Diazoxide Choline in Hypertriglyceridemia

A Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Diazoxide Choline in Non-Diabetic Hypertriglyceridemic Subjects

Hypertriglyceridemia affects 30% of the population in the US. Very high level of triglycerides is a known risk factor for pancreatitis. In addition, studies have shown that hypertriglyceridemia is an independent risk factor for cardiovascular disease.

Diazoxide is a KATP channel opener. It has been approved by the FDA as an oral suspension for the treatment of hyperinsulinemic hypoglycemic conditions and as an IV solution for malignant hypertension. Preclinical and clinical studies suggest that diazoxide can be a potential therapeutic agent for hypertriglyceridemia.

Diazoxide choline is a novel, highly crystalline proprietary salt of diazoxide, which has been formulated as a controlled-release tablet suitable for once per day dosing. This current study is designed to assess the effect of diazoxide choline on triglycerides in subjects with baseline hypertriglyceridemia. In addition, the effects on other lipid parameters, glucose and insulin, body weight as well as the safety and tolerability of diazoxide choline will be assessed.

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia
• Intervention / Treatment: Drug: Placebo; Drug: Diazoxide choline

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90057
      • National Research Institute
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Miami Gardens, Florida, United States, 33169
      • Allied Research International/Cetero Research
    • Tampa, Florida, United States, 33606
      • Meridien Research
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Lipid and Diabetes Research Center
  • North Carolina
    • Winston Salem, North Carolina, United States, 27103
      • Piedmont Medical Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Metabolic and Atherosclerosis Research Center (MARC)
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd
    • Marion, Ohio, United States, 43302
      • Frederick C. Smith Clinic
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Tricities Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• triglycerides ≥ 250 mg/dL and < 600 mg/dL
• BMI between 18.5 and 45
• Signed informed consent form

Exclusion Criteria:

• Fasting glucose ≥ 126 mg/dL
• Glycosylated hemoglobin (HbA1c) > 6.5%
• LDL cholesterol > 190 mg/dL
• Known history of type I and II DM
• Known history of type I and III hyperlipidemia
• Weight change > 3 kg between screening and baseline visits
• Pregnancy or intention to become pregnant
• Presence of significant underlying conditions that may interfere with the assessments of the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 4	Drug: Placebo
Experimental: 1; Diazoxide equivalent dose	Drug: Diazoxide choline
Experimental: 2; Diazoxide equivalent dose	Drug: Diazoxide choline
Experimental: 3; Diazoxide equivalent dose	Drug: Diazoxide choline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the effect on triglycerides of repeated doses of Diazoxide Choline Controlled-Release Tablet over a period of 56 days in hypertriglyceridemic subjects	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the effect on other lipid parameters (LDL, HDL, VLDL, and non-HDL cholesterol), insulin, glucose and weight of repeated doses of Diazoxide Choline Controlled-Release Tablet over a period of 56 days in hypertriglyceridemic subjects	8 weeks
To assess the safety and tolerability of repeated doses of Diazoxide Choline Controlled-Release Tablet over a period of 56 days in hypertriglyceridemic subjects	8 weeks

Collaborators and Investigators

• Sponsor: Essentialis, Inc.
• Collaborators: Medpace, Inc.
• Investigators: Principal Investigator: Harold Bays, MD, L-MARC Research Center; Principal Investigator: Philip Toth, MD, Midwest Institute for Clinical Research; Principal Investigator: Michael Koren, MD, Jacksonville Center for Clinical Research; Principal Investigator: Alan Forker, MD, St. Luke's Lipid and Diabetes Research Center; Principal Investigator: Cynthia Huffman, MD, Meridien Research; Principal Investigator: Andrew Lewin, MD, National Research Institute; Principal Investigator: Thomas Littlejohn, MD, Piedmont Medical Research Associates; Principal Investigator: David Morin, MD, Tricities Medical Research; Principal Investigator: Evan Stein, MD, Metabolic and Atherosclerosis Research Center (MARC); Principal Investigator: Craig Thompson, MD, Frederick C. Smith Clinic; Principal Investigator: Glibert Weiner, MD, Allied Research International/Cetero Research

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: June 10, 2008
• First Submitted That Met QC Criteria: June 10, 2008
• First Posted (Estimate): June 12, 2008

Study Record Updates

• Last Update Posted (Estimate): November 7, 2010
• Last Update Submitted That Met QC Criteria: November 4, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertriglyceridemia; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Nootropic Agents; Lipotropic Agents; Diazoxide; Choline
• Other Study ID Numbers: PC007