Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of DW5421A/DW5421B Compared to Monotherapy of DW5421A

A Multicenter, Randomized, Double-blind, Active-controlled, Parallel, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of DW5421A/DW5421B Versus Monotherapy of DW5421A in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia

This is a multicenter, randomized, double-blind, active-controlled, parallel, phase III clinical trial to evaluate the efficacy and safety of combination therapy of DW5421A/DW5421B versus monotherapy of DW5421A in patients with primary hypercholesterolemia or mixed dyslipidemia.

The primary objective is to demonstrate the superiority of combination therapy of DW5421A/DW5421B over monotherapy of DW5421A by comparing the change in LDL-C at week 8 after administration. Approximately equal numbers of patients were randomized in a 1:1 ratio to receive combination therapy of DW5421A/DW5421B or monotherapy of DW5421A for 8 weeks. Efficacy and safety assessments were conducted at week 4 and week 8.

Inclusion Criteria:

- Subjects must meet all of the following criteria to be eligible for the study: [Screening]

1. Male or female aged ≥19 years
2. Subjects diagnosed with primary hypercholesterolemia or mixed dyslipidemia
3. Subjects who satisfy both of the following criteria at Visit 1: (1) Triglyceride (TG) < 400 mg/dL; (2) Low-density lipoprotein cholesterol (LDL-C) ≤ 250 mg/dL
4. At Visit 1, for subjects who are receiving hypercholesterolemia treatment, those who, in the investigator's judgment, can medically and appropriately discontinue their existing hypercholesterolemia treatment for the duration of the clinical trial.
5. Subjects who voluntarily provided written informed consent to participate in this clinical trial.

[Randomization]

1. If currently receiving hypercholesterolemia treatment, subjects who have undergone a washout period of at least 4 weeks prior to Visit 2.
2. Subjects who have implemented TLC for at least 4 weeks prior to Visit 2 and have continued TLC through Visit 3.
3. Subjects whose RIP IP compliance during the run-in period is between 70% and 130%.
4. Subjects whose central laboratory test results at Visit 2 meet the criteria.

Exclusion Criteria:

• Subjects who meet any of the following conditions will not be eligible to participate in this clinical trial:

  1. Presence of any of the following medical histories or past surgical histories:

  1. Acute arterial disease-related history (as of Visit 1, within the 12-week period preceding the visit including: Unstable angina, myocardial infarction, transient ischemic attack (TIA), cerebrovascular disease, coronary artery bypass graft (CABG), or percutaneous coronary intervention (PCI)) Exception: Subjects whose events occurred more than 12 weeks before Visit 1, have been adjudicated as cured, or are in a stable state (ex: managed with a stable drug dosage for at least 12 weeks prior to Visit 1) may be eligible.

  2. Hypersensitivity or prior exposure to the investigational product's active ingredients (pitavastatin, ezetimibe) or to any dyslipidemia-treating agents.

  3. History of fibromyalgia, myopathy, rhabdomyolysis, or other hereditary myopathies, or a family history of such conditions.

  4. Severe heart failure (NYHA functional class III or IV).

  5. Any surgical or internal medical condition that could affect the absorption, distribution, metabolism, or excretion of the investigational drug (excluding uncomplicated appendectomy or hernia repair).

  6. A history of drug or alcohol abuse within 1 year prior to Visit 1.

  7. A history of malignancy (however, the following cases are eligible for participation):

     ① If at least 5 years have passed since completion of treatment for the tumor as of Visit 1, or if the subject is disease-free status.

     ② If at least 3 years have passed as of Visit 1 since complete excision of basal cell carcinoma or squamous cell carcinoma of the skin, curative resection of papillary thyroid carcinoma, or successful treatment of cervical carcinoma in situ.

  2. Subjects with the following comorbidities:

  1. Uncontrolled hypertension (SBP ≥ 180 mmHg or DBP ≥ 110 mmHg)
  2. Uncontrolled diabetes mellitus (HbA1c ≥ 9%)
  3. Uncontrolled thyroid dysfunction (TSH ≥ 1.5 × ULN)
  4. Hepatic dysfunction (AST or ALT ≥ 2 × ULN)
  5. Renal impairment (eGFR < 30 mL/min/1.73 m²)
  6. CK ≥ 2 × ULN
  7. Biliary obstruction or cholestasis
  8. Moderate hepatic disease or active liver disease
  9. Hypothyroidism
  10. Uncontrolled arrhythmia, as determined by the investigator
  11. Interstitial lung disease 3. Subjects who are administrating or are expected to administer concomitant medications prohibited by this clinical trial.

  4. Subjects with chronic conditions requiring continuous use of systemic corticosteroids or immunosuppressants.

  5. Subjects with secondary dyslipidemia due to conditions such as Cushing's syndrome, hypothyroidism, obstructive liver disease, or nephrotic syndrome.

  6. Contraception and pregnancy:

  1. Pregnant or breastfeeding women, or those planning to become pregnant or breastfeed during the clinical trial period.
  2. Women of childbearing potential and men who do not agree to use appropriate contraception as specified in the protocol during the clinical trial period.

  7. Subjects who have participated in another clinical trial and administered investigational product (or undergone an investigational medical device procedure) within 12 weeks prior to screening (however, enrollment may be permitted if participation was limited to an observational or retrospective study and, in the investigator's judgment, does not affect the efficacy or safety of this clinical trial).

  8. Subjects deemed unsuitable for participation in this clinical trial at the investigator's discretion.