Overview

This is a randomized, double-blind, placebo-controlled, dose-escalation, Phase 2a study designed to evaluate the safety and efficacy of KDS2010 in overweight or obese patients. Based on preliminary efficacy observed in the Phase 1 study, a multinational clinical trial is being conducted in both Korea and the United States. After a minimum 2-week run-in period, subjects who meet the inclusion and exclusion criteria will be randomized into each dose group at a 2:1 ratio in Stage 1 and in a 1:1:1 ratio in Stage 2, considering stratification by region (Korea/USA).

Subjects will receive the investigational drug for 12 weeks following randomization. Approximately 75 subjects will be enrolled, with 6 subjects in the treatment group and 3 subjects in the control group in Stage 1, and 22 subjects per group in Stage 2.

The primary objectives are to assess the efficacy and safety of KDS2010 in overweight or obese patients. Exploratory objectives include evaluating the proportion of subjects achieving a weight reduction of more than 25% from baseline at Week 12 and assessing changes in MAO-B specific activity and adiponectin levels.

Based on nonclinical and Phase 1 clinical data, KDS2010 will be administered orally once daily at doses of 120 mg and 180 mg throughout the study.

Eligibility

Inclusion Criteria:

• Adult males and females aged 18 years or older (or the legal age of adulthood in the respective country) as of the date of written consent
• Subjects with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, cardiovascular disease, obstructive sleep apnea) at screening and baseline
  • Hypertension: under treatment or have Systolic Blood Pressure (SBP) ≥130 mmHg or Diastolic Blood Pressure (DBP) ≥80 mmHg
  • Dyslipidemia: under treatment or LDL > 160 mg/dL or TG > 200 mg/dL or HDL < 40 mg/dL
  • Cardiovascular diseases (e.g., ischemic cardiovascular disease, NYHA Class I to III heart failure, Peripheral vascular disease (PVD), Abdominal aortic aneurysm (AAA), etc.)
  • Obstructive sleep apnoea
• Subjects who have documented a 500 kcal reduction/day in calorie intake and ≥150

  minutes of physical activity/week for ≥50% of the time during the run-in period

• Subjects who have voluntarily provided written consent to participate after being informed about this clinical trial

Exclusion Criteria:

• Subjects with a weight change of 5% or more within 12 weeks before screening
• Subjects with less than 80% or more than 120% compliance during the Run-in period
• Subjects with obesity due to secondary causes (neurological disorders, endocrine disorders, genetic disorders, congenital disorders, etc.)
• Subjects with following medical history,
  • Type 1 or Type 2 diabetes
  • History of bariatric/metabolic surgery (e.g., adjustable gastric banding, intragastric balloon insertion, sleeve gastrectomy, Roux-en-Y gastric bypass, biliopancreatic diversion, duodenal switch) or planning to undergo such surgery during the study period
  • Heart failure classified as NYHA class IV
  • Subjects with a medical history of malignant tumors within 5 years prior to screening (however, subjects with successfully treated basal cell carcinoma, squamous cell carcinoma of the skin, thyroid cancer, or other carcinoma in situ, with no recurrence for more than 3 years, may be enrolled at the investigator's discretion)
  • Subjects with a medical history of hypersensitivity to MAO inhibitors
  • Subjects with a medical history of cerebrovascular disease (e.g., transient ischemic attack, stroke) within 12 weeks prior to baseline, or those hospitalized for unstable angina or congestive heart failure
  • Subjects with a history of depressive disorders or psychiatric disorders (e.g., schizophrenia, bipolar disorder, anxiety disorder) within 2 years prior to screening
• Subjects with a history of the following drug administration,

  -- Anti-obesity agents or weight-loss medications (including dietary supplements and herbal medicine) within 12 weeks before screening

  • Corticosteroids administered for 2 consecutive weeks or more within 12 weeks before screening (however, topical preparations, including inhalants, are allowed)
  • Treatment for hyperthyroidism or hypothyroidism at the time of screening (subjects on a stable dose and regimen for at least 12 weeks may be enrolled at the investigator's discretion)
  • MAO inhibitors within 2 weeks before baseline
  • Opioid medications (e.g., pethidine, Tramadol, Tapentadol) within 2 weeks before baseline
  • Serotonergic drugs within 2 weeks before baseline,
    • Selective Serotonin Reuptake Inhibitors (SSRI), ② Serotonin-Norepinephrine Reuptake Inhibitors (SNRI),
      • Tricyclic or Tetracyclic antidepressant, ④ Triazolopyridine antidepressant, ⑤ Selective serotonin (5-HT1) agonists (Sumatriptan, etc.), (However, amitriptyline ≤50 mg/day, trazodone ≤100 mg/day, citalopram ≤20 mg/day, sertraline ≤100 mg/day, paroxetine ≤30 mg/day are allowed; long half-life serotonergic drugs (e.g., fluoxetine) require at least a 5-week wash out period before enrollment),
  • Lithium, Bupropion, Lamotrigine, Ritonavir, Cyclobenzaprine, or St. John's wort

    within 2 weeks before baseline

  • Hypertension crisis-inducing drugs (e.g., oxymetazoline, phentermine, phenylephrine) within 2 weeks before baseline
  • Sympathomimetic agents (e.g., ephedrine, methylphenidate, amphetamine, methamphetamine, lisdexamfetamine) at the time of screening
  • Dextromethorphan at the time of screening
• Subjects who meet following criteria based on the tests conducted at Screening
  • Glycated hemoglobin (HbA1c) ≥6.5%
  • Hepatic impairment (Child-pugh class C)
  • AST or ALT > 2.5 X ULN
  • Total bilirubin >1.5 X ULN (however, >3.0 mg/dL is acceptable in cases of Gilbert syndrome)
  • Severe renal impairment (eGFR <30 mL/min/1.73 m² calculated using the MDRD formula*),
    • eGFR = 175 X (Serum creatinine)-1.154 X (Age)-0.203 X (0.742 (for females)) X (1.212 (for African Americans))
  • TSH >6.0 mIU/L or <0.4 mIU/L,
• Subjects with a lifetime history of suicide attempts
• Subjects with a PHQ-9 score of 10 or higher at screening
• Subjects who answer affirmatively to item 4 or 5 on the C-SSRS at screening
• Pregnant or breastfeeding women
• Females of childbearing potential and males who do not agree to use adequate contraception# until at least 2 weeks after the last dose of the IP or who plan to conceive during the study period,
  • Adequate contraception is defined as double contraception using both barrier methods (male condom or female condom) and one of the contraceptive methods ①-③.
    • Hormonal contraceptive (oral, injectable, implantable, etc.), ② Implantation of Intrauterine device (IUD) or intrauterine system (IUS), ③ Sterilization procedures or surgeries (bilateral tubal ligation, hysterectomy, vasectomy), ④ Complete abstinence: absolute abstinence is accepted if, in the investigator's judgment, the subject's age, occupation, lifestyle, or sexual orientation ensure compliance with contraception. However, periodic abstinence (calendar method, ovulation method, symptothermal method, etc.) withdrawal, and coitus interruptus are not considered adequate contraceptive methods.,
• Subjects who have participated in another clinical trial and received an

  investigational drug or device within 4 weeks prior to screening

• Other reasons (such as a medical history of alcohol or substance abuse) that the investigator deems the subject unsuitable for participation in this clinical trial