JKN2306 in Healthy Subjects: Single Ascending Dose and Food Effect Study

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.