A Study to Investigate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics, and Food Effect of HSG4112

NCT04732988 | Completed Phase 1

• 1 other identifier: HSG4112-P1-01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

1. 1.Study Objective: The objective of this phase 1 clinical trial is to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic characteristics and food effect of HSG4112 after oral administration in healthy male subjects.
2. 2.Study Design and Plan: This study is a dose-block randomized, double-blind, placebo-controlled, single and multiple dosing, dose-escalation phase 1 clinical trial. A unique randomization number will be assigned to each subject deemed eligible to participate in the study based on the inclusion/exclusion criteria. Each subject will be randomized to one of the six groups for the single ascending dose (SAD) study or one of the three groups for the multiple ascending dose (MAD) study. Each dose group will consist of ten subjects, and among the ten subjects, eight subjects will be randomized to receive HSG4112 and two subjects will be randomized to receive placebo. The subjects will be studied in a double-blind manner and will receive the investigational product (i.e., HSG4112 or placebo) via once-daily oral administration. The dosing duration for the MAD study is 14 days. When escalating the dose, the Investigator will review all of the available safety data from the preceding dose in a blinded manner to ensure if it is safe to escalate the dose. In order to evaluate safety and tolerability, assessments, such as vital signs, 12-lead electrocardiogram, laboratory test, semen analysis (MAD study only), physical examination, and adverse event monitoring will be performed. Blood samples will be collected to evaluate the pharmacokinetic/pharmacodynamic characteristics of HSG4112.

Conditions

Obesity

Outcome Measures

Primary Outcomes (19)

• Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HSG4112 Over Dosing Interval

  Area under the plasma concentration-time curve of HSG4112 over dosing interval (AUCtau)

  Hour 0 to 24

• Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HSG4112 from Time Zero to the Last Measurable Point

  Area under the plasma concentration-time curve from time zero to the last measurable point (AUClast)

  Hour 0 to 192

• Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HSG4112 from Time Zero to Infinity

  Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

  Hour 0 to 192

• Pharmacokinetic Assessment by Maximum Plasma Concentration of HSG4112

  Maximum plasma concentration of HSG4112 (Cmax)

  Hour 0 to 192

• Pharmacokinetic Assessment by Time to Maximum Observed Plasma Concentration of HSG4112

  Time to maximum observed plasma concentration of HSG4112 (Tmax)

  Hour 0 to 192

• Pharmacokinetic Assessment by Half-Life of HSG4112

  Half-life of HSG4112 (T1/2)

  Hour 0 to 192

• Pharmacokinetic Assessment by Oral Clearance of HSG4112

  Oral clearance of HSG4112 (CL/F)

  Hour 0 to 192

• Pharmacokinetic Assessment by Volume of Distribution of HSG4112

  Volume of distribution of HSG4112 (Vd/F)

  Hour 0 to 192

• Safety and Tolerability Assessment by Adverse Event Monitoring

  Number of participants with observed adverse events

  Up to 12 weeks from day of last dosing

• 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 (mmHg) measured with blood pressure monitor, heart rate (beats per minute) measured with pulse oximeter, and body temperature (degrees Celcius) measured with thermometer

  Up to 3 weeks from day of last dosing

• 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

  Up to 3 weeks from day of last dosing

• 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, and blood coagulation test

  Up to 3 weeks from day of last dosing

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

  Number of participants with clinically significant change in physical examination

  Up to 3 weeks from day of last dosing

• Safety and Tolerability Assessment by Number of Patients with Change in Semen Volume

  Pre-to-post examination of semen volume (milliliters) by semen analysis to assess the safety and tolerability of HSG4112

  Up to 12 weeks from day of last dosing

• Safety and Tolerability Assessment by Number of Patients with Change in Semen pH

  Pre-to-post examination of semen white blood cells (10\^3 per microliter) by semen analysis to assess the safety and tolerability of HSG4112

  Up to 12 weeks from day of last dosing

• Safety and Tolerability Assessment by Number of Patients with Change in Semen White Blood Cells

  Pre-to-post examination of semen white blood cells (10\^3 per microliter) by semen analysis to assess the safety and tolerability of HSG4112

  Up to 12 weeks from day of last dosing

• Safety and Tolerability Assessment by Number of Patients with Change in Sperm Count

  Pre-to-post examination of sperm count (10\^6 per milliliter) by semen analysis to assess the safety and tolerability of HSG4112

  Up to 12 weeks from day of last dosing

• Safety and Tolerability Assessment by Number of Patients with Change in Sperm Motility

  Pre-to-post examination of sperm motility (percent of sperm with normal motility) by semen analysis to assess the safety and tolerability of HSG4112

  Up to 12 weeks from day of last dosing

• Safety and Tolerability Assessment by Number of Patients with Change in Sperm Morphology

  Pre-to-post examination of sperm morphology (percent of normal sperm) by semen analysis to assess the safety and tolerability of HSG4112

  Up to 12 weeks from day of last dosing

Secondary Outcomes (1)

• Pharmacodynamic Assessment by Change of Biomarkers

  Day 1 and 14 pre-dose

Study Arms (17)

