临床试验/NCT07841522

NCT07841522尚未招募1 期

A Phase I, Randomized, Double-Blind, Single-Center, Dose-Escalation, Placebo-Controlled Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HW243040 in Healthy Participants

The Third Xiangya Hospital of Central South University0 个研究点目标入组 98 人开始时间: 2026年9月30日最近更新: 2026年9月25日

适应症

干预措施

试验速览

阶段: 1 期
状态: 尚未招募
发起方: The Third Xiangya Hospital of Central South University
入组人数: 98
主要终点: Number of Participants with Clinically Significant Vital Signs Changes

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

This is a Phase I, randomized, double-blind, placebo-controlled, single-center, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HW243040 in healthy participants. The study consists of two parts: Part A (Single Ascending Dose, SAD) and food effect study, and Part B (Multiple Ascending Dose, MAD). A total of approximately 98 healthy participants will be enrolled.

详细描述

This is a first-in-human, Phase I, randomized, double-blind, placebo-controlled, single-center, dose-escalation clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HW243040, a novel angiotensin II type 2 receptor (AT2R) antagonist, in healthy participants. Preclinical data have demonstrated that HW243040 exhibits good analgesic efficacy in neuropathic pain models with a favorable safety profile, supporting its further clinical development. This study does not aim to explore the maximum tolerated dose (MTD) but focuses on characterizing the safety and PK profile across a range of doses.

The study is divided into two main parts: Part A (Single Ascending Dose, SAD, combined with a Food Effect evaluation) and Part B (Multiple Ascending Dose, MAD) . A total of approximately 98 healthy participants are planned for enrollment across both parts.

Part A: SAD and Food Effect Study Part A consists of 6 dose cohorts: 50 mg, 150 mg, 300 mg, 600 mg, 900 mg, and 1200 mg. Except for the 600 mg cohort, each cohort enrolls 10 participants (8 receiving active HW243040 and 2 receiving placebo) under fasting conditions. The 600 mg cohort enrolls 18 participants (16 active, 2 placebo) and utilizes a two-period, two-sequence crossover design to evaluate the effect of a high-fat, high-calorie meal on the PK of HW243040. In this cohort, participants receive the study drug under fasting conditions in one period and under fed conditions in the other, with a 7-day washout between periods. Dose escalation proceeds sequentially from the lowest to the highest dose, with dose progression decisions made by a Safety Review Committee (SRC) based on review of safety and available PK data from the preceding cohort. Dose escalation will be halted if predefined stopping criteria are met (e.g., ≥1/2 participants with moderate related AEs, ≥1/3 with severe related AEs, or any related SAE).

Part B: MAD Study Based on the safety and PK results from Part A, Part B evaluates three dose levels of HW243040 administered twice daily (BID). The planned dose levels are 150 mg, 300 mg, and 600 mg BID. Each cohort enrolls 10 participants (8 active, 2 placebo). Participants receive the study drug for 5 consecutive days (morning and evening, approximately 12 hours apart, for a total of 9 administrations, with only the morning dose given on Day 5). The final dosing regimen, duration, and sampling schedule for Part B may be adjusted based on emerging data from Part A.

Study Population:

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Sequential
主要目的: Other
盲法: Triple (Participant, Investigator, Outcomes Assessor)

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

•Signed informed consent form prior to any study-related procedures, with full understanding of the study content, procedures, and potential adverse reactions, and ability to complete the study as per protocol requirements.
•Healthy male or female, aged ≥ 18 and ≤ 55 years on the day of signing the informed consent form.
•Body weight: males ≥ 50 kg, females ≥ 45 kg; body mass index (BMI) between 19 and 26 kg/m² inclusive (BMI = weight (kg) / height² (m²)).
•Vital signs, physical examination, laboratory tests (hematology, blood biochemistry, urinalysis, coagulation function, and thyroid function), and 12-lead electrocardiogram (ECG) findings are normal or clinically insignificant at screening and baseline.
•Abdominal ultrasound, thyroid ultrasound, and chest X-ray findings are normal or clinically insignificant at screening.
•Willing and able to undergo pain testing procedures and trained qualified.
•Female participants of childbearing potential and male participants with partners of childbearing potential must have adopted contraceptive measures within 2 weeks prior to signing the informed consent form, and must agree to remain abstinent or use highly effective contraceptive methods from the signing of the informed consent form through the end of the follow-up period.
•Female participants of childbearing potential must agree to use highly effective contraceptive methods during the study and for 3 months after the last dose; serum pregnancy test must be negative at screening and baseline, and must not be breastfeeding. Male participants must agree to use highly effective contraceptive methods and refrain from sperm donation during the study and for 3 months after the last dose.

