Clinical trial NCT04289662: K-924 Phase III Long Term Study
Official title: A Multicenter, Open-label Study to Evaluate 52 Weeks Long Term Efficacy and Safety of K-924 in Patients With Hypercholesterolemia Who Were Treated With Pitavastatin 2 mg or 4 mg.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Kowa Company, Ltd.
Sponsor class: INDUSTRY
First posted: 2020-02-28
Enrollment: 110
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Multicenter, Open-label Study to Evaluate 52 weeks long term Efficacy and Safety of K-924 in Patients with hypercholesterolemia who were treated with pitavastatin 2 mg or 4 mg.


Eligibility criteria: Inclusion Criteria:

1. Patients with hypercholesterolemia had to be age 20 years or older at written informed consent (ICF)
2. Patients who have been on a diet and / or exercise regimen more than 4 weeks before the screening
3. Patients who have been receiving pitavastatin calcium 2 mg / day or pitavastatin calcium 4 mg / day at least 4 weeks prior to the screening
4. Those whose LDL-C (Friedewald formula) at the screening any of the following in the category classification based on Japan Atherosclerosis Society guidelines for prevention Atherosclerotic Cardiovascular Disease 2017

   * Low risk of primary prevention : LDL-C =\> 160 mg/dL
   * Medium risk of primary prevention : LDL-C =\> 140 mg/dL
   * High risk of primary prevention : LDL-C =\> 120 mg/dL
   * Secondary prevention patients with a history of coronary artery disease : LDL-C =\> 100 mg/dL
   * Secondary prevention patients with familial hypercholesterolemia or acute coronary syndrome, or diabetes with other high-risk conditions : LDL-C =\> 70 mg/dL

Exclusion Criteria:

1. Patients with a history of myopathy or rhabdomyolysis due to pitavastatin or ezetimibe
2. Patients with a history of hypersensitivity due to pitavastatin or ezetimibe
3. Patients with severe liver damage (Child Pugh Class B or higher) or biliary obstruction
4. Pregnant women, lactating women, women planning to become pregnant or lactating during the study period, or pregnant women who do not use specific contraceptive methods
5. Patients whose CK is 3 times or more of the upper limit of the reference value at screening
6. Patients whose AST and ALT is 2 times or more of the upper limit of the reference value at screening
7. Patients wiht type 1 diabetes or uncontrolled type 2 diabetes as defined HbA1c 8 % or more at screening
8. Patients with uncontrolled hypertension as defined systolic blood pressure of 160 mmHg or more or diastolic blood pressure of 100 mmHg or more at screening
9. Patients with eGFR of less than 30 mL / min / 1.73 m² at screening or dialysis
10. Patients with heart failure class III or higher according to NYHA cardiac function classification
11. Patients with uncontrolled arrhythmia
12. Patients with uncontrolled metabolic endocrine disease
13. Patients with malignant tumors or who are judged to have a high possibility of relapse
14. Patients who developed acute coronary syndrome or stroke within 12 months before obtaining consent
15. Patients who have collected 200 mL or more within 4 weeks before screening, 400 mL or more of blood within 12 weeks for males or 16 weeks for females, or within 2 weeks for (Plasma component / platelet component)
16. Persons with a history of severe drug allergy (anaphylactic shock, etc.)
17. Patients who need contraindicated drugs during the study period after obtaining consent
18. Patients with TG of 400 mg / dL or more at screening
19. Patients who have LDL apheresis
20. Patients with malabsorption or history, or who have undergone gastrointestinal surgery (excluding appendectomy, hernia treatment, etc.) that may affect absorption.
21. Patients with Alcohol or drug addiction
22. Patients who participate in other clinical trials within 16 weeks prior to study drug administration and who are administered non-placebo investigational drugs, or who participate in other clinical trials concurrently with this study
23. Patients who have received K-924
24. Patients who judged to be inappropriate by the Investigator or Investigator

Primary outcomes:
measure: Efficacy: % change from baseline in LDL-C (Friedewald formula) (mg/dL)
timeFrame: Week 52
Secondary outcomes:
measure: Efficacy: % change or change from baseline in LDL-C (mg/dL)
timeFrame: From baseline upto week 52
measure: Efficacy: % change or change from baseline in non-HDL-C (mg/dL)
timeFrame: From baseline upto week 52
measure: Efficacy: % change or change from baseline in HDL-C (mg/dL)
timeFrame: From baseline upto week 52
measure: Efficacy: % change or change from baseline in Total Cholesterol (mg/dL)
timeFrame: From baseline upto week 52
measure: Efficacy: % change or change from baseline in TG (mg/dL)
timeFrame: From baseline upto week 52
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Chubu Rosai Hospital
city: Aichi
country: Japan
facility: Daido Clinic
city: Fukuoka
country: Japan
facility: Nakamura Cardiovascular Clinic
city: Hiroshima
country: Japan
facility: Nippon Kokan Fukuyama Hospital
city: Hokkaido
country: Japan
facility: Hasegawa Medicine Clinic
city: Hokkaido
country: Japan
facility: Miyanomori Memorial Hospital
city: Hokkaido
country: Japan
facility: Yuri Ono Clinic
city: Kanagawa
country: Japan
facility: Ota General Hospital
city: Nagano
country: Japan
facility: Suwa Red Cross Hospital
city: Osaka
country: Japan
facility: Shiraiwa medical clinic
city: Tokyo
country: Japan
facility: Minamino Cardiovascular Hospital
city: Tokyo
country: Japan
facility: Tokyo Shinagawa Hospital
city: Tokyo
country: Japan
facility: Tokyo-Eki Center-building Clinic
Study officials:
References:
citation: Ako J, Yokote K, Tsujita K, Tanigawa R, Kamei R, Suganami H. Long-term Efficacy and Safety of K-924 Pitavastatin/Ezetimibe Fixed-dose Combination in Patients with Hypercholesterolemia: A Phase III, Multi-center, Open-label Trial. J Atheroscler Thromb. 2024 Mar 1;31(3):288-305. doi: 10.5551/jat.64272. Epub 2023 Sep 16.