HSG4112 30 mg Single Dose

EXPERIMENTAL

Single oral dosing of HSG4112 30 mg

Drug: HSG4112

Placebo 30 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of Placebo 30 mg

Drug: Placebo

HSG4112 60 mg Single Dose

EXPERIMENTAL

Single oral dosing of HSG4112 60 mg

Drug: HSG4112

Placebo 60 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of Placebo 60 mg

Drug: Placebo

HSG4112 120 mg Single Dose

EXPERIMENTAL

Single oral dosing of HSG4112 120 mg

Drug: HSG4112

Placebo 120 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of Placebo 120 mg

Drug: Placebo

HSG4112 240 mg Single Dose (Fasted)

EXPERIMENTAL

Single oral dosing of HSG4112 240 mg under fasted conditions

Drug: HSG4112

HSG4112 240 mg Single Dose (Fed)

EXPERIMENTAL

Single oral dosing of HSG4112 240 mg under fed conditions

Drug: HSG4112

Placebo 240 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of Placebo 240 mg

Drug: Placebo

HSG4112 480 mg Single Dose

EXPERIMENTAL

Single oral dosing of HSG4112 480 mg

Drug: HSG4112

Placebo 480 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of Placebo 480 mg

Drug: Placebo

HSG4112 720 mg Single Dose

EXPERIMENTAL

Single oral dosing of HSG4112 720 mg

Drug: HSG4112

Placebo 720 mg Single Dose

PLACEBO COMPARATOR

Single oral dosing of Placebo 720 mg

Drug: Placebo

HSG4112 240 mg Multiple Dose

EXPERIMENTAL

Once-daily multiple oral dosing of HSG4112 240 mg for 14 days

Drug: HSG4112

Placebo 240 mg Multiple Dose

PLACEBO COMPARATOR

Once-daily multiple oral dosing of Placebo 240 mg for 14 days

Drug: Placebo

HSG4112 480 mg Multiple Dose

EXPERIMENTAL

Once-daily multiple oral dosing of HSG4112 480 mg for 14 days

Drug: HSG4112

Placebo 480 mg Multiple Dose

PLACEBO COMPARATOR

Once-daily multiple oral dosing of Placebo 480 mg for 14 days

Drug: Placebo

Interventions

HSG4112 DRUG

Once-daily oral administration

Also known as: 2-(8,8 dimethyl 2,3,4,8,9,10 hexahydropyrano[2,3 f]chromen 3 yl) 5 ethoxyphenol

HSG4112 120 mg Single Dose; HSG4112 240 mg Multiple Dose; HSG4112 240 mg Single Dose (Fasted); HSG4112 240 mg Single Dose (Fed); HSG4112 30 mg Single Dose; HSG4112 480 mg Multiple Dose; HSG4112 480 mg Single Dose; HSG4112 60 mg Single Dose; HSG4112 720 mg Single Dose

Placebo DRUG

Once-daily oral administration

Placebo 120 mg Single Dose; Placebo 240 mg Multiple Dose; Placebo 240 mg Single Dose; Placebo 30 mg Single Dose; Placebo 480 mg Multiple Dose; Placebo 480 mg Single Dose; Placebo 60 mg Single Dose; Placebo 720 mg Single Dose

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: male
• 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.
• Males between 19 and 50 years of age at screening.
• Body mass index (BMI) between 18 and 24.9.
• ☞ BMI (kg/m2) = 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 test 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., Chrons disease, ulcer) or surgeries - not including appendectomy, hemorrhoidectomy, or herniotomy - which may affect the pharmacokinetic or pharmacodynamic evaluation of the investigational product.
• Significant history or clinical manifestation of hypersensitivity to any drug compound (e.g., licorice, aspirin, antibiotics).
• One of more of the following laboratory test results at screening:
• ALT (SGPT) \> 60 IU/L
• Glucose (fasting) \> 110 mg/dL or \< 70 mg/dL
• Testosterone \<2.49 ng/mL or \> 8.36 ng/mL
• Systolic blood pressure of \< 90 mmHg or \> 150 mmHg, or diastolic blood pressure of \< 60 mmHg 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.
• Use 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 involving administration of an investigational drug, including any study investigating HSG4112, within 6 months prior to dosing (i.e., within 6 months of the last dose from the previous study).
• 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, or receipt of blood products within 1 month prior to dosing.
• Alcohol consumption of \> 20 units/week (1 unit = 10 g of pure alcohol) or unable to abstain from consuming alcohol during the study period.
• Smoked within 90 days prior to dosing. However, participation is acceptable if the subject has quit smoking at least 90 days prior to dosing.
• Smoker. However, participation is acceptable if the subject has quit smoking at least 3 months prior to dosing.

Sponsors & Collaborators

• Glaceum: lead
• Seoul National University Hospital: collaborator
• Kyungpook National University Hospital: collaborator

Study Sites (2)

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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: January 19, 2021
• First Posted: February 1, 2021
• Study Start: August 23, 2018
• Primary Completion: May 24, 2021
• Study Completion: May 24, 2021
• Last Updated: November 1, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)