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

Phase 3

Terminated

• Conditions: Type2 Diabetes; Dyslipidemia
• Interventions: Drug: Placebo; Drug: K-877

• Registration Number: NCT03071692
• Lead Sponsor: Kowa Research Institute, Inc.

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2017-02-23
• Study First Submitted QC: 2017-03-01
• Study First Posted: 2017-03-07
• Study Start: 2017-03-23
• Primary Completion: 2022-07-27
• Study Completion: 2022-07-27
• Status Verified: 2023-07
• Disposition First Submitted: 2023-07-11
• Last Update Submitted: 2023-07-11
• Disposition First Posted: 2023-07-13
• Last Update Posted: 2023-07-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10544

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Placebo	Matching K-877 placebo tablet twice daily.
Treatment Group	K-877	K-877 (pemafibrate) tablet twice daily.

Primary Outcome Measures

Name	Time	Method
Number of patients with first occurrence of nonfatal MI, nonfatal ischemic stroke, coronary revascularization, or CV death.	Through study completion, an average of 4 years

Secondary Outcome Measures

Name	Time	Method
Time to first occurrence of any component of the primary endpoint or hospitalization for Heart failure (HF)	Through study completion, an average of 4 years
Time to first occurrence of any component of the primary endpoint or all-cause mortality	Through study completion, an average of 4 years
Time to first occurrence of any new or worsening Peripheral artery disease (PAD)	Through study completion, an average of 4 years	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 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	Through study completion, an average of 4 years
Time to first occurrence of the 3-component composite endpoint of non-fatal MI, non-fatal ischemic stroke, or cardiovascular death	Through study completion, an average of 4 years
Lipid Endpoints	Week -3 to Month 4 (Visit 1 to Visit 5)	The change from Screening/Enrollment Visit (Visit 1) to Month 4 Visit (Visit 5) for the following lipid biomarkers: Total cholesterol (TC), Triglyceride(s) (TG), High-density lipoprotein cholesterol (HDL-C), non-HDL-C (calculated), Very low-density lipoprotein cholesterol (VLDL-C) (calculated), ApoA1, ApoC3, and ApoE
Nonfasting Remnant Cholesterol Endpoint	Week 0 to Month 6 (Visit 2 to Visit 6)	The change from Randomization Visit (Visit 2) to Month 6 Visit (Visit 6) for nonfasting remnant cholesterol
Time of first occurrence of individual endpoints and an analysis of total events	Through study completion, an average of 4 years	(evaluating time to occurrence of the first and all recurrent non-fatal MI, non-fatal ischemic stroke, coronary revascularization, or cardiovascular death).
Incidence of cardiovascular events	Up to 4 Years	Effect of pemafibrate vs placebo on cardiovascular events compared to known genetic polymorphisms in the PPARA gene

Trial Locations

Locations (863)

Synexus Clinical Research US, Inc.; 🇺🇸 Dallas, Texas, 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

Arizona Arthritis & Rheumatology Research, PLLC; 🇺🇸 Peoria, Arizona, United States

Phoenix Veterans Adminstration Health Care System; 🇺🇸 Phoenix, Arizona, United States

Clinical Research Institute of Arizona, LLC; 🇺🇸 Surprise, Arizona, United States

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