A Post-Marketing Clinical Trial of Pemafibrate in Patients ｗith Hypercholesterolemia and Inadequate Response to Statins

Official title

A Post-Marketing Clinical Trial of Pemafibrate in Patients With Hypercholesterolemia and Inadequate Response to Statins-Multicenter, Placebo Controlled, Randomized, Double Blind, Parallel Group Controlled Trial

Overview

To investigate the efficacy and safety of Pemafibrate 0.2 mg/day or 0.4 mg/day for 12 weeks in patients with hypercholesterolemia and inadequate response to statins, using placebo as a control.

Interventions

• Drug Pemafibrate 0.2 mg/day
  Administered orally once daily
• Drug Pemafibrate 0.4 mg/day
  Administered orally once daily
• Drug Placebo
  Administered orally once daily

Primary outcome measures

• Percentage change from baseline in LDL-C (direct) [Time frame: 4, 8, and 12 weeks after administration]

Secondary outcome measures (2)

• Achievement of lipid management targets based on the mean LDL-C (direct) values [Time frame: 4, 8, and 12 weeks after administration]
• Percentage change from baseline in LDL-C(Friedewald formula), HDL-C(direct), non-HDL-C, TC, TG [Time frame: 4, 8, and 12 weeks after administration]

Eligibility criteria

Inclusion Criteria:Patients who meet all the following criteria shall be eligible for the clinical trial.

• Patients with hypercholesterolemia aged 18 years or older at the time of obtaining written informed consent
• Patients who have taken statins at a fixed dose and regimen within the approved dose range for at least four weeks prior to the first screening assessment.
• Patients who have received stable dietary and/or exercise therapy for at least 12 weeks prior to the first screening assessment.
• Patients with the fasting serum TG < 150 mg/dL on two consecutive occasions at screening
• Patients who apply any of the following risk category with LDL-C level (direct) based on JAS2022 on two consecutive occasions at screening

• Low risk for primary prevention: LDL-C >=160 mg/dL
• Intermediate risk for primary prevention: LDL-C >=140 mg/dL
• High risk for primary prevention: LDL-C>=120 mg/dL or 100 mg/dL\*
• Secondary prevention: LDL-C>=100 mg/dL
• Familial hypercholesterolemia (heterozygous): LDL-C>=100 mg/dL

• For patients with diabetes, those with peripheral artery disease (PAD), microvascular complications (retinopathy, nephropathy, neuropathy), or current smoking are included if LDL-C>=100 mg/dL.

Exclusion Criteria:Patients who meet any of the following criteria will be excluded from the clinical trial.

• Patients who require administration of prohibited drugs during the post-marketing clinical trial period after written informed consent
• Patients with type 1 diabetes and uncontrolled type 2 diabetes \[HbA1c(NGSP) >= 10.0 % at Screening\]
• Patients whose LDL-C level changed by more than +20% or -20% in the second screening test compared to the the first.
• Patients with uncontrolled thyroid disease
• Patients who are undergoing or are scheduled to undergo LDL apheresis
• Patients with cirrhosis or those with biliary obstruction
• Patients with gallstones
• Patients with familial hypercholesterolemia (homozygotes)
• Patients with impaired renal function (eGFR < 30 mL/min/1.73 m2 at screening)
• Patients with uncontrolled hypertension (SBP >= 160 mmHg or DBP >= 100 mmHg) at screening
• Patients with AST and ALT levels three times or greater than the upper limit of normal at screening
• Patients with CK levels at least three times the upper limit of normal at screening
• Patients with any of the following experiences within 3 months prior to informed consent: myocardial infarction, severe or unstable angina pectoris, coronary angioplasty, coronary artery bypass surgery, stroke, transient ischemic attack, symptomatic carotid artery stenosis, symptomatic peripheral arterial disease, abdominal aortic aneurysm, uncontrolled severe arrhythmia and decompensated heart failure
• Patients who plan to undergo PCI, CABG, carotid artery or peripheral revascularization
• Patients with heart failure class III or higher according to NYHA cardiac function classification
• Patients with malignant tumor or those who are judged to have a high risk of recurrence
• Patients with a history of myopathy or rhabdomyolysis due to pemafibrate
• Patients with a history of hypersensitivity due to pemafibrate
• Patients with a history of serious drug allergies (anaphylactic shock, etc.)
• Pregnant women, lactating women, women planning to become pregnant or lactating during the study period, or pregnant women of childbearing potential\*2 who do not use specific contraceptive methods\*1
• Patients who have undergone whole blood donation of 400 mL or more within 16 weeks, or 200 mL or more within 4 weeks, or component donation (plasma or platelet donation) within 2 weeks prior to screening.
• Patients with alcoholics or drug addicts
• Patients who participated in other clinical trials of a drug with new active ingredients within 16 weeks or a drug with an approved active ingredients within 12 weeks prior to administration and received an investigational drug other than placebo,or those who will participate in other clinical trials at the same time as the clinical trial
• Patients who are considered inappropriate for participation in this study by the investigator, etc

• 1 Acceptable contraceptive methods: Oral hormonal contraceptives (combination pills containing progestin and estrogen), intrauterine devices, intrauterine hormonal delivery systems, abstinence
• 2 Woman of childbearing potential refers to a woman who is physiologically capable of becoming pregnant with a male partner who has not undergone contraception. However, it does not apply if the investigator confirms that any of the following criteria is met.

• Patients with hysterectomy or tubal ligation before informed consent
• Post-menopausal women (those who have passed more than 1 year since their last menstrual period without other medical reasons).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Japan · 10 centers

• NTT Medical Center Sapporo — Hokkaido
• Ami Higashi Clinic — Ibaraki
• Olive Takamatsu Medical Clinic — Kagawa
• Medical Corporation Shintokai Yokohama Minoru Clinic — Kanagawa
• Medical Corporation Heishinkai OCROM Clinic — Osaka
• Hirose Clinic — Saitama
• Medical Corporation Yukeikai Asano Internal Medicine Clinic — Saitama
• Medical Corporation Asbo Tokyo Asbo Clinic — Tokyo
• … and 2 more centers

Identifiers

NCT: NCT07634484 · PALT03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