A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose, Phase 1 Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability After Oral Administration of AJH-2947 in Healthy Korean or Caucasian Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Part A (SAD): Urine concentrations of AJH-2947
研究概览
简要总结
The purpose of this randomized, double-blind, placebo-controlled Phase 1 study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of AJH-2947 in healthy Korean or Caucasian adult male participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 19 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy Korean or Caucasian adult males aged 19 to 55 years at the time of written informed consent. Caucasian participants were defined as individuals born in Europe who had resided outside Europe for less than 10 years and whose parents and grandparents were all of European descent.
- •Body weight between 50.0 kg and 90.0 kg and body mass index (BMI) from 18.5 kg/m² to less than 30.0 kg/m².
- •Willingness to remain in the Clinical Trial Center (CTC) until discharge and to use sunscreen until the end of the study, including the post-study visit (PSV).
- •Ability to understand the study after receiving a detailed explanation, voluntary agreement to participate, and provision of written informed consent before any screening examination.
- •Considered suitable for participation by the investigator based on medical history, vital signs, 12-lead electrocardiogram (ECG), physical examination, and clinical laboratory test results obtained during screening.
排除标准
- •Clinically significant disease or a history of disease involving the liver, kidney, nervous system, immune system, respiratory system, digestive system, endocrine system, hematologic system, cardiovascular system, urinary system, psychiatric system, or other clinically relevant body system.
- •For the multiple-dose trial, skin lesions or tattoos on both forearms, or hypersensitivity or allergic reactions to capsaicin cream that could affect pharmacodynamic evaluation.
- •Gastrointestinal disease, including gastrointestinal ulcer, gastritis, gastric spasm, gastroesophageal reflux disease, or Crohn's disease, or a history of surgery that could affect the safety or pharmacokinetic evaluation of the investigational product, except for simple appendectomy or hernia repair.
- •History of hypersensitivity to the active ingredient or other components of the investigational product, or to drugs of the same class.
- •Positive screening result for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis (RPR), or human immunodeficiency virus (HIV).
- •Supine systolic blood pressure below 80 mmHg or at least 140 mmHg, or diastolic blood pressure below 45 mmHg or at least 90 mmHg, measured after at least 3 minutes of rest.
- •History of drug abuse or a positive urine drug screening result.
- •Use of prescription medication or traditional herbal medicine within 2 weeks before the scheduled first dose, or use of over-the-counter medication, health-functional food, or vitamin supplements within 1 week before the scheduled first dose, or anticipated use of any such product during the study.
- •Participation in another clinical trial, including a bioequivalence study, within 6 months before the scheduled first dose.
- •Donation of whole blood within 2 months, donation of blood components within 1 month, or receipt of a blood transfusion within 1 month before the scheduled first dose.
- •Excessive caffeine consumption of more than 5 units per day or inability to abstain from caffeine or caffeine-containing foods and beverages from 3 days before the expected first dose until the end of the study, including the PSV.
- •Persistent alcohol consumption of more than 21 units per week, with 1 unit defined as 10 g of pure alcohol, or inability to abstain from alcohol from 3 days before the expected first dose until the end of the study, including the PSV.
- •Smoking more than 10 cigarettes per day within the 3 months before the scheduled first dose or inability to stop smoking from screening until the end of the study, including the PSV.
- •Inability to refrain from consuming grapefruit-containing foods from 3 days before the expected first dose until the end of the study, including the PSV.
- •Planning a pregnancy during the study or within 90 days after the last administration of the investigational product, or unwillingness to use at least one medically acceptable contraceptive method. Acceptable methods included use of an intrauterine device with a proven failure rate by the participant's spouse or partner; concurrent use of barrier contraception and oral contraceptive pills; or surgical sterilization of the participant or partner, including vasectomy, salpingectomy, tubal ligation, or hysterectomy.
- •Considered unsuitable for participation by the investigator for any other reason, including clinical laboratory test results.
研究组 & 干预措施
Part A: Single Ascending Dose (SAD)
Healthy Korean or Caucasian adult male participants received a single oral dose of AJH-2947 or placebo across seven dose cohorts under fasted or fed conditions.
干预措施: AJH-2947 tablets or placebo (Drug)
Part B: Multiple Ascending Dose (MAD)
Healthy Korean or Caucasian adult male participants received AJH-2947 or placebo orally once daily for 7 days across three dose cohorts under fed conditions.
干预措施: AJH-2947 tablets or placebo (Drug)
结局指标
主要结局
Part A (SAD): Urine concentrations of AJH-2947
时间窗: Day 1 to Day 4
To characterize the urine concentration of AJH-2947 after single oral dosing in healthy Korean and Caucasian male participants.
Part A (SAD): Area under concentration curve from time 0 to the last quantifiable concentration [AUClast]
时间窗: Day 1 to Day 5
To characterize the AUClast of AJH-2947 after single oral dosing in healthy Korean and Caucasian male participants.
Part A (SAD): Maximum observed concentration [Cmax]
时间窗: Day 1 to Day 5
To characterize the Cmax of AJH-2947 after single oral dosing in healthy Korean and Caucasian male participants
Part A (SAD): Plasma concentrations of AJH-2947
时间窗: Day 1 to Day 5
To characterize the plasma concentration of AJH-2947 after single oral dosing in healthy Korean and Caucasian male participants.
