Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes (PROMINENT)

Phase 3TerminatedNCT03071692

Kowa Research Institute, Inc.10,544 enrolled

Overview

The primary objective of the study is to determine whether pemafibrate administered twice daily will delay the time to first occurrence of any component of the clinical composite endpoint of: * nonfatal Myocardial Infarction (MI) * nonfatal ischemic stroke * coronary revascularization; or * Cardio Vascular (CV) death.

A multi-regional clinical trial with participating sites in the following countries. India is being conducted under a previous protocol version due to regulatory requirements. * Argentina * Brazil * Bulgaria * Canada * Colombia * Czech Republic * Denmark * France * Germany * Hungary * India * Israel * Japan * Mexico * Netherlands * Poland * Romania * Russian Federation * Slovakia * South Africa * Spain * Ukraine * United Kingdom * United States

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

10,544

Conditions

Type2 Diabetes Dyslipidemia

Interventions

K-877DRUG

0.2mg tablet

PlaceboDRUG

K-877 matching placebo tablet

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 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 1. Age ≥ 50 years if male or ≥ 55 years if female (primary prevention cohort); OR 2. 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 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) Exclusion Criteria: 1. Current or planned use of fibrates or agents with PPAR-α 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-α 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

Locations (888)

Outcomes

Primary Outcomes

Number of Participants With First Occurrence of 4-component Composite Primary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Coronary Revascularization, or CV Death)

Number of participants experiencing their first occurrence of any component of the 4-component composite primary endpoint, which includes nonfatal myocardial infarction (MI), nonfatal ischemic stroke, coronary revascularization, or cardiovascular (CV) death. Each participant is counted only once, regardless of any subsequent events.

Time frame: From Baseline to a Median of 3.3 Years

Secondary Outcomes

Number of Participants With First Occurrence of the 4-component Composite Secondary Endpoint (Nonfatal MI, Nonfatal Ischemic Stroke, Hospitalization for Unstable Angina Requiring Unplanned Coronary Revascularization, or CV Death)

The 4-component composite secondary endpoints events are nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for unstable angina requiring unplanned coronary revascularization, or cardiovascular death

Time frame: From Baseline to a Median of 3.3 Years

Number of Participants With First Occurrence of the 3-component Composite Endpoint (Nonfatal Myocardial Infarction, Nonfatal Ischemic Stroke, or Cardiovascular Death)

Number of Participants with First Occurrence of Composite Cardiovascular Events (nonfatal myocardial infarction, nonfatal ischemic stroke, or cardiovascular death)

Time frame: From Baseline to a Median of 3.3 Years

Number of Participants With First Occurrence of Any Component of the Primary Endpoint or Hospitalization for Heart Failure

Event is the first occurrence of any component of the composite endpoint of nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, cardiovascular death, or hospitalization for heart failure

Time frame: From Baseline to a Median of 3.3 Years

Data from ClinicalTrials.gov

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Synexus Clinical Research US, Inc.

Birmingham, Alabama, United States

University of Alabama at Birmingham

Birmingham, Alabama, United States

VA Medical Center - Birmingham

Birmingham, Alabama, United States

Alabama Clinical Therapeutics, LLC

Birmingham, Alabama, United States

Fundamental Research, LLC

Gulf Shores, Alabama, United States

Mobile Heart Specialists, PC

Mobile, Alabama, United States

Terence T. Hart, MD

Tuscumbia, Alabama, United States

Synexus Clinical Research US, Inc.

Chandler, Arizona, United States

Synexus Clinical Research US, Inc.

Mesa, Arizona, United States

Arizona Arthritis & Rheumatology Research, PLLC

Peoria, Arizona, United States

...and 878 more locations

Number of Participants With Occurrence of Any Component of the Primary Endpoint or All-Cause Mortality

Time frame: From Baseline to a Median of 3.3 Years

Total Number of Events of the 4-component Composite Primary Endpoint

Total number of events for the 4-component composite primary endpoint, counting all occurrences, including multiple events in the same participant. The endpoint events include nonfatal myocardial infarction (MI), nonfatal ischemic stroke, coronary revascularization, and cardiovascular (CV) death.

Time frame: From Baseline to a Median of 3.3 Years

Number of Participants With First Occurrence of Any New or Worsening Peripheral Artery Disease (PAD)

Any new or worsening Peripheral artery disease (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 frame: From Baseline to a Median of 3.3 Years

Number of Participants With First Occurrence of Nonfatal Myocardial Infarction

Time frame: From Baseline to a Median of 3.3 Years

Number of Participants With First Occurrence of Nonfatal Ischemic Stroke

Time frame: From Baseline to a Median of 3.3 Years

Number of Participants With First Occurrence of Coronary Revascularization

Time frame: From Baseline to a Median of 3.3 Years

Number of Participants With First Occurrence of Cardiovascular Death

Time frame: From Baseline to a Median of 3.3 Years

Number of Participants With First Occurrence of the 4-component Composite Endpoint by PPAR-α Gene Variant Subgroup (TT, CT, CC)

Number of participants experiencing their first occurrence of any component of the 4-component composite primary endpoint (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or cardiovascular death), reported as a subgroup analysis by PPAR-α gene variants (TT, CT, CC).

Time frame: From Baseline to a Median of 3.3 Years

Percent Change From Baseline to Month 4 for Total Cholesterol (TC)

Time frame: Baseline to Month 4

Percent Change From Baseline to Month 4 for Fasting Triglycerides

Time frame: Baseline to 4 Months

Percent Change From Baseline to Month 4 for HDL - Cholesterol (HDL-C)

Time frame: Baseline to Month 4

Percent Change From Baseline to Month 4 for Calculated Non-HDL Cholesterol (Non-HDL-C)

Time frame: Baseline to Month 4

Percent Change From Baseline to Month 4 for Calculated VLDL Cholesterol

Time frame: Baseline to Month 4

Percent Change From Baseline to Month 4 for Apolipoprotein A1 (ApoA1)

Time frame: Baseline to Month 4

Percent Change From Baseline to Month 4 for Apolipoprotein CIII (ApoC3)

Time frame: Baseline to Month 4

Percent Change From Baseline to Month 4 for Apolipoprotein E (ApoE)

Time frame: Baseline to Month 4

Percent Change From Baseline to Month 6 for Non-fasting Remnant Cholesterol

Time frame: Baseline to Month 6