A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Food Effect of Single Oral Doses of JKN2306 Tablets in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Safety and tolerability of single oral doses of JKN2306
研究概览
简要总结
This first-in-human, single-center study in China evaluated the safety, tolerability, and pharmacokinetics of single oral doses of JKN2306 tablets in healthy adult subjects and assessed the effect of a high-fat, high-calorie meal on the pharmacokinetics of JKN2306.
详细描述
The study consisted of a single ascending dose (SAD) part and a food effect (FE) part. The SAD part was a single-center, randomized, double-blind, placebo-controlled study with five dose cohorts (10 mg, 30 mg, 100 mg, 200 mg, and 400 mg). The FE assessment was conducted sequentially in subjects participating in the 200 mg cohort using two dosing periods separated by a washout; dosing was performed under fasting conditions in Period 1 and under fed conditions (high-fat, high-calorie meal) in Period 2. Pharmacokinetic sampling and safety assessments were performed per protocol, and exploratory assessments included concentration-QTc analysis and metabolite profiling.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Chinese males or females aged 18 to 55 years (inclusive).
- •Body weight ≥50 kg for males and ≥45 kg for females; BMI 19.0 to 28.0 kg/m² (inclusive).
- •Able and willing to comply with study procedures and restrictions and to complete the study as planned.
- •Willing to use medically acceptable contraception and have no plan for pregnancy, sperm donation, or oocyte donation from signing informed consent through 90 days after the last dose.
排除标准
- •Participation in another clinical trial within 3 months prior to screening or planned participation during the study.
- •Clinically significant diseases or abnormalities that may affect safety or study participation; or conditions that may interfere with absorption, distribution, metabolism, or excretion (e.g., relevant gastrointestinal disorders).
- •History of photosensitivity or hypersensitivity/allergy to study drug components, other drugs, or foods.
- •Serious infection/major trauma/major surgery within 3 months prior to dosing, or planned surgery during the study; febrile illness or evidence of active infection within 2 weeks prior to first dose.
- •Use of medications that may affect hepatic drug metabolism within 28 days; use of prescription/OTC drugs, herbal products, vitamins, or supplements within 14 days prior to dosing or planned use during the study.
- •Consumption of grapefruit-related products/caffeine/alcohol and other specified dietary restrictions within 48 hours prior to first dose or unwillingness to comply with dietary restrictions.
- •Drug abuse history or positive drug screen; excessive alcohol use or positive breath alcohol test; excessive nicotine use or positive cotinine screen.
- •Clinically significant abnormalities in physical examination, vital signs, ECG, or laboratory tests (hematology/urinalysis/biochemistry/coagulation), imaging, or infectious disease screening; positive HBsAg, HCV Ab, syphilis Ab, or HIV Ag/Ab.
- •Pregnant or lactating females, or positive pregnancy test.
- •History of QTc prolongation or clinically significant ECG abnormalities; QTcF ≥450 ms (males) or ≥470 ms (females) confirmed on repeat measurement.
研究组 & 干预措施
JKN2306 400 mg (SAD)
JKN2306 400 mg
干预措施: JKN2306 (Drug)
JKN2306 400 mg (SAD)
JKN2306 400 mg
干预措施: Placebo (Drug)
JKN2306 10 mg (SAD)
JKN2306 10mg only, without placebo.
干预措施: JKN2306 (Drug)
JKN2306 30 mg (SAD)
JKN2306 30 mg
干预措施: JKN2306 (Drug)
JKN2306 30 mg (SAD)
JKN2306 30 mg
干预措施: Placebo (Drug)
JKN2306 100 mg (SAD)
JKN2306 100 mg
干预措施: JKN2306 (Drug)
JKN2306 100 mg (SAD)
JKN2306 100 mg
干预措施: Placebo (Drug)
JKN2306 200 mg (SAD + FE subset)
Period 1 (fasted): single oral dose under fasting conditions. Period 2 (fed): after washout (planned 7 days), subjects consume a high-fat, high-calorie meal within 30 minutes and take the assigned study product 30 minutes after starting the meal.
干预措施: JKN2306 (Drug)
JKN2306 200 mg (SAD + FE subset)
Period 1 (fasted): single oral dose under fasting conditions. Period 2 (fed): after washout (planned 7 days), subjects consume a high-fat, high-calorie meal within 30 minutes and take the assigned study product 30 minutes after starting the meal.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and tolerability of single oral doses of JKN2306
时间窗: SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.
Number of participants with treatment-related adverse events as assessed by CTCAE V5.0. An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatmentemergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
次要结局
- Pharmacokinetic parameter of JKN2306: Tmax(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)
- Pharmacokinetic parameter of JKN2306: Cmax(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)
- Pharmacokinetic parameter of JKN2306: T1/2(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)
- Pharmacokinetic parameter of JKN2306: AUC0-last(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)
- Pharmacokinetic parameter of JKN2306: AUC0-inf(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)
- Pharmacokinetic parameter of JKN2306: CL/F(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)
- Pharmacokinetic parameter of JKN2306: Vz/F(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)
- Pharmacokinetic parameter of JKN2306: Kel(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)
- Pharmacokinetic parameter of JKN2306: MRT(SAD: Baseline to Day 8 post-dose.FE: Baseline to Day 15 post-dose.)