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

Primary Purpose

Diabetes Mellitus, Type 2

Status
Recruiting
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
HGR4113
Placebo
Sponsored by
Glaceum
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

19 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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. 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. 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. 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. 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). Subjects who, in the opinion of the Investigator, should not participate in in this study based on other reasons.

Sites / Locations

  • Seoul National University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

HGR4113 300 mg Single Dose

Placebo 300 mg Single Dose

HGR4113 600 mg Single Dose

Placebo 600 mg Single Dose

HGR4113 1200 mg Single Dose

Placebo 1200 mg Single Dose

HGR4113 300 mg Multiple Dose

Placebo 300 mg Multiple Dose

HGR4113 600 mg Multiple Dose

Placebo 600 mg Multiple Dose

HGR4113 1200 mg Multiple Dose

Placebo 1200 mg Multiple Dose

Arm Description

Single oral dosing of HSG4112 300 mg

Single oral dosing of placebo 300 mg

Single oral dosing of HSG4112 600 mg

Single oral dosing of placebo 600 mg

Single oral dosing of HSG4112 1200 mg

Single oral dosing of placebo 1200 mg

Multiple oral dosing of HSG4112 300 mg

Multiple oral dosing of placebo 300 mg

Multiple oral dosing of HSG4112 600 mg

Multiple oral dosing of placebo 600 mg

Multiple oral dosing of HSG4112 1200 mg

Multiple oral dosing of placebo 1200 mg

Outcomes

Primary Outcome Measures

Safety and Tolerability Assessment by Adverse Event Monitoring
Number of participants with observed adverse events
Safety and Tolerability Assessment by Number of Patients with Change in Physical Examination
Number of participants with clinically significant change in physical examination
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
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
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
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
Pharmacokinetic Assessment by Maximum Plasma Concentration of HGR4113
Maximum Plasma Concentration of HGR4113 (Cmax)
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)
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)
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)
Pharmacokinetic Assessment by Half-Life of HGR4113
Half-life of HGR4113 (T1/2)
Pharmacokinetic Assessment by Time to Maximum Observed Plasma Concentration of HGR4113
Time to Maximum Observed Plasma of HGR4113 (Tmax)
Pharmacokinetic Assessment by Oral Clearance of HGR4113
Oral Clearance of HGR4113 (CL/F)
Pharmacokinetic Assessment by Apparent Volume of Distribution of HGR4113
Volume of Distribution of HGR4113 (Vz/F)

Secondary Outcome Measures

Pharmacodynamic Assessment by Change in Paraoxonase 1 Activity
Change in paraoxonase 1 activity
Pharmacodynamic Assessment by Change in Plasma Glucose
Change in plasma glucose level
Pharmacodynamic Assessment by Change in Plasma HbA1c
Change in plasma HbA1c level
Pharmacodynamic Assessment by Change in Plasma Insulin
Change in plasma insulin level
Pharmacodynamic Assessment by Change in Plasma C-peptide
Change in plasma c-peptide level

