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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kowa Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

14 May 2026 → ongoing

Decision date (initial)

2026-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Kowa Company, Ltd.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

- To assess LDL-C (Friedewald formula) of treatment with K-924 HD for 12 weeks in participants with hypercholesterolemia with inadequate response to EU-marketed pitavastatin 4mg
- To assess presence or absence of AEs and ADRs of treatment with K-924 HD for 12 weeks in participants with hypercholesterolemia with inadequate response to EU-marketed pitavastatin 4 mg

Secondary objectives 2

1. - To assess lipid parameters of treatment with K-924 HD tablets for 12 weeks in participants with hypercholesterolemia with inadequate response to EU-marketed pitavastatin 4mg
2. - To assess the safety and tolerability of treatment with K-924 HD tablets for 12 weeks in participants with hypercholesterolemia with inadequate response to EU-marketed pitavastatin 4mg

Conditions and MedDRA coding

Hypercholesterolemia

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000030-PIP86-73, EMEA-000031-PIP09-31

Plan to share IPD

No

IPD plan description

The anonymized individual participant data (IPD) from this clinical trial is planned to be used for the purposes required for the marketing authorization application (MAA) to EMA. At present, there are no specific plans to share the IPD from this trial with external organization, or researchers for other purposes.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. (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 2

1. (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.
2. (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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percent change from baseline in LDL-C (Friedewald formula) at 12 weeks of treatment Note: When TG is ≥400 mg/dL (4.5 mmol/L) or calculated LDL-C (Friedewald formula) is <50 mg/dL (1.3 mmol/L), LDL-C (Friedewald formula) is replaced by LDL-C (direct enzymatic method).
2. Presence or absence of AEs and ADRs after the administration of IMP

Secondary endpoints 5

1. 1. Presence or absence of participants achieving LDL-C goals at Week 6 and 12 LDL-C goals - Low or moderate risk: fasting LDL-C of <100 mg/dL (<2.6 mmol) - High risk: fasting LDL-C of <70 mg/dL (<1.8 mmol) - Very high risk: fasting LDL-C of <55 mg/dL (<1.4 mmol)
2. 2. Percent change from baseline in LDL-C (direct enzymatic method), HDL-C (direct enzymatic method), non-HDLC, TC, TG, LDL-C (Friedewald formula)/HDL-C and non-HDLC/HDL-C at Week 6 and 12
3. 3. Values, change and percent change from baseline in fasting LDL-C (Friedewald formula), LDL-C (direct enzymatic method), HDL-C (direct enzymatic method), non-HDL-C, TC, TG, LDL-C (Friedewald formula)/HDL-C and non-HDLC/ HDL-C at Week 6 and 12
4. 4. Change and percent change from baseline in ApoB at Week 12 Note: When TG is ≥400 mg/dL (4.5 mmol/L) or calculated LDL-C (Friedewald formula) is <50 mg/dL (1.3 mmol/L), LDL-C (Friedewald formula) is replaced by LDL-C (direct enzymatic method). Regarding Apo B, due to the nature of the examination, it will be treated as an exploratory measure.
5. Measurement values and changes from baseline of physiological and clinical laboratory test values at each timepoint

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kowa Co. Ltd.

Sponsor organisation

Kowa Co. Ltd.

Address

3 Chome 6-29 Nishiki, Naka Ku Naka Ku

City

Nagoya

Postcode

460-8625

Country

Japan

Scientific contact point

Organisation

Kowa Co. Ltd.

Contact name

Noboru Kaneta

Public contact point

Organisation

Kowa Co. Ltd.

Contact name

Noboru Kaneta

Third parties 4

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications