A Multicenter, Randomized, Double-Blind Phase 3 Trial of KDF1901 in Patients With Essential Hypertension

Prior treatment

• History of serious cardiovascular events or interventions within 24 weeks prior to screening:
  • Myocardial infarction, unstable angina, coronary revascularization (PCI/CABG)
• History of cerebrovascular disorders within 24 weeks prior to screening:
  • Stroke, TIA, cerebral hemorrhage
• History of ocular conditions within 24 weeks prior to screening:
  • Retinal hemorrhage, optic neuropathy, severe visual impairment
• Diagnosis of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) within 48 weeks prior to screening
• Requiring long-term immunosuppressive therapy or systemic corticosteroids
• Requirement for prohibited medications (emergency drugs) during study period (Visit 1-6)
• Use of lithium therapy
• History or suspicion of drug or alcohol abuse
• Participation in other clinical trials or use of investigational products within 4 weeks prior to screening

Other illness

• History or presence of secondary hypertension or suspected secondary hypertension, including:
  • Aortic coarctation, pheochromocytoma, Cushing's syndrome, hyperaldosteronism, polycystic kidney disease
• Severe pulmonary, cardiac, or vascular conditions, such as:
  • Pulmonary hypertension, severe heart failure (NYHA class III or IV), hypertrophic cardiomyopathy, aortic aneurysm, thrombocytopathy
• Hereditary blood disorders or history of angioedema related to ACE inhibitors or ARBs
• Clinically significant conditions affecting drug absorption, distribution, metabolism, or excretion
• Heart failure NYHA class III or IV
• Known serious arrhythmias, including ventricular tachycardia or fibrillation
• Known autoimmune disease or connective tissue disorder
• Clinically significant renal, hepatic, or cardiovascular disease
• Clinically significant chronic inflammatory conditions
• History of major surgery or active GI disorders
• Known edematous disorders (e.g., untreated nephrotic syndrome)
• Hypersensitivity to study drugs, dihydropyridine-class CCBs, thiazide diuretics, or sulfonamides

Lab values

• History of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
• eGFR \<30 mL/min/1.73 m² or serum creatinine ≥2.0 mg/dL
• ALT or AST \>3× upper limit of normal (ULN)
• Serum K+ \<3.5 or \>5.5 mmol/L, Na+ \<135 mmol/L, Ca2+ \>10.5 or \<2.63 mmol/L
• Type 2 diabetes mellitus with HbA1c ≥9.0%

Age

• History of malignancy within 5 years prior to screening, except:
  • Successfully treated and in remission for ≥2 years, or
  • Basal cell carcinoma or squamous cell carcinoma of the skin

Other

• Mean sitting diastolic blood pressure (MSDBP) ≥110 mmHg at screening (Visit 1) or baseline (Visit 3)
• Difference in blood pressure between arms: MSSBP ≥20 mmHg and MSDBP ≥10 mmHg at screening
• Symptoms of orthostatic hypotension or risk of falls or syncope
• Severe anemia, leukopenia, or thrombocytopenia at screening
• Use of terfenadine or astemizole
• Pregnancy or lactation
• Women of childbearing potential or male participants not agreeing to use reliable contraception during study
• Judged by the investigator to be otherwise unsuitable for study participation

• Male or female participants aged ≥19 years at the time of screening.
• Participants who meet one of the following blood pressure criteria at screening:
  • If not currently receiving antihypertensive medication for at least 4 weeks (treatment-naïve):
  • Mean Sitting Systolic Blood Pressure (MSSBP) ≥160 mmHg and \<200 mmHg
  • If currently receiving antihypertensive medication:
  • MSSBP ≥140 mmHg and \<200 mmHg
  • For participants with cardiovascular disease, diabetes mellitus, or microalbuminuria (e.g., persistent proteinuria or hematuria), the range is:
  • MSSBP ≥130 mmHg and \<200 mmHg
• Willing and able to provide written informed consent prior to participation in the study.
• At baseline (Visit 3), participants must have MSSBP ≥140 mmHg and \<200 mmHg.
  • For participants with cardiovascular disease, diabetes mellitus, or microalbuminuria: MSSBP ≥130 mmHg and \<200 mmHg
• At least 70% compliance with run-in period medication, as assessed by tablet count.