Full Information

First Posted
November 30, 2022
Last Updated
November 30, 2022
Sponsor
Glaceum
Collaborators
Seoul National University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05642377
Brief Title
A Study to Investigate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Food Effect of HGR4113 in Healthy Subjects
Official Title
A Randomized, Double-Blind, Placebo Controlled, Single and Multiple Dosing, Dose-Escalation Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Food Effect After Oral Administration of HGR4113 in Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 22, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Glaceum
Collaborators
Seoul National University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HGR4113 300 mg Single Dose
Arm Type
Experimental
Arm Description
Single oral dosing of HSG4112 300 mg
Arm Title
Placebo 300 mg Single Dose
Arm Type
Placebo Comparator
Arm Description
Single oral dosing of placebo 300 mg
Arm Title
HGR4113 600 mg Single Dose
Arm Type
Experimental
Arm Description
Single oral dosing of HSG4112 600 mg
Arm Title
Placebo 600 mg Single Dose
Arm Type
Placebo Comparator
Arm Description
Single oral dosing of placebo 600 mg
Arm Title
HGR4113 1200 mg Single Dose
Arm Type
Experimental
Arm Description
Single oral dosing of HSG4112 1200 mg
Arm Title
Placebo 1200 mg Single Dose
Arm Type
Placebo Comparator
Arm Description
Single oral dosing of placebo 1200 mg
Arm Title
HGR4113 300 mg Multiple Dose
Arm Type
Experimental
Arm Description
Multiple oral dosing of HSG4112 300 mg
Arm Title
Placebo 300 mg Multiple Dose
Arm Type
Placebo Comparator
Arm Description
Multiple oral dosing of placebo 300 mg
Arm Title
HGR4113 600 mg Multiple Dose
Arm Type
Experimental
Arm Description
Multiple oral dosing of HSG4112 600 mg
Arm Title
Placebo 600 mg Multiple Dose
Arm Type
Placebo Comparator
Arm Description
Multiple oral dosing of placebo 600 mg
Arm Title
HGR4113 1200 mg Multiple Dose
Arm Type
Experimental
Arm Description
Multiple oral dosing of HSG4112 1200 mg
Arm Title
Placebo 1200 mg Multiple Dose
Arm Type
Placebo Comparator
Arm Description
Multiple oral dosing of placebo 1200 mg
Intervention Type
Drug
Intervention Name(s)
HGR4113
Intervention Description
Once-daily oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Once-daily oral administration
Primary Outcome Measure Information:
Title
Safety and Tolerability Assessment by Adverse Event Monitoring
Description
Number of participants with observed adverse events
Time Frame
Day 1 to 7 days after day of last administration
Title
Safety and Tolerability Assessment by Number of Patients with Change in Physical Examination
Description
Number of participants with clinically significant change in physical examination
Time Frame
Day 1 to 7 days after day of last administration
Title
Safety and Tolerability Assessment by Number of Participants with Change in Vital Signs
Description
Number of participants with clinically significant change in vital signs including blood pressure, heart rate, and body temperature
Time Frame
Day 1 to 7 days after day of last administration
Title
Safety and Tolerability Assessment by Number of Participants with Change in Laboratory Test
Description
Number of participants with clinically significant change in laboratory test assessed through hematology, blood biochemistry, urinalysis, blood coagulation, and hormone tests
Time Frame
Day 1 to 7 days after day of last administration
Title
Safety and Tolerability Assessment by Number of Participants with Change in 12-Lead Electrocardiogram
Description
Number of participants with clinically significant change in 12-lead electrocardiogram
Time Frame
Day 1 to 7 days after day of last administration
Title
Safety and Tolerability Assessment by Number of Participants with Change in Semen Parameters
Description
Number of participants with clinically significant change in semen assessed through semen volume, semen pH, sperm count, sperm concentration, sperm motility, and sperm morphology
Time Frame
From Screening to 12 weeks after day of last administration
Title
Pharmacokinetic Assessment by Maximum Plasma Concentration of HGR4113
Description
Maximum Plasma Concentration of HGR4113 (Cmax)
Time Frame
Hour 0 to 96
Title
Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HGR4113 Over Dosing Interval
Description
Area Under the Plasma Concentration-Time Curve of HGR4113 Over Dosing Interval (AUCtau)
Time Frame
Hour 0 to 24
Title
Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HGR4113 from Time Zero to the Last Measurable Point
Description
Area Under the Plasma Concentration-Time Curve of HGR4113 from Time Zero to the Last Measurable Point (AUClast)
Time Frame
Hour 0 to 96
Title
Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HGR4113 from Time Zero to Infinity
Description
Area Under the Plasma Concentration-Time Curve of HGR4113 from Time Zero to Infinity (AUCinf)
Time Frame
Hour 0 to 96
Title
Pharmacokinetic Assessment by Half-Life of HGR4113
Description
Half-life of HGR4113 (T1/2)
Time Frame
Hour 0 to 96
Title
Pharmacokinetic Assessment by Time to Maximum Observed Plasma Concentration of HGR4113
Description
Time to Maximum Observed Plasma of HGR4113 (Tmax)
Time Frame
Hour 0 to 96
Title
Pharmacokinetic Assessment by Oral Clearance of HGR4113
Description
Oral Clearance of HGR4113 (CL/F)
Time Frame
Hour 0 to 96
Title
Pharmacokinetic Assessment by Apparent Volume of Distribution of HGR4113
Description
Volume of Distribution of HGR4113 (Vz/F)
Time Frame
Hour 0 to 96
Secondary Outcome Measure Information:
Title
Pharmacodynamic Assessment by Change in Paraoxonase 1 Activity
Description
Change in paraoxonase 1 activity
Time Frame
Day -1 to 17
Title
Pharmacodynamic Assessment by Change in Plasma Glucose
Description
Change in plasma glucose level
Time Frame
Day -1 to 17
Title
Pharmacodynamic Assessment by Change in Plasma HbA1c
Description
Change in plasma HbA1c level
Time Frame
Day -1 to 17
Title
Pharmacodynamic Assessment by Change in Plasma Insulin
Description
Change in plasma insulin level
Time Frame
Day -1 to 17
Title
Pharmacodynamic Assessment by Change in Plasma C-peptide
Description
Change in plasma c-peptide level
Time Frame
Day -1 to 17

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. 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. 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. 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. 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). Subjects who, in the opinion of the Investigator, should not participate in in this study based on other reasons.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Youngah Kim
Phone
82-31-8002-2558
Email
yakim116@glaceum.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kyung Sang Yu, MD, PhD
Organizational Affiliation
Seoul National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kyung Sang Yu, MD, PhD
First Name & Middle Initial & Last Name & Degree
Kyung Sang Yu, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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