Reduction of cardiovascular events in patients with Type II Diabetes MedDRA version: 20.0 Level: HLT Classification code 10012654 Term: Diabetic complications cardiovascular System Organ Class: 100000004860
Conditions
Interventions
Product Name: Pemafibrate
Product Code: K-877
Pharmaceutical Form: Tablet
INN or Proposed INN: Pemafibrate
CAS Number: 848259–27–8
Current Sponsor code: K-877
Other descriptive name: K-877
Concentrati
Sponsors
Kowa Research Institute, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Fasting TG = 200 mg/dL (2.26 mmol/L) and 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
Exclusion criteria
Exclusion criteria: 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) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary scientific aim of the PROMINENT study is to assess whether treatment with the selective peroxisome proliferator activated receptor modulator alpha (SPPARM-a), pemafibrate, will prevent myocardial infarction (MI), ischemic stroke, coronary revascularization, and cardiovascular (CV) death in adults with type 2 diabetes (T2D) who have elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels and are at high risk for future CV events. Specifically, the primary objective of the study is to determine whether pemafibrate administered at a dose of 0.2 mg twice daily will delay the time to first occurrence of any component of the clinical composite endpoint of: •nonfatal MI; •nonfatal ischemic stroke; •coronary revascularization; or •CV death.;Secondary Objective: The secondary scientific aim of this study is to investigate 1) the efficacy (time to first occurrence) of a number of secondary CV and diabetes-related vascular and nonvascular endpoints in the study population, and 2) the efficacy (as measured by the percent change from baseline) for a number of lipid measures.;Primary end point(s): The primary efficacy endpoint is the time from randomization to the first occurrence of any component of the clinical composite endpoint of: •Nonfatal MI •Nonfatal ischemic stroke •Coronary revascularization •Cardiovascular death;Timepoint(s) of evaluation of this end point: Variable as event driven | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The group A (clinical) endpoints are time to first occurrence of: - The 4-component composite endpoint of non-fatal MI, non-fatal ischemic stroke, hospitalization for unstable angina requiring unplanned coronary revascularization or cardiovascular death - The 3-component composite endpoint of non-fatal MI, non-fatal ischemic stroke, or cardiovascular death - Any component of the primary endpoint or hospitalization for HF - Any component of the primary endpoint or all-cause mortality - Any new or worsening PAD, defined as incidence of lower extremity revascularization, 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) - Time of first occurrence of individual endpoints and an analysis of total events (evaluating time to occurrence of the first and all recurrent nonfatal MI, non-fatal ischemic stroke, coronary revascularization, or cardiovascular death). - Additionally, as a prespecified secondary analysis, evidence of any genetic effect modification that may relate to pemafibrate and incident cardiovascular events will be evaluated. In particular, whether the effect of pemafibrate as compared with placebo on cardiovascular events differs according to known genetic polymorphisms in the PPARA gene (such as, but not limited to rs6008845), will be assessed. The group B (lipid) endpoints are: • The change from Screening/Enrollment Visit (Visit 1) to Month 4 Visit (Visit 5) for the following lipid biomarkers: TC, TG, HDL-C, non-HDL-C (calculated), VLDL-C (calculated), ApoA1, ApoC3, and ApoE; and • The change from Randomization Visit (Visit 2) to Month 6 Visit (Visit 6) for non-fasting remnant cholesterol * VLDL-C will be calculated as TC minus HDL-C minus LDL-C, where LDLC is measured by a direct homogenous method.;Timepoint(s) of evaluation of this end point: Variable with excepti | — |
Countries
Argentina, Brazil, Bulgaria, Canada, Colombia, Czechia, Czech Republic, Denmark, France, Germany, Hungary, India, Israel, Japan, Mexico, Netherlands, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactDavid Sojka
IQVIA
Outcome results
None listed