Obesity
Conditions
Brief summary
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.
Interventions
DRUGHSG4112
Once-daily, 14-day multiple oral administration
DRUGPlacebo
Once-daily, 14-day multiple oral administration
Sponsors
Kyungpook National University Hospital
Seoul National University Hospital
Glaceum
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
\<Part 1\> Inclusion Criteria: 1. Able to comprehend and willing to sign an informed consent form approved by the IRB before screening. 2. Females between 19 and 50 years of age at screening. 3. Body mass index (BMI) between 18.0 and 24.9. * BMI (kg/m2) = 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 evaluations at screening, or subjects who are deemed acceptable by the Investigator regardless of the test results. 5. Not pregnant or lactating, with a regular menstrual cycle (i.e., 28±7 days).
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., Chrons disease, ulcer) or surgeries - not including appendectomy, hemorrhoidectomy, or herniotomy - which may affect the pharmacokinetic or pharmacodynamic evaluation of the investigational product. 3. Significant history or clinical manifestation of hypersensitivity to any drug compound (e.g., licorice, aspirin, antibiotics). 4. One or more of the following laboratory test results at screening: * ALT \> 60 IU/L * Glucose (fasting) \> 100 mg/dL or \< 70 mg/dL 5. Systolic blood pressure of \< 90 mmHg or \> 150 mmHg, or diastolic blood pressure of \< 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. 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. 8. 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). 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. Smoker. However, participation is acceptable if the subject has quit smoking at least 3 months prior to dosing. 11. Alcohol consumption of \> 21 units/week (1 unit = 10 g of pure alcohol) or unable to abstain from consuming alcohol during the study period. 12. Ingestion of grapefruit-containing foods or beverages 24 hours prior to dosing until discharge, or unable to abstain from ingesting such foods or beverages during the same period. 13. Unable to abstain from caffeine-containing foods or beverages (e.g., coffee, tea (e.g., black tea, green tea), soft drinks, coffee milk, energy drinks, sports drinks) during the admission period. 14. One or more of the following contraception- or pregnancy-related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Assessment by Number of Patients with Change in Physical Examination | Day -1, 1 to 14, 17, and post-study visit | Number of participants with clinically significant change in physical examination |
| Pharmacokinetic Assessment by Half-Life of HSG4112 | Hour 0 to 192 | Half-life of HSG4112 (T1/2) |
| Safety and Tolerability Assessment by Number of Participants with Change in Vital Signs | Day 1, 14, and post-study visit | 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 |
| Safety and Tolerability Assessment by Number of Participants with Change in 12-Lead Electrocardiogram | Day -1, 11, and post-study visit | Number of participants with clinically significant change in 12-lead electrocardiogram |
| Safety and Tolerability Assessment by Number of Participants with Change in Laboratory Test | Day -1, 8, 13, 15, 17, and post-study visit | Number of participants with clinically significant change in laboratory test assessed through hematology, blood biochemistry, urinalysis, and blood coagulation test |
| Safety and Tolerability Assessment by Pregnancy Test | Day -1, 11, and post-study visit | Monitoring the pregnancy status of participants through urine pregnancy test by measuring the level of human chorionic gonadotropin |
| Pharmacokinetic Assessment by Oral Clearance of HSG4112 | Hour 0 to 192 | Oral clearance of HSG4112 (CLss/F) |
| Pharmacokinetic Assessment by Volume of Distribution of HSG4112 | Hour 0 to 192 | Volume of distribution of HSG4112 (Vd/F) |
| Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HSG4112 Over Dosing Interval | Hour 0 to 24 | Area under the plasma concentration-time curve of HSG4112 over dosing interval (AUCtau,ss) |
| Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HSG4112 from Time Zero to the Last Measurable Point | Hour 0 to 192 | Area under the plasma concentration-time curve from time zero to the last measurable point (AUClast) |
| Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of HSG4112 from Time Zero to Infinity | Hour 0 to 192 | Area under the plasma concentration-time curve from time zero to infinity (AUCinf) |
| Pharmacokinetic Assessment by Maximum and Minimum Plasma Concentration of HSG4112 | Hour 0 to 192 | Maximum and minimum plasma concentration of HSG4112 (Cmax,ss; Cmin,ss) |
| Pharmacokinetic Assessment by Time to Maximum Observed Plasma Concentration of HSG4112 | Hour 0 to 192 | Time to maximum observed plasma concentration of HSG4112 (Tmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Assessment by Change of Body Weight in Obese Subjects | Day 1 to 17, 18, 20, and 22 | Assessment of the weight loss effect of HSG4112 by change of observed body weight compared to baseline (kg) |
| Pharmacodynamic Assessment by Change of Waist Circumference | Day -1, 8, 15, and 22 | Assessment of the weight loss effect of HSG4112 by change of observed waist circumference compared to baseline (cm) |
| Pharmacodynamic Assessment by Change of Biomarkers | Day 1 and 14 pre-dose | 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 |
| Pharmacodynamic Assessment by Change of Fat Mass and Body Fat Percentage | Day 1, 8, 15, and 22 | Assessment of the weight loss effect of HSG4112 by change of fat mass (kg) and body fat percentage (%) compared to baseline |
| Pharmacodynamic Assessment by Change of Body Weight in Healthy Subjects | Day -1, 8, 15, and 22 | Assessment of the weight loss effect of HSG4112 by change of observed body weight compared to baseline (kg) |
Countries
South Korea
Outcome results
None listed