Efficacy and Safety of K-924 in Participants with Hypercholesterolemia with Inadequate Response to Pitavastatin 4 mg: A Phase 3, Randomized, Active-Controlled Trial
- Trial ID
- 2025-523739-20-00
- Protocol
- K-924-3.01
- Sponsor
- Kowa Co. Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of K-924 HD by assessing LDL-C levels, calculated via the Friedewald formula, in participants with hypercholesterolemia who have demonstrated an inadequate response to 4 mg of pitavastatin over a 12-week period. Additionally, the study aims to monitor the presence of adverse events and adverse drug reactions to determine the safety profile of the treatment. The secondary objectives include:
- Assessment of various lipid parameters during the 12-week treatment period.
- Evaluation of the safety and tolerability of K-924 HD tablets.
Participants
The sponsor did not provide the total number of participants. The study population consists of patients diagnosed with hypercholesterolemia. Eligible individuals include both males and females within specific age ranges. Participants must have an inadequate response to pitavastatin 4 mg and have been receiving certain statins for at least two weeks. A requirement for inclusion is the adherence to a specific diet or exercise regimen for a minimum of four weeks prior to the study. The trial aims to evaluate:
- LDL-C levels as determined by the Friedewald formula following 12 weeks of treatment with K-924 HD.
- The occurrence of adverse events and adverse drug reactions during the 12-week treatment period.
Plans and Procedures
This Phase 3, randomized, double-blind, active-controlled, parallel-group, multicenter trial is designed to evaluate the efficacy and safety of K-924 in participants with hypercholesterolemia who have shown an inadequate response to pitavastatin 4 mg. The study methodology utilizes a comparative approach involving K-924, pitavastatin, and appropriate placebo groups. The primary objective is to assess the percent change from baseline in LDL-C using the Friedewald formula after 12 weeks of treatment, alongside the monitoring of adverse events and adverse drug reactions. The study sequence begins with a screening visit to confirm eligibility based on age, dietary regimen, and specific fasting lipid levels. Following screening, participants will undergo a 12-week treatment period. The clinical assessment includes evaluations at Week 6 and concludes with an end-of-study visit at Week 12. Total participant involvement is estimated to span the 12-week treatment duration.
Treatment
The experimental medication, K-924, is an oral tablet containing a combination of ezetimibe and pitavastatin at a dosage of 14 mg.
The comparator treatment consists of Livazo, which is a 4 mg film-coated tablet of pitavastatin administered orally.
The study utilizes placebo administrations to maintain the double-blind design. This includes a placebo identical to the K-924 tablet without active ingredients, as well as a placebo identical to the comparator drug without active ingredients.
Background therapy involves the administration of 4 mg of pitavastatin via the oral route.
Efficacy
The efficacy of the treatment in participants with hypercholesterolemia will be evaluated based on the primary endpoint of percent change from baseline in low-density lipoprotein cholesterol (LDL-C) calculated using the Friedewald formula at 12 weeks. In instances where triglycerides (TG) are ≥400 mg/dL or the calculated LDL-C is <50 mg/dL, the direct enzymatic method will be utilized to measure LDL-C.
Secondary efficacy assessments include the proportion of participants achieving specific fasting LDL-C goals at week 6 and week 12, categorized by risk levels. The following parameters will be evaluated for changes from baseline and absolute values at weeks 6 and 12:
- HDL-C (direct enzymatic method)
- non-HDL-C
- total cholesterol (TC)
- The ratio of LDL-C (Friedewald formula) to HDL-C and non-HDL-C to HDL-C
Additionally, the change and percent change from baseline in apolipoprotein B (ApoB) will be measured at week 12 as an exploratory measure. Changes in physiological and clinical laboratory test values will also be monitored at each scheduled timepoint.
Inclusion and Exclusion Criteria
Inclusion Criteria
- (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
Exclusion Criteria
- (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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 30 Apr 2026 | 40 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Livazo 4mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 4 | 14 | PRD715490 |
K-924 HD Placebo: The same IMP as test drug but no active ingredients. | Placebo | N/A | — | — | — | N/A |
PITAVASTATIN | Other | — | ORAL | 4 | 12 | SUB21363 |
EU-marketed pitavastatin 4 mg Placebo: The same drug as comparator but no active ingredients | Placebo | N/A | — | — | — | N/A |
K-924 | Test | TABLET | ORAL USE | 14 | 14 | PRD13273818 |