A Study to Investigate the Safety, Tolerability and Pharmacokinetics of TB-840 in Healthy Subjects

A Dose Block-randomized, Double-blind, Placebo Controlled, Single-/Multiple-dosing, Dose-escalation Phase 1 Clinical Trial to Investigate the Safety, Tolerability, Pharmacokinetic Characteristics of TB-840 (NASH Treatment Candidate) After Oral Administration in Healthy Subjects

TB-840(Agonist of RORα) is a candidate for NASH treatment that activates RORα(Retinoid-related orphan receptor) and its target validation for RORα and potential as a NASH treatment. This study is a dose block-randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study. For each dose group, 6 subjects will be randomly assigned to the test group (TB-840) and 2 subjects will be randomly assigned to the control group (placebo). Adverse event (AE) monitoring, physical examination, vital signs, ECG, clinical laboratory test will be done for safety and tolerability assessment, and blood and urine samples will be collected for Pharmacokinetic (PK) assessment.

Inclusion Criteria:

• Healthy adults aged ≥ 19 and ≤ 45 years at the time of screening visit
• BMI of ≥ 18.0 and ≤ 27.0 kg/m2 at the time of screening visit
• Clinically confirmed as healthy based on the medical history, physical examination, vital signs, electrocardiography (ECG), and proper laboratory tests (Subjects with values out of the normal range may participate in the study if they are deemed clinically insignificant by the investigator.)
• Agree to use medically acceptable methods of contraception by participant, his/her spouse, or partner and not to donate sperm or oocyte from the date of the first dose of the investigational product (IP) until 90 days after the last dose of the IP
• Examples of medically acceptable methods of contraception
• Females (females who use oral hormonal contraceptives and subcutaneous hormonal contraceptive implants may be excluded from the study)
• Use of an intrauterine device with a proven pregnancy failure rate
• Use of barrier method with spermicide
• Surgical sterilization (salpingectomy/tubal ligation, hysterectomy, etc.)
• Males
• Use of barrier method with spermicide
• Surgical sterilization (vasectomy, vasoligation, etc.)
• Voluntarily decided to participate in the study and provided written consent to comply with the protocol

Exclusion Criteria:

• Current or history of a clinically significant hepatic, renal, gastrointestinal, respiratory, musculoskeletal, endocrine, neuropsychiatric, hemato-oncological, or cardiovascular disease
• History of gastrointestinal diseases (e.g., Crohn's disease, ulcer, etc.) or surgery (excluding simple appendectomy or hernia repair) that may affect the absorption of the investigational products
• History of clinically significant hypersensitivity to drugs containing RORα agonist or other ingredients of the same class, or other drugs (aspirin and non-steroidal anti-inflammatory drugs, antibiotics, etc.)
• History of drug abuse or positive result from urine drug screening of drugs with concerns of drug abuse
• Subjects with any of the following results at the time of screening visit:
• Systolic blood pressure: < 90 mmHg or > 140 mmHg
• Diastolic blood pressure: < 50 mmHg or > 90 mmHg
• Heart rate: < 50 bpm or > 100 bpm
• AST: > x 1.5 ULN
• ALT: > x 1.5 ULN
• ALP: > x 1.5 ULN
• T.bil: > x 1.5 ULN
• γ-GT： > x 1.5 ULN
• Serum creatinine: > x 1.5 ULN
• Participated in another bioequivalence study or clinical study and have been exposed to an investigational product within 6 months prior to the date of the first dose of this study
• Donated whole blood within 2 months or blood components within 1 month, or received blood transfusion within 1 month prior to the date of the first dose of this study
• Use of drug-metabolizing enzyme inducer or inhibitor such as barbiturates within 1 month prior to the date of the first dose of this study
• Consumption of caffeine- or grapefruit-containing foods or beverages within 3 days prior to the date of the first dose of this study
• Use of any prescription drugs or herbal medicines within 1 month, or any over-the-counter (OTC) drugs within 1 week prior to the date of the first dose of this study (Subjects may participate in the study if such use is judged not to significantly affect the assessment of safety and pharmacokinetics by the investigator.)
• Excessive intake of caffeine, excessive intake of alcohol, or heavy smoking (caffeine > 5 units/day, alcohol > 21 units/week [1 unit = 10 mL of pure alcohol], smoking > 10 cigarettes/day)
• Unable to consume meals provided by the study site
• Prior participation in this study
• Positive result in serology tests (hepatitis B tests, human immunodeficiency virus [HIV] tests, hepatitis C tests, or syphilis tests [RPR])
• Determined inappropriate for the study by the investigator