A Phase I Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of KR23248 Capsules in Healthy Adult Subjects

Official title

A Randomized, Double-blind, Placebo-controlled, Dose-escalating Phase I Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of Single and Multiple Doses of KR23248 Capsules in Healthy Adult Subjects

Overview

This study aims to investigate the safety, tolerability and pharmacokinetic characteristics of KR23248 capsules in healthy subjects. This study will be conducted in China. It will enroll male and female participants aged 18 years to 45 years.

Detailed description

This study is a randomized, double-blind, placebo-controlled, dose-escalating Phase I trial, aiming to evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of single and multiple oral doses of KR23248 capsules in healthy adult subjects. The study consists of two parts: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies.

The single ascending dose study plans to enroll 54 healthy subjects, with predefined dose escalation levels of 0.5 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg in sequence. The multiple ascending dose study sets the initial dose at 2.0 mg, with 12 healthy subjects planned for enrollment.

Interventions

• Drug KR23248
  Participants will recieve a single oral dose of KR23248
• Drug Matching Placebo
  Participants will recieve placebo

Primary outcome measures

• Incidence of adverse events (AEs), serious adverse events（SAEs）, drug-related AEs, and AEs leading to study withdrawal [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]

Secondary outcome measures (12)

• Cmax [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]
• Tmax [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]
• t1/2 [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]
• λz [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]
• AUC0-t [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]
• AUC0-∞ [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]
• CL/F [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]
• Vd/F [Time frame: SAD:Day 1 to Day14 MAD:Day1 to Day28]
• MRT [Time frame: SAD: Day1 to D14 MAD:Day1 to Day28]
• Css_min [Time frame: MAD:Day1 to Day28]
• Css_max [Time frame: MAD:Day1 to Day28]
• Tss,max [Time frame: MAD:Day1 to Day28]

Eligibility criteria

Inclusion criteria

• Healthy male/female subjects aged ≥ 18 years and ≤ 45 years (inclusive) at the time of signing the informed consent form.
• Body Mass Index (BMI) ranging from 18.5 to 28.0 kg/m² (inclusive) at screening; male subjects with body weight ≥50 kg and female subjects with body weight ≥45 kg.
• Subjects who voluntarily participate in the trial and sign the informed consent form after understanding the purpose, content, procedures, and potential risks of the trial.
• Subjects who can communicate well with the investigators, are willing and able to comply with lifestyle restrictions specified in the protocol, and cooperate with study procedures.

Exclusion criteria

• Subjects with any diseases or dysfunctions in present illness and medical history that may interfere with the clinical trial, including but not limited to neurological and psychiatric diseases, cardiovascular diseases (e.g., congenital long QT syndrome), urinary system disorders, digestive system disorders, respiratory system disorders, musculoskeletal system disorders, metabolic and endocrine system disorders, skin diseases, hematological diseases, immune system diseases, and tumors.
• Subjects with any surgical condition or medical history that may significantly affect drug absorption, distribution, metabolism and excretion, or may pose a risk to the subject participating in the trial; such as a history of gastrointestinal surgery (gastrectomy, gastroenterostomy, enterectomy, etc.), urinary tract obstruction or dysuria, gastroenteritis, peptic ulcer, and history of gastrointestinal bleeding.
• Subjects with a history of severe allergic reactions or known hypersensitivity to any ingredients of the investigational product.
• Subjects with current or previous psychiatric disorders or cerebral dysfunction; those assessed to be at suicide risk based on the Columbia-Suicide Severity Rating Scale (C-SSRS), or by the investigator's clinical assessment, or those with a history of self-harm behavior.
• Subjects with a history of substance abuse within 1 year prior to administration or with a positive urine drug screening result.
• Subjects with a history of alcohol abuse within 6 months prior to screening (i.e., more than 14 standard units per week; 1 standard unit = 360 mL beer, or 45 mL spirits with 40% alcohol content, or 150 mL wine); or with a positive breath alcohol test; or unwilling to abstain from alcohol and any alcohol-containing products from screening until the last PK blood collection.
• Subjects with a history of surgery within 3 months prior to screening, or who have not recovered from surgery, or have a planned surgery scheduled during the trial.
• Subjects who have donated blood or experienced blood loss ≥ 400 mL within 3 months prior to screening, or ≥ 200 mL within one month, or have a history of blood product transfusion.
• Subjects who have participated in any clinical trial and received investigational drugs or medical devices within 3 months prior to screening.
• Subjects who have received vaccination within 30 days prior to screening, or have a vaccination plan during the entire study period.
• Subjects who have taken any medications within 28 days or 5 half-lives (whichever is longer) prior to screening and during the entire study period, including prescription drugs, over-the-counter drugs, herbal medicines, and any drugs that inhibit or induce hepatic drug-metabolizing enzymes (e.g., inducers and/or inhibitors of CYP3A4, CYP2D6, and CYP3A5).
• Female subjects who are pregnant, breastfeeding, or have a positive pregnancy test; or those who refuse to adopt effective non-pharmacological contraceptive measures (e.g., abstinence, intrauterine device, condoms with vaginal spermicide) throughout the study period and within 28 days after the end of administration; or those with a plan to donate sperm or ova.
• Subjects with clinically significant abnormal findings judged by the investigator in comprehensive physical examination, vital signs, laboratory tests and 12-lead electrocardiogram; including but not limited to: QTc > 450 ms in males and > 470 ms in females (Fridericia correction); resting pulse rate < 55 beats/min or > 100 beats/min; systolic blood pressure < 90 mmHg or ≥ 140 mmHg; diastolic blood pressure < 60 mmHg or ≥ 90 mmHg.
• Subjects with non-negative results for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV-Ab), Human Immunodeficiency Virus antibody (HIV-Ab), and Toluidine Red Untreated Serum Test (TRUST).
• Subjects with alanine transaminase (ALT), creatinine (Cr) or serum prolactin level exceeding 2 times the upper limit of normal during the screening period.
• Subjects who smoke an average of ≥ 5 cigarettes per day within 3 months prior to screening, or are unable to abstain from any tobacco products during the trial.
• Subjects with an average daily intake of ≥ 5 cups of coffee or tea (200 mL per cup) within 3 months prior to screening, or are unable to discontinue intake during the trial.
• Subjects with special dietary requirements who cannot follow a unified study diet, or have difficulty in swallowing.
• Subjects who have consumed food or beverages containing grapefruit and/or pomelo within 7 days prior to administration.
• Subjects who have consumed xanthine-rich food or beverages (e.g., tea, coffee, cola, chocolate) within 3 days prior to administration.
• Subjects with poor compliance or other conditions deemed unsuitable for participation in the trial by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07585383 · KR23248-202509

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