Pemafibrate to reduce risk of cardiovascular events in patients with diabetes.
- Conditions
- Reduction of cardiovascular events in patients with Type II DiabetesMedDRA version: 20.0Level: HLTClassification code 10012654Term: Diabetic complications cardiovascularSystem Organ Class: 100000004860Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-003818-26-SK
- Lead Sponsor
- Kowa Research Institute, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 10000
1. Fasting TG = 200 mg/dL (2.26 mmol/L) and < 500 mg/dL (5.65 mmol/L) at Visit 1 (Screening/Enrollment Visit) or Visit 1.1 (Retest)
2. HDL-C = 40 mg/dL (1.03 mmol/L) at Visit 1 (Screening/Enrollment Visit) or Visit 1.1 (Retest)
3. Type 2 diabetes of longer than 12 weeks duration documented in medical records, for example: local laboratory evidence through medical record review of elevated HbA1c (= 6.5% [48 mmol/mol]), elevated plasma glucose (fasting = 126 mg/dL [7.0 mmol/L], 2-hour = 200 mg/dL [11.1 mmol/L] during oral glucose tolerance testing, or random value = 200 mg/dL with classic symptoms, or currently taking medication for treatment of diabetes; AND either
a) Age = 50 years if male or = 55 years if female (primary prevention cohort); OR
b) Age = 18 years and established systemic atherosclerosis (secondary prevention cohort), defined as any 1 of the following:
i. Prior MI or ischemic (non-hemorrhagic) stroke
ii. Coronary angiographic lesion of = 60% stenosis in a major epicardial vessel or = 50% left main stenosis
iii. Asymptomatic carotid disease with = 70% carotid artery stenosis
iv. Symptomatic carotid disease with = 50% carotid artery stenosis
v. Symptomatic lower extremity peripheral artery disease (PAD) (ie, intermittent claudication, rest pain, lower extremity ischemic ulceration, or major amputation with either ankle brachial index = 0.9 or other diagnostic testing [eg, toe-brachial index, angiogram, or other imaging study])
vi. Prior arterial revascularization procedure (including coronary, carotid, or peripheral angioplasty/stenting, bypass, or atherectomy/endarterectomy)
4. In addition, by Visit 1 (Screening/Enrollment Visit), participants must be either:
a) Receiving treatment with a stable dose (ie, for at least 12 weeks) of a qualifying moderate- to high intensity statin (atorvastatin = 40 mg/day, rosuvastatin = 20 mg/day, simvastatin = 40 mg/day*, or pitavastatin 4 mg/day); or
b) Have evidence of LDL-C = 70 mg/dL (1.81 mmol/L) by local laboratory determination within the previous 12 months#, or
c) Statin intolerant+ and have evidence of LDL-C = 100 mg/dL (2.59 mmol/L) by local laboratory determination within the previous 12 months.
* Participants enrolled on simvastatin > 40 mg/day must have been taking and tolerating that dose for at least 12 months.
# If untreated or on stable dosing (ie, for at least 12 weeks) of another lipid-lowering regimen that may include a statin with or without ezetimibe and/or a PCSK9 inhibitor
+ Statin intolerance is defined as: the inability to tolerate at least 2 statins: 1 statin at the lowest daily starting dose (defined as rosuvastatin 5 mg, atorvastatin 10 mg, simvastatin 10 mg, lovastatin 20 mg, pravastatin 40 mg, fluvastatin 40 mg or pitavastatin 2 mg), AND another statin at any dose, due to skeletal muscle-related symptoms, other than those due to strain or trauma, such as pain, aches, weakness, or cramping, that begins or increases during statin therapy and stops when statin therapy is discontinued. Participants not receiving a daily regimen of a statin (e.g., 1-3 times weekly) could also be considered statin intolerant” if they cannot tolerate a cumulative weekly statin dose of 7 times the lowest approved tablet size, and the criteria outlined above are also met.
5. Ability to understand and comply with study procedures and give written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Nu
1. Current or planned use of fibrates or agents with potent peroxisome proliferator activated receptor (PPAR)-a agonist activity (eg, saroglitazar) within 6 weeks (42 days) of Visit 1 (Screening/Enrollment Visit). Note: PPAR-? agonists (eg, glizatones such as pioglitazone and rosiglitazone) are allowed
2. Known sensitivity to PPAR-a agonists or tablet excipients
3. Initiation of, or change in, current TG-lowering therapy within 12 weeks of Visit 1 (if applicable). Note: TG-lowering therapy is defined as niacin > 100 mg/day or dietary supplements or prescription omega-3 fatty acids > 1 g/day
4. Type 1 diabetes mellitus
5.Uncontrolled diabetes mellitus as defined by a HbA1c > 9.5% [80 mmol/mol] at Visit 1 (Screening/Enrollment Visit)
6.Untreated or inadequately treated hypothyroidism [thyroid stimulating hormone (TSH) > 2.0 X the upper limit of normal (ULN) or free thyroxine (T4) = ULN] or hyperthyroidism; controlled thyroid disease (permitted) requires normal TSH and stable therapy for at least 4 weeks
7. Recent CVD event (eg, MI or stroke) within 8 weeks of Visit 2 (Randomization Visit)
8. Recent or planned vascular intervention within 8 weeks of Visit 2
9. New York Heart Association Class IV heart failure (HF)
10. Known homozygous familial hypercholesterolemia (heterozygous is permitted) or familial hypoalphalipoproteinemia
11.Documented previous occurrence of myositis/myopathy
12.Unexplained creatine kinase (CK) > 5 X ULN
13.Liver disease defined as cirrhosis or Child-Pugh class B and C, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 X ULN
14.Biliary obstruction or hyperbilirubinemia (ie, total bilirubin > 2 X ULN, except with a documented diagnosis of Gilbert’s disease)
15.Chronic renal insufficiency, defined by an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or kidney transplant, regardless of renal function
16.Unexplained anemia (hematocrit = 30%)
17.Uncontrolled hypertension (seated systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg) at Visit 2 (Randomization Visit).
18.History of chronic active hepatitis B or hepatitis C, or known infection with HIV; participants with documented hepatitis C resolution after treatment are permitted
19.Active malignancy, except non-melanoma skin cancer or carcinoma in situ of the cervix, within the last 2 years.
20.Prior organ transplant or any condition likely to lead to organ transplantation in the next 5 years
21.Current or anticipated chronic use of cyclosporine, rifampicin, or other inhibitors of organic anion transporting polypeptides (OATP)1B1, or OATP1B3
22.History of alcoholism or unwillingness to limit alcohol intake to < 15 alcoholic beverages (or units) per week or < 5 alcoholic beverages (or units) during a single occasion for men and < 8 alcoholic beverages (or units) per week or < 4 alcoholic beverages (or units) during a single occasion for women during the study period. Note: One alcoholic beverage (unit) is defined as 12 oz. (350 mL) of beer, 5 oz. (150 mL) of wine, or 1.5 oz. (45 mL) of liquor
23.History of hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
24.Women who are pregnant, lactating, planning to be pregnant or lactating during the study period, or WOCP who are not using an acceptable method of contraception
25.A medical condition, other than vascular disease, with l
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method