Part B (MAD): Plasma concentrations of AJH-2947
时间窗: Day 1 to Day 18
To characterize the plasma concentration of AJH-2947 following oral administration of multiple ascending doses in healthy Korean and Caucasian male participants.
Part B (MAD): Time of maximum observed concentration [Tmax]
时间窗: Day 1 to Day 18
To characterize the Tmax of AJH-2947 following oral administration of multiple ascending doses in healthy Korean and Caucasian male participants.
Part A (SAD): Time to reach peak or maximum observed concentration [Tmax]
时间窗: Day 1 to Day 5
To characterize the Tmax of AJH-2947 after single oral dosing in healthy Korean and Caucasian male participants.
Part B (MAD): Maximum observed concentration [Cmax]
时间窗: Day 1 to Day 18
To characterize the Cmax of AJH-2947 following oral administration of multiple ascending doses in healthy Korean and Caucasian male participants.
Part B (MAD): Heat pain Threshold (The temperature at which the subject first perceives pain, ℃)
时间窗: Predose, Day 1, Day 7, and Day 8
Heat pain Threshold is determined by gradually increased the temperature of the thermal probe on non-sensitized and casaicin-sensitized skin starting from 30 ℃ as the baseline using Thermal NeuroSensory Analyzer. (The cutoff limit is set at 50°C)
Part B (MAD): Heat pain tolerance (The Maximum temperature that the subject can tolerate, ℃)
时间窗: Predose, Day 1, Day 7, and Day 8
Heat pain tolerance is determined by gradually increased the temperature of the thermal probe on non-sensitized and casaicin-sensitized skin starting from 30 ℃ as the baseline using Thermal NeuroSensory Analyzer. (The cutoff limit is set at 50°C)
Part B (MAD): The partial area from dosing time to dosing time plus dosing interval [AUCτ]
时间窗: Day 1 to Day 18
To characterize the AUCτ of AJH-2947 following oral administration of multiple ascending doses in healthy Korean and Caucasian male participants.
Part B (MAD): Maximum observed concentration occurring at time Tmax,ss [Cmax,ss]
时间窗: Day 1 to Day 18
To characterize the Cmax,ss of AJH-2947 following oral administration of multiple ascending doses in healthy Korean and Caucasian male participants.
Part B (MAD): At steady state, the partial area from dosing time to dosing time plus dosing interval [AUCτ,ss]
时间窗: Day 1 to Day 18
To characterize the AUCτ,ss of AJH-2947 following oral administration of multiple ascending doses in healthy Korean and Caucasian male participants.
Part A (SAD): Maximum observed plasma concentration (Cmax)
时间窗: Day 1 to Day 7
To characterize the Cmax of AJH-2947 following a single oral dose under fed or fasted conditions.
Part A (SAD): Area under the concentration-time curve to the last quantifiable concentration (AUClast)
时间窗: Day 1 to Day 7
To characterize the AUClast of AJH-2947 following a single oral dose under fed or fasted conditions.
Part A (SAD): Area under the concentration-time curve extrapolated to infinity (AUCinf)
时间窗: Day 1 to Day 7
To characterize the AUCinf of AJH-2947 following a single oral dose under fed or fasted conditions.
Part B (MAD): Maximum observed plasma concentration following the first dose (Cmax)
时间窗: Day 1 to Day 2
To characterize the maximum observed plasma concentration (Cmax) of AJH-2947 following the first dose.
Part B (MAD): Area under the concentration-time curve over the dosing interval following the first dose (AUCtau)
时间窗: Day 1 to Day 2
To characterize the area under the plasma concentration-time curve over the dosing interval following the first oral dose (AUCtau) of AJH-2947.
Part B (MAD): Maximum observed plasma concentration at steady state (Cmax,ss)
时间窗: Day 7 to Day 8
To characterize the maximum observed plasma concentration at steady state (Cmax,ss) of AJH-2947 following once-daily oral administration for 7 consecutive days.
Part B (MAD): Area under the concentration-time curve over the dosing interval at steady state (AUCtau,ss)
时间窗: Day 7 to Day 8
To characterize the area under the plasma concentration-time curve over the dosing interval at steady state (AUCtau,ss) of AJH-2947 following once-daily oral administration for 7 consecutive days.
Number of participants with AEs, SAEs, and clinically significant safety findings
时间窗: From signing informed consent through the post-study visit (up to Day 18)
To assess safety and tolerability based on adverse events, vital signs, 12-lead ECGs, clinical laboratory tests, and physical examinations.
次要结局
- Part B (MAD): Number of participants with SAE(Day -1, Day 1 to day 18 (last visit))
- Part A (SAD): Number of participants with adverse events (AE)(Day -1, Day 1 to day 12 (last visit))
- Part A (SAD): Number of participants with serious adverse events (SAE)(Day -1, Day 1 to day 18 (last visit))
- Part B (MAD): Number of participants with AE(Day -1, Day 1 to day 18 (last visit))
- Part B (MAD): Heat pain threshold(Predose (Day -1), Day 1, and Day 7)
- Part B (MAD): Heat pain tolerance(Predose (Day -1), Day 1, and Day 7)