排除标准

•1. Presence of any of the following diseases or treatment history:
•Current or previous history of any clinically significant disease involving the urinary, cardiovascular, endocrine, neurological, digestive, respiratory, hematopoietic, immune, psychiatric, or metabolic systems, or any other condition that, in the investigator's judgment, may interfere with the study results, such as intestinal diseases (including irritable bowel syndrome) and urinary tract infections.
•History of malignancy (except for cancers that have been cured or in remission for ≥ 5 years, radically resected basal cell or squamous cell skin carcinoma, in situ cervical carcinoma, and resected colon polyps).
•Any condition or disease that, in the investigator's judgment, may affect the absorption, metabolism, and/or excretion of the study drug.
•Severe infection, severe trauma, or major surgery within 3 months prior to screening or baseline, or planned surgery during the study period.
•Use of any medication (including prescription drugs, over-the-counter drugs, herbal medicines, dietary supplements, vitamin A and its derivatives, etc., except for routine vitamins and occasional use of acetaminophen) within 2 weeks prior to screening or baseline, or still within 5 half-lives of the drug at screening or baseline (whichever is longer); or planned use of non-study medications during the study period.
•Participation in any other drug or medical device clinical trial within 3 months prior to screening or baseline, or planned participation during the study period, or still within 5 half-lives of the investigational drug at screening or baseline (whichever is longer).
•2. Any of the following laboratory findings at screening:
•Sitting systolic blood pressure < 90 mmHg or sitting diastolic blood pressure < 50 mmHg at screening or baseline.
•Orthostatic hypotension confirmed by repeat measurement within 15 minutes at screening or baseline.
•Clinically significant 12-lead ECG abnormalities at screening or baseline; QTcF > 450 ms for males or QTcF > 460 ms for females.
•Positive for hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV) antibody, syphilis antibody, or hepatitis C virus (HCV) antibody at screening.
•3. General conditions:
•Blood donation or significant blood loss (≥ 400 mL) within 8 weeks prior to screening or baseline, or blood transfusion within 4 weeks prior to screening or baseline; or intention to donate blood during the study period.
•Vaccination within 2 weeks prior to screening or baseline, or planned vaccination during the study period.
•Smoking history (average > 5 cigarettes per day) within 4 weeks prior to screening or baseline, or inability to refrain from using any tobacco products during the study period.
•Average daily alcohol intake > 15 g within 4 weeks prior to screening or baseline (15 g alcohol is equivalent to approximately 450 mL beer, 150 mL wine, or 50 mL liquor), or inability to abstain from alcohol during the study period; or positive breath alcohol test at baseline.
•History of drug abuse or dependence prior to screening or baseline; or positive urine drug screen at baseline.
•Excessive consumption of tea, coffee, or caffeinated beverages (average > 8 cups per day, 250 mL per cup) within 6 months prior to screening or baseline.
•Consumption of special foods (such as grapefruit, grapefruit juice, or foods/beverages containing grapefruit juice, chocolate, tobacco, alcohol, caffeinated foods or beverages, etc.) within 48 hours prior to baseline.
•Special dietary requirements or inability to comply with the standardized diet provided by the study center.
•Dysphagia, difficulty in venous blood collection, or physical condition unable to tolerate intensive blood sampling.
•Known allergy to any component of the investigational medicinal product; history of allergic diseases or allergic constitution.
•Use of strong or moderate inhibitors/inducers of CYP2C9, or any inhibitors of P-gp, OATP1B1, OATP1B3, or OAT3 within 30 days prior to screening or planned during the study period.
•Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in this study, including but not limited to any physiological or psychological condition that may increase the risk of the study, affect the participant's compliance with the protocol, or affect the participant's ability to complete the study.

干预措施: HW243040 (Drug)

Placebo BID Multiple Doses

Placebo Comparator

Participants receive HW243040 matching placebo tablets orally twice daily (every 12 hours) for 5 days (9 doses total, Day 1 to Day 5 morning) under fasting conditions.

干预措施: HW243040 Matching Placebo (Drug)

结局指标

主要结局

Number of Participants with Clinically Significant Vital Signs Changes

时间窗: Baseline (Day -1) to End of Study; measured at screening, Day -1, pre-dose and 1, 2, 4, 8, 12, 24, 48, 72 hours post-dose (schedule varies per cohort).

Number of Participants with Clinically Significant Laboratory Abnormalities

时间窗: Baseline (Screening) to End of Study (Day 4 for SAD 50/150/300/900/1200 mg; Day 11 for 600 mg FE; Day 8 for MAD).

Number of Participants with Clinically Significant 12-lead ECG Abnormalities

时间窗: Baseline (Day -1) to End of Study; measured at screening, Day -1, pre-dose and 1, 2, 4, 8, 12, 24, 48, 72 hours post-dose (schedule varies per cohort).

Incidence of Treatment-Emergent Adverse Events (TEAEs)

时间窗: From signing of informed consent form through follow-up period (until AE resolution; up to Day 4 for SAD 50/150/300/900/1200 mg, Day 11 for 600 mg FE, Day 8 for MAD cohorts).

Number of participants with TEAEs, including serious adverse events (SAEs), assessed by CTCAE v5.0.

