinetic Assessment by Apparent Volume of Distribution of HGR4113

  Volume of Distribution of HGR4113 (Vz/F)

  Hour 0 to 96

Secondary Outcomes (5)

• Pharmacodynamic Assessment by Change in Paraoxonase 1 Activity

  Day -1 to 17

• Pharmacodynamic Assessment by Change in Plasma Glucose

  Day -1 to 17

• Pharmacodynamic Assessment by Change in Plasma HbA1c

  Day -1 to 17

• Pharmacodynamic Assessment by Change in Plasma Insulin

  Day -1 to 17

• Pharmacodynamic Assessment by Change in Plasma C-peptide

  Day -1 to 17

Study Arms (10)

HGR4113 300 mg Single Dose

EXPERIMENTAL

Single oral dosing of HGR4113 300 mg

Drug: HGR4113

Placebo 300 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of placebo 300 mg

Drug: Placebo

HGR4113 600 mg Single Dose

EXPERIMENTAL

Single oral dosing of HGR4113600 mg

Drug: HGR4113

Placebo 600 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of placebo 600 mg

Drug: Placebo

HGR4113 1200 mg Single Dose

EXPERIMENTAL

Single oral dosing of HGR41131200 mg

Drug: HGR4113

Placebo 1200 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of placebo 1200 mg

Drug: Placebo

HGR4113 200 mg Multiple Dose

EXPERIMENTAL

Multiple oral dosing of HGR4113 200 mg, twice daily

Drug: HGR4113

Placebo 200 mg Multiple Dose

PLACEBO COMPARATOR

Multiple oral dosing of placebo 200 mg, twice daily

Drug: Placebo

HGR4113 400 mg Multiple Dose

EXPERIMENTAL

Multiple oral dosing of HGR4113 400 mg, twice daily

Drug: HGR4113

Placebo 400 mg Multiple Dose

PLACEBO COMPARATOR

Multiple oral dosing of placebo 400 mg, twice daily

Drug: Placebo

Interventions

HGR4113 DRUG

Once-daily oral administration

HGR4113 1200 mg Single Dose; HGR4113 300 mg Single Dose; HGR4113 600 mg Single Dose

Placebo DRUG

Once-daily oral administration

Placebo 1200 mg Single Dose; Placebo 300 mg Single Dose; Placebo 600 mg Single Dose

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to comprehend and willing to sign an informed consent form approved by the IRB before Screening.
• Adult volunteers between 19 and 50 years of age at Screening.
• Body mass index (BMI) between 18.0 and 24.9.
• ☞ BMI (kg/m\^2) = body weight (kg) / (height \[m\])\^2
• 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.

You may not qualify if:

• 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).
• 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.
• Significant history or clinical manifestation of hypersensitivity to any drug including licorice or other drug (e.g., aspirin, antibiotics).
• 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).
• 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.
• History of drug/chemical abuse or tested positive in urine drug screen.
• 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.
• Participation in any clinical study or bioequivalence study within 6 months prior to dosing.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Glaceum: lead
• Seoul National University Hospital: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Kyung Sang Yu, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Youngah Kim

CONTACT

82-31-8002-2558; yakim116@glaceum.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: December 8, 2022
• Study Start: November 22, 2022
• Primary Completion: July 31, 2024
• Study Completion: January 31, 2025
• Last Updated: March 21, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)