A Phase 3 Trial of K-924 HD in Participants with Hypercholesterolemia with Inadequate Response to EU-Marketed Pitavastatin 4 mg

Lab values

• (1) Participants with a history of myopathy or rhabdomyolysis caused by pitavastatin or ezetimibe (2) Participants with a history of hypersensitivity to pitavastatin, ezetimibe or any excipient in formulations of either drug. (3) Participants with serious hepatic disorder (Child Pugh classification B or higher) or biliary obstruction. (4) POCBP who is known to be pregnant, has a positive serum pregnancy test, is lactating and breastfeeding, planning to become pregnant or breastfeed during the trial, and who do not agree to use an acceptable method of contraception. POCBP must use one of the acceptable birth control methods as specified in Section 13.1.2 before enrollment, throughout the trial, and until ≥30 days after the last dose of trial intervention. (5) Participants whose compliance with EU-marketed pitavastatin 4 mg during the screening period was <80% or >120% (6) Participants whose CK is ≥3 × ULN at Visit 1 or Visit 1’. (7) Participants whose ALT and AST are both ≥2 × ULN at Visit 1 or Visit 1’. (8) Participants who meet any of the following conditions: - Type 1 diabetes - Poorly controlled type 2 diabetes defined as HbA1c >10% at Visit 1 or Visit 1’. (9) Participants with poorly controlled hypertension defined as SBP ≥160 mmHg or DBP ≥100 mmHg at Visit 1 or Visit 1’. (10) Participants with eGFR (CKD-EPI) <30 mL/min/1.73 m2 at Visit1 or Visit 1’, or those who are on dialysis. (11) Participants with heart failure with NYHA classification ≥III. (12) Participants who have had any of the following within 3 months prior to IC: - myocardial infarction, severe or unstable angina, coronary angioplasty, coronary artery bypass surgery, stroke, transient ischemic attack, symptomatic carotid stenosis, symptomatic peripheral arterial disease, abdominal aortic aneurysm, severe arrhythmia with poorly controlled, decompensated heart failure, symptomatic cardiac arrhythmia (or medication for arrythmia that was started or dose was changed), carotid surgery or stenting, endovascular procedure or surgical intervention for peripheral vascular disease. (13) Participants scheduled to undergo a major surgical or interventional procedure (e.g. PCI, CABG, carotid or peripheral revascularization). (14) Participants with thyroid disease. Those who are considered to be well-controlled based on the Investigator’s discretion are permitted to participate.
• (15) Participants with homozygous familial hypercholesterolemia (16) Participants who have known cancer complications or a history of malignancy within the 5 years prior to IC (except for non-invasive cancer or other stable, relatively benign conditions). (17) Participants who have donated blood or who have had a major trauma, blood transfusion, or major surgery within 30 days prior to Visit 1. (18) Participants with previous history of clinically meaningful allergic reactions to a medication or study drug requiring treatment, in the judgement of the Investigator (e.g., anaphylactic shock). (19) Participants who are required to receive concomitantly prohibited drugs after signing the ICF and during the trial period. (20) Participants whose fasting serum TG ≥400 mg/dL (4.5 mmol/L) at Visit 1 or Visit 1’. (21) Participants who are undergoing or plans to initiate an LDL-C apheresis. (22) Participants with a known history of HIV-1 or HIV-2 infection. (23) Participants who meet any of the following conditions within 5 years prior to Visit 1: - Have been treated for HCV. - Have active HCV infection defined as HCV antibody positive and presence of HCV-RNA. - Have active HBV infection defined as HBsAg positive (24) Participants who have active HAV infection defined as HAV antibody positive, or have been cured of <3 months prior to Visit 1. (25) Participants with malabsorption or with a history of malabsorption, or who have undergone other surgical procedures of the gastrointestinal tract, including weight loss surgery such as Lap-Band or gastric bypass surgery (excluding appendicectomy, hernia repair, etc.) that may have affected absorption. (26) Participants who have a history of alcoholism or drug addiction within 2 years prior to IC. (27) Participants who participated in another clinical trial within 16 weeks prior to the administration of the trial intervention or 5 x half-life of the active ingredient, whichever is longer, and who received an investigational medicinal product other than a placebo that does not contain the active ingredient or those who plan to participate in another clinical trial concurrently with this one. (28) Participants deemed to be inappropriate for participation by the Investigators.

• (1) Participants with hypercholesterolemia who are aged ≥18 years at the time of signing the ICF. (2) Participants who have been instructed to follow a certain diet and/or exercise regimen, taking into account regional, national or local guidelines, and been continuing the regimen without changes per Investigator’s judgement for ≥4 weeks prior to Visit 1. (3) Participants whose fasting LDL-C (Friedewald formula) at Visit 1 or Visit 1’, performed under pitavastatin 4 mg/day stable administration for ≥4 weeks, meets one of the following criteria: a. Low risk: fasting LDL-C of ≥116 mg/dL (≥3.0 mmol/L) b. Moderate risk: fasting LDL-C of ≥100 mg/dL (≥2.6 mmol/L) c. High risk: fasting LDL-C of ≥70 mg/dL (≥1.8 mmol/L) d. Very high risk: fasting LDL-C of ≥55 mg/dL (≥1.4 mmol/L) e. Extreme risk: fasting LDL-C of ≥40 mg/dL (≥1.0 mmol/L) (4) Participants who have been receiving any of the following statins for ≥2 weeks at the time of IC. a. Atorvastatin ≥20 mg/day b. Pitavastatin 4 mg/day c. Rosuvastatin ≥5 mg/day d. Simvastatin ≥40 mg/day