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About
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.
Full description
This Phase 2a, multinational, randomized, double-blind, placebo-controlled, dose-finding clinical trial is designed to evaluate the efficacy, safety, and pharmacokinetics of KDS2010, a novel, reversible monoamine oxidase-B (MAO-B) inhibitor, in overweight or obese adult patients. The clinical trial is conducted at selected sites in Korea and the United States.
The study consists of two stages and will enroll approximately 75 subjects. In Stage 1, 9 subjects will be randomized in a 2:1 ratio (KDS2010 120 mg: placebo) to evaluate initial safety and tolerability. Upon completion of the week 13 visit for the last subject in Stage 1, a Safety Review Committee (SRC) will assess cumulative safety data to determine the appropriateness of dose escalation and progression to Stage 2.
If cleared by the SRC, Stage 2 will proceed with 66 subjects randomized equally across three arms in a 1:1:1 ratio: KDS2010 120 mg, KDS2010 180 mg, and placebo. Randomization will consider stratification by region (Korea/USA). All subjects will undergo a 2-week run-in period prior to randomization to confirm eligibility based on adherence to lifestyle modification (documented reduction of ≥500 kcal/day and ≥150 minutes of physical activity per week for ≥50% of the run-in period).
The treatment period consists of 12 weeks of once-daily oral administration of the investigational product (IP), followed by a 1-week post-treatment safety follow-up (week 13). During treatment, subjects will visit the site at Weeks 4, 8, and 12, with a telephone visit at Week 2. Safety follow-up will be conducted by phone at Week 13.
The primary efficacy endpoint is the percentage change in body weight from baseline to Week 12. Secondary efficacy endpoints include the proportion of subjects achieving ≥5%, ≥10%, ≥15%, and ≥20% weight loss and changes in waist circumference, BMI, blood pressure (SBP/DBP), quality of life (IWQOL-Lite-CT), body composition (DEXA), lipid profile, glycemic parameters (HbA1c, fasting glucose, HOMA-IR), and liver steatosis. Exploratory endpoints assess the proportion of subjects with ≥25% weight loss, as well as changes in MAO-B specific activity and adiponectin levels.
Safety will be evaluated through monitoring of adverse events (AEs), laboratory tests, vital signs, ECGs, and psychological assessments, including the Columbia-Suicide Severity Rating Scale (C-SSRS) and Patient Health Questionnaire-9 (PHQ-9). Pharmacokinetic parameters (AUCtau, Cmax,ss, Cmin,ss, Cav,ss, Tmax,ss, t1/2, PTF, etc.) will be measured to assess systemic exposure to KDS2010.
Subjects must be adults (≥18 years), have a BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity, and demonstrate compliance with lifestyle modification during the run-in. Major exclusion criteria include recent significant weight change (≥5% within 12 weeks), use of anti-obesity drugs or MAO inhibitors, type 1 or 2 diabetes, bariatric surgery, uncontrolled hypertension, hepatic or renal dysfunction, significant psychiatric disorders, or suicidal ideation/attempts.
The total study duration is expected to be approximately 24 months from the IRB/IEC approval, with individual subject participation lasting up to 17 weeks. This trial aims to evaluate the safety, efficacy, and pharmacokinetic of KDS2010 for future development in the treatment of obesity.
Enrollment
Sex
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Volunteers
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
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,
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),
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.
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
Primary purpose
Allocation
Interventional model
Masking
75 participants in 5 patient groups, including a placebo group
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Central trial contact
Sujeong Shin, Professor; Jaeheon Kang, Professor
Data sourced from clinicaltrials.gov
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