1. Study Objective \<Part 1\> To evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of HSG4112 after multiple oral administration in healthy female subjects. \<Part 2\> To evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of HSG4112 after multiple oral administration in obese subjects. 2. Background The previous phase 1 clinical trials investigating HSG4112 only included healthy male subjects, and food effect was observed in theses studies - the plasma exposure to HSG4112 following administration under fed conditions was approximately 2.5 times higher compared to the exposure following administration under fasted conditions. Therefore, this study is designed to evaluate the safety of HSG4112 in healthy female subjects and obese subjects following the administration of HSG4112 under fed conditions. 3. Study Design and Plan \<Part 1\> This study is a dose block-randomized, double-blind, placebo-controlled, multiple dosing, phase 1 clinical study. 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 two dose groups. In each dose group, 8 subjects will be randomized to receive HSG4112 and 2 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 for 14 consecutive days. After the Post-Study Visit of the last volunteer in the 480 mg dose group, the Investigator will review all the available safety data in a blinded manner to ensure if it is safe to proceed with the 720 mg dose group. In order to evaluate safety and tolerability, assessments, such as vital signs, 12-lead ECG, laboratory test, pregnancy test, physical examination, and adverse event monitoring will be performed. Blood samples will be collected to evaluate the pharcokinetic/pharmacodynamic characteristics of HSG4112. \<Part 2\> This study is a dose block-randomized, double-blind, placebo-controlled, multiple dosing, phase 1 clinical study. 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 two dose groups. In each dose group, 8 subjects will be randomized to receive HSG4112 and 2 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 for 14 consecutive days. In order to evaluate safety and tolerability, assessments, such as vital signs, 12-lead ECG, laboratory test, pregnancy test, physical examination, and adverse event monitoring will be performed. Blood samples will be collected to evaluate the pharcokinetic/pharmacodynamic characteristics of HSG4112.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
Kyungpook National University Hospital
Daegu, South Korea
Seoul National University Hospital
Seoul, South Korea
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,ss)
Time frame: 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)
Time frame: 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)
Time frame: Hour 0 to 192
Pharmacokinetic Assessment by Maximum and Minimum Plasma Concentration of HSG4112
Maximum and minimum plasma concentration of HSG4112 (Cmax,ss; Cmin,ss)
Time frame: Hour 0 to 192
Pharmacokinetic Assessment by Time to Maximum Observed Plasma Concentration of HSG4112
Time to maximum observed plasma concentration of HSG4112 (Tmax)
Time frame: Hour 0 to 192
Pharmacokinetic Assessment by Half-Life of HSG4112
Half-life of HSG4112 (T1/2)
Time frame: Hour 0 to 192
Pharmacokinetic Assessment by Oral Clearance of HSG4112
Oral clearance of HSG4112 (CLss/F)
Time frame: Hour 0 to 192
Pharmacokinetic Assessment by Volume of Distribution of HSG4112
Volume of distribution of HSG4112 (Vd/F)
Time frame: Hour 0 to 192
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
Time frame: Day 1, 14, and post-study visit
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
Time frame: Day -1, 11, and post-study visit
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
Time frame: Day -1, 8, 13, 15, 17, and post-study visit
Safety and Tolerability Assessment by Pregnancy Test
Monitoring the pregnancy status of participants through urine pregnancy test by measuring the level of human chorionic gonadotropin
Time frame: Day -1, 11, and post-study visit
Safety and Tolerability Assessment by Number of Patients with Change in Physical Examination
Number of participants with clinically significant change in physical examination
Time frame: Day -1, 1 to 14, 17, and post-study visit
Pharmacodynamic Assessment by Change of Body Weight in Healthy Subjects
Assessment of the weight loss effect of HSG4112 by change of observed body weight compared to baseline (kg)
Time frame: Day -1, 8, 15, and 22
Pharmacodynamic Assessment by Change of Body Weight in Obese Subjects
Assessment of the weight loss effect of HSG4112 by change of observed body weight compared to baseline (kg)
Time frame: Day 1 to 17, 18, 20, and 22
Pharmacodynamic Assessment by Change of Waist Circumference
Assessment of the weight loss effect of HSG4112 by change of observed waist circumference compared to baseline (cm)
Time frame: Day -1, 8, 15, and 22
Pharmacodynamic Assessment by Change of Biomarkers
Assessment of the weight loss effect of HSG4112 by measurement of biomarkers including leptin, adiponectin, insulin, C-peptide (connecting peptide), IL6 (interleukin 6), TNF-alpha (tumor necrosis factor alpha), and CCL2 (C-C motif ligand 2) from baseline to day of last dosing
Time frame: Day 1 and 14 pre-dose
Pharmacodynamic Assessment by Change of Fat Mass and Body Fat Percentage
Assessment of the weight loss effect of HSG4112 by change of fat mass (kg) and body fat percentage (%) compared to baseline
Time frame: Day 1, 8, 15, and 22
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