Diazoxide Choline Controlled-Release Tablet (DCCR) for Very High Triglycerides

Study Overview
=================
Brief Summary
-----------------
The hypothesis of this study is that DCCR is effective as both monotherapy and in combination with a statin in lowering triglycerides in subjects with very high triglycerides

Detailed Description
-----------------
Very high triglyceride is a risk for pancreatitis. Studies have shown Diazoxide Choline has the potential to effectively lower triglycerides in patients with very high triglycerides.

Official Title
-----------------
A Multi-Center, Randomized, Double-Blind, Placebo- and Active-Controlled Study Assessing the Efficacy, Safety and Tolerability of Diazoxide Choline Controlled-Release Tablet (DCCR) in Subjects Without Diabetes Mellitus Having Very High Fasting Triglyceride Levels, With Double-Blind Active-Controlled Extension Assessing Safety and Tolerability

Conditions
-----------------
Hypertriglyceridemia

Intervention / Treatment
-----------------
* Drug: 290 mg DCCR
* Drug: 435 mg DCCR
* Drug: 135 mg fenofibric acid
* Drug: Placebo
* Drug: atorvastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Fasting triglycerides Difference between Visit 3 (7 days prior to Baseline Visit) and Visit 4 (3 days prior to Baseline Visit) ≤ 60% (compared to the higher value of Visit 3 or Visit 4) Run-in Triglycerides* ≥ 500 mg/dL and < 1500 mg/dL *Run-in Triglyceride is defined as the average fasting triglycerides for Visit 3 (7 days prior to Baseline Visit) and Visit 4 (3 days prior to Baseline Visit). Statin use Either Statin-naive - Must not be on statin at Screening and remaining as such during the Run-in/Washout Period and throughout the study Or Statin-treated Must be receiving a stable and effective dose of statin for ≥ 3 months without significant side effects or intolerance prior to Screening Must be willing to switch to 20 mg atorvastatin at the start of the Run-in/Washout Period and continue throughout the study Medication washout All subjects must be willing to undergo washout of all other lipid-lowering medications Fasting LDL cholesterol ≤ l60 mg/dL at both Screening Visit and Visit 4 Glycemic status Fasting glucose < 126 mg/dL at Screening Visit HbA1c < 6.5% at Screening Visit EXCLUSION CRITERIA: Medications: recent, current, anticipated Administration of investigational drugs within 1 month prior to Screening Visit Thyroid hormones or preparations within 1 month prior to Screening Visit (except in subjects on stable dose of replacement therapy for at least 1 month) Thiazide diuretics within 2 weeks prior to Screening Visit Discontinuation of beta-blockers within 1 month prior to Screening Visit or planned discontinuation of beta-blocker therapy Anticipated requirement for use of prohibited concomitant medications History of allergic reaction or significant intolerance to: Diazoxide Thiazides Sulfonamides Fenofibrate or fenofibric acid derivatives Lifestyle changes • Subjects intending to change exercise habits, quit smoking and/or quit alcohol use during the initial 12-week Placebo-Controlled Treatment Period of the study Specific diagnoses, medical conditions and history Known type I or III hyperlipidemia Known type 1 DM Known type 2 DM Any other clinically significant endocrine, cardiovascular, pulmonary, neurological, psychiatric, hepatic, gastrointestinal, hematological, renal, or dermatological disease interfering with the assessments of the study medications, according to the Investigator Specific laboratory test results • Any relevant biochemical abnormality interfering with the assessments of the study medications

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 290 mg DCCR<br> | Drug: 290 mg DCCR<br>* 290 mg diazoxide choline<br>Drug: Placebo<br>* Placebos matching each of 2 doses of DCCR and 135 mg fenofibric acid<br>* Other names: Placebos matching DCCR and fenofibric acid;Drug: atorvastatin<br>* 20 mg atorvastatin<br>* Other names: 20 mg atorvastatin;|
| Experimental: 435 mg DCCR<br> | Drug: 435 mg DCCR<br>* 435 mg diazoxide choline<br>Drug: Placebo<br>* Placebos matching each of 2 doses of DCCR and 135 mg fenofibric acid<br>* Other names: Placebos matching DCCR and fenofibric acid;Drug: atorvastatin<br>* 20 mg atorvastatin<br>* Other names: 20 mg atorvastatin;|
| Active Comparator: 135 mg fenobric acid<br> | Drug: 135 mg fenofibric acid<br>* 135 mg fenofibric acid<br>* Other names: 135 mg fenobric acid;Drug: Placebo<br>* Placebos matching each of 2 doses of DCCR and 135 mg fenofibric acid<br>* Other names: Placebos matching DCCR and fenofibric acid;Drug: atorvastatin<br>* 20 mg atorvastatin<br>* Other names: 20 mg atorvastatin;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebos matching each of 2 doses of DCCR and 135 mg fenofibric acid<br>* Other names: Placebos matching DCCR and fenofibric acid;Drug: atorvastatin<br>* 20 mg atorvastatin<br>* Other names: 20 mg atorvastatin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of DCCR on triglycerides in subjects without diabetes mellitus who have very high triglycerides over a period of 84 days |  | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effects of DCCR on Apo B and non-HDL in subjects without diabetes mellitus who have very high triglycerides over a period of 84 days |  | 84 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hypertriglyceridemia