Pemafibrate to Reduce cardiovascular OutcoMes by reducing triglycerides IN patiENts with diabeTes
- Conditions
- heart and vascular diseaseincreased TriGlucerideglyceride (type of fat)100822061001265310003216
- Registration Number
- NL-OMON53131
- Lead Sponsor
- Kowa Research Institute, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 231
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 >= 200mg/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
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-γ
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) <= the
lower limit of normal] 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is the time from randomization to the first<br /><br>occurrence of any component of the clinical composite endpoint of:<br /><br>• Nonfatal MI<br /><br>• Nonfatal ischemic stroke<br /><br>• Coronary revascularization<br /><br>• Cardiovascular death</p><br>
- Secondary Outcome Measures
Name Time Method