A Phase I Trial of QLS1410 in Healthy Chinese Adults and Participants With Mild Essential Hypertension

Prior treatment

• Use of systemic corticosteroids within 3 months prior to screening.
• Smoking \>5 cigarettes/day on average within 6 months before screening, or current use of e-cigarettes.
• Alcohol consumption \>14 units/week (1 unit = 360 mL of beer, 45 mL of 40% spirits, or 150 mL of wine) within 6 months before screening, or has a positive breath alcohol test at screening.
• Blood donation \>400 mL within 3 months or \>200 mL within 4 weeks before screening, or plan to donate blood during the study.
• Use of strong CYP3A4 or CYP1A2 inhibitors within 7 days or 5 half-lives (whichever is longer) before screening. Use of strong CYP3A4 inducer within 14 days or 5 half-lives (whichever is longer) before screening.
• Use of any prescription drugs, OTC drugs, traditional medicines, and dietary supplements within 2 weeks or 5 half-lives (whichever is longer) prior to randomization.

Other illness

• Any medical condition/disease at screening deemed by the investigator to require exclusion, including but not limited to the nervous, psychiatric, cardiovascular, hematologic/lymphatic, immune, respiratory, digestive, urinary, metabolic and skeletal systems.
• Dysphagia or any surgical condition/disease that may affect drug absorption, distribution, metabolism, or excretion, at screening.
• Mean pulse/heart rate (HR) \>100 or \<50 bpm after ≥5 min of rest at screening (measured 3 times consecutively).
• Inability to tolerate a high-fat meal (for Part B only).
  • Part C: Participants with Mild Essential Hypertension
• Secondary hypertension.
• Orthostatic tachycardia or hypotension at screening, or history of related symptoms (e.g., dizziness, weakness, blurred vision upon standing).
• History of syncope.
• Any other condition deemed unsuitable by the investigator.

Lab values

• Any laboratory abnormalities that meet the test requirements should be noted during screening (if necessary, retest can be conducted at least one week apart):
• Metabolic/cardiovascular disorders: 1) Diabetes (fasting glucose ≥7.0 mmol/L \[126 mg/dL\] or HbA1c ≥6.5%); 2) History of cardiovascular events (e.g., stroke, transient ischemic attack, myocardial infarction, unstable angina, coronary artery bypass grafting, percutaneous coronary intervention, heart failure hospitalization) or clinically significant valvular disease; 3) Personal/family history of long QT syndrome, torsades de pointes (TdP), arrhythmias, or sudden cardiac death; 4) Other conditions that may interfere with the study or increase risk, per investigator judgment.
• Laboratory abnormalities (as defined in Part A/B, with repeat testing allowed).

Other

• Part A \& Part B: Healthy Participants
• Pregnant/lactating females or positive pregnancy test at screening.

• Part A \& Part B: Healthy Participants
• Able to understand and willing to comply with all study visits, procedures, restrictions and provide the written informed consent form (ICF).
• Males and females aged 18 to 55 years, inclusive.
• Weight ≥ 50 kg for males and ≥ 45 kg for females, Body mass index (BMI) between 18 and 26 kg/m\^2, inclusive, at screening.
• Has a mean seated office systolic blood pressure (SBP) 110\~139 mmHg (inclusive) and diastolic blood pressure (DBP) 70\~89 mmHg (inclusive) at screening and baseline; measured 3 times consecutively (1-2 min intervals).
• QTcF (QT corrected using Fridericia's formula) \<450 ms for males and \<470 ms for females.
• Participants (including partners) must agree to abstain from sperm/egg donation and pregnancy plans, and to use highly effective contraception, from signing the ICF until 3 months after receiving the last dose of investigational product.
• Part C: Participants with Mild Essential Hypertension
• Able to understand and willing to comply with all study visits, procedures, restrictions and provide the ICF.
• Males and females aged 18 to 65 years (18 to 65 years in MAD study), inclusive.
• Weight ≥ 50 kg for males and ≥ 45 kg for females, BMI between 18 and 28 kg/m\^2, inclusive, at screening.
• Has a mean seated office SBP 140\~159 mmHg (inclusive) and DBP 85\~99 mmHg (inclusive) at screening and baseline; measured 3 times consecutively (1-2 min intervals).
• QTcF \<450 ms for males and \<470 ms for females.
• No use of antihypertensive medications (including ACEIs, ARBs, CCBs, ARNIs, diuretics, etc.) within 30 days prior to signing the ICF.
• Participants (including partners) must agree to abstain from sperm/egg donation and pregnancy plans, and to use highly effective contraception, from signing the ICF until 3 months after receiving the last dose of investigational product.