A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HW243040 in Healthy Participants

NCT07841522 | Not Yet Recruiting Phase 1

• 1 other identifier: HW243040-101
• Study Type: interventional
• Target: 98
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

HW243040; Angiotensin II Type 2 Receptor Antagonist; AT2R Antagonist; Healthy Volunteers; Pharmacokinetics; Single Ascending Dose; Multiple Ascending Dose; Food Effect

Outcome Measures

Primary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

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

  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 Clinically Significant Vital Signs Changes

  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

  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

  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).

Secondary Outcomes (37)

• 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.

Other Outcomes (1)

• Change from Baseline in QTcF Interval (ΔQTcF and ΔΔQTcF)

  Day 1: pre-dose at -30, -20, -10 minutes; and 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose (300 mg and above cohorts; 600 mg cohort only Sequence A in Period 1).

Study Arms (11)

HW243040 50mg Single Dose

EXPERIMENTAL

Participants receive a single oral dose of HW243040 50mg (one 50mg tablet) under fasting conditions on Day 1.

Drug: HW243040

HW243040 150mg Single Dose

EXPERIMENTAL

Participants receive a single oral dose of HW243040 150mg (three 50mg tablets) under fasting conditions on Day 1.

Drug: HW243040

HW243040 300mg Single Dose

EXPERIMENTAL

Participants receive a single oral dose of HW243040 300mg (six 50mg tablets or one 200mg + two 50mg tablets) under fasting conditions on Day 1.

Drug: HW243040

HW243040 600mg Single Dose (Fasting and Fed)

EXPERIMENTAL

Participants receive a single oral dose of HW243040 600mg (three 200mg tablets) in a two-period crossover design: one dose under fasting conditions and one dose under fed (high-fat, high-calorie meal) conditions, with a 7-day washout period between doses.

Drug: HW243040

HW243040 900mg Single Dose

EXPERIMENTAL

Participants receive a single oral dose of HW243040 900mg (one 200mg + one 50mg tablets, total 4.5 tablets) under fasting conditions on Day 1.

Drug: HW243040

HW243040 1200mg Single Dose

EXPERIMENTAL

Participants receive a single oral dose of HW243040 1200mg (six 200mg tablets) under fasting conditions on Day 1.

Drug: HW243040

Placebo Single Dose

PLACEBO COMPARATOR

Participants receive a single oral dose of HW243040 matching placebo tablets (number of tablets matching the corresponding active dose group) under fasting conditions on Day 1.

Drug: HW243040 Matching Placebo

HW243040 150mg BID Multiple Doses

EXPERIMENTAL

Participants receive HW243040 150mg (three 50mg tablets) orally twice daily (every 12 hours) for 5 days (9 doses total, Day 1 to Day 5 morning) under fasting conditions.

Drug: HW243040

HW243040 300mg BID Multiple Doses

EXPERIMENTAL

Participants receive HW243040 300mg (six 50mg tablets or one 200mg + two 50mg tablets) orally twice daily (every 12 hours) for 5 days (9 doses total, Day 1 to Day 5 morning) under fasting conditions.

Drug: HW243040

HW243040 600mg BID Multiple Doses

EXPERIMENTAL

Participants receive HW243040 600mg (three 200mg tablets) orally twice daily (every 12 hours) for 5 days (9 doses total, Day 1 to Day 5 morning) under fasting conditions.

Drug: HW243040

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.

Drug: HW243040 Matching Placebo

Interventions

HW243040 DRUG

HW243040 tablets, 50mg and 200mg规格, administered orally. Doses range from 50mg to 1200mg as a single dose in Part A, or 150mg to 600mg twice daily for 5 days in Part B. Administered with 240mL water under fasting or fed (high-fat, high-calorie meal) conditions as specified per arm.

HW243040 1200mg Single Dose; HW243040 150mg BID Multiple Doses; HW243040 150mg Single Dose; HW243040 300mg BID Multiple Doses; HW243040 300mg Single Dose; HW243040 50mg Single Dose; HW243040 600mg BID Multiple Doses; HW243040 600mg Single Dose (Fasting and Fed); HW243040 900mg Single Dose

HW243040 Matching Placebo DRUG

HW243040 matching placebo tablets, 50mg and 200mg规格, identical in appearance to HW243040 active tablets. Administered orally with 240mL water under the same conditions as the corresponding active dose arm.

Placebo BID Multiple Doses; Placebo Single Dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• \. 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).
• \. 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.
• \. 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.

Sponsors & Collaborators

• The Third Xiangya Hospital of Central South University: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Pharmacology

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 25, 2026
• Study Start: September 30, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share