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

Kowa

Status and phase: Terminated; Phase 3

Conditions: Type2 Diabetes; Dyslipidemia

Treatments: Drug: K-877; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03071692

K-877-302

Details and patient eligibility

About

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.

Full 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

Enrollment: 10,544 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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10,544 participants in 2 patient groups, including a placebo group

Treatment Group

Experimental group

Description:

K-877 (pemafibrate) tablet twice daily.

Treatment:

Drug: K-877

Control Group

Placebo Comparator group

Description:

Matching K-877 placebo tablet twice daily.

Treatment:

Drug: Placebo