次要结局

Maximum Observed Plasma Concentration (Cmax) Following Single Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose.)
Time to Maximum Observed Plasma Concentration (Tmax) of HW243040 Following Single Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose.)
Apparent Terminal Elimination Half-life (t1/2) of HW243040 Following Single Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose.)
Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t) of HW243040 Following Single Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose.)
Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of HW243040 Following Single Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose.)
Apparent Total Clearance (CL/F) of HW243040 Following Single Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose.)
Apparent Volume of Distribution (Vz/F) of HW243040 Following Single Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose.)
Maximum Observed Plasma Concentration (Cmax) of HW243040 Following Single Dose in Fed and Fasted States(Period 1 (Day 1) and Period 2 (Day 8): pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose in each period (two-way crossover, fasted vs fed).)
Time to Maximum Observed Plasma Concentration (Tmax) of HW243040 Following Single Dose in Fed and Fasted States(Period 1 (Day 1) and Period 2 (Day 8): pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose in each period (two-way crossover, fasted vs fed).)
Apparent Terminal Elimination Half-life (t1/2) of HW243040 Following Single Dose in Fed and Fasted States(Period 1 (Day 1) and Period 2 (Day 8): pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose in each period (two-way crossover, fasted vs fed).)
Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t) of HW243040 Following Single Dose in Fed and Fasted States(Period 1 (Day 1) and Period 2 (Day 8): pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose in each period (two-way crossover, fasted vs fed).)
Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of HW243040 Following Single Dose in Fed and Fasted States(Period 1 (Day 1) and Period 2 (Day 8): pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose in each period (two-way crossover, fasted vs fed).)
Apparent Total Clearance (CL/F) of HW243040 Following Single Dose in Fed and Fasted States(Period 1 (Day 1) and Period 2 (Day 8): pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose in each period (two-way crossover, fasted vs fed).)
Apparent Volume of Distribution (Vz/F) of HW243040 Following Single Dose in Fed and Fasted States(Period 1 (Day 1) and Period 2 (Day 8): pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose in each period (two-way crossover, fasted vs fed).)
Maximum Observed Plasma Concentration (Cmax) of HW243040 on Day 1 of Multiple Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose (12-hour sample is pre-dose for second administration).)
Time to Maximum Observed Plasma Concentration (Tmax) of HW243040 on Day 1 of Multiple Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose (12-hour sample is pre-dose for second administration).)
Area Under the Plasma Concentration-Time Curve from Time Zero to 12 Hours (AUC0-12h) of HW243040 on Day 1 of Multiple Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose (12-hour sample is pre-dose for second administration).)
Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of HW243040 on Day 1 of Multiple Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose (12-hour sample is pre-dose for second administration).)
Apparent Total Clearance (CL/F) of HW243040 on Day 1 of Multiple Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose (12-hour sample is pre-dose for second administration).)
Apparent Volume of Distribution (Vz/F) of HW243040 on Day 1 of Multiple Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose (12-hour sample is pre-dose for second administration).)
Apparent Terminal Elimination Half-life (t1/2) of HW243040 on Day 1 of Multiple Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose (12-hour sample is pre-dose for second administration).)
Area Under the Plasma Concentration-Time Curve over One Dosing Interval (AUC0-tau) of HW243040 on Day 1 of Multiple Ascending Dose Administration(Day 1: pre-dose (within 30 minutes) and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose (12-hour sample is pre-dose for second administration).)
Area Under the Plasma Concentration-Time Curve over a Dosing Interval at Steady State (AUCtau,ss) of HW243040(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Apparent Clearance at Steady State (CLss/F) of HW243040(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration at Steady State (AUC0-t,ss) of HW243040(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity at Steady State (AUC0-inf,ss) of HW243040(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of HW243040(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Apparent Terminal Elimination Half-life (t1/2) of HW243040 at Steady State(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Apparent Volume of Distribution at Steady State (Vz/F) of HW243040(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Trough Concentration at Steady State (Ctrough,ss) of HW243040(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Peak Concentration at Steady State (Cmax,ss) of HW243040(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Accumulation Ratio (Rac) of HW243040 at Steady State(Day 3, Day 4, and Day 5: pre-dose (morning troughs); Day 5: pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-morning dose; plus 24 hours (Day 6), 48 hours (Day 7), and 72 hours (Day 8) post-morning dose on Day 5.)
Cumulative Amount of Unchanged HW243040 Excreted in Urine (Ae)(Period 1 (Day 1): pre-dose (within 12 hours) and 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours post-dose.)
Cumulative Amount of Unchanged HW243040 Excreted in Feces (Ae)(Period 1 (Day 1): pre-dose (within 12 hours) and 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours post-dose.)
Fraction of Unchanged HW243040 Excreted in Urine (fe)(Period 1 (Day 1): pre-dose (within 12 hours) and 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours post-dose.)
Fraction of Unchanged HW243040 Excreted in Feces (fe)(Period 1 (Day 1): pre-dose (within 12 hours) and 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours post-dose.)
Renal Clearance (CLR) of HW243040(Period 1 (Day 1): pre-dose (within 12 hours) and 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours post-dose.)

研究者

发起方

The Third Xiangya Hospital of Central South University

申办方类型

Other

责任方

Principal Investigator

主要研究者

Guoping Yang

Professor of Clinical Pharmacology

The Third Xiangya Hospital of Central South University

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