A 12-Week, Phase 2 Study of Gemcabene in Hypercholesterolemia Patients on Stable Moderate and High-Intensity Statins

Exclusion Criteria

• •1. Abnormal liver function test at the Pre-Screening or Screening Visit (AST or ALT) \> 2x ULN (upper limit of normal), total bilirubin \> 1.5x ULN, or alkaline phosphate \> 2x ULN based on appropriate age and gender normal values. Subjects with bilirubin \> 1.5x ULN and a history of Gilbert's syndrome may be included; reflexive direct bilirubin testing will be used to confirm Gilbert's syndrome;
• •2. Moderate (Grade B) or severe (Grade C) chronic hepatic impairment according to the Child-Pugh classification;
• •3. Active liver disease (e.g. cirrhosis, alcoholic liver disease, hepatitis B, hepatitis C, autoimmune hepatitis, liver failure, liver cancer), history of liver transplant, known diagnosis of HIV or AIDS;
• •4. Triglyceride value ≥ 500 mg/dL at the Pre-Screening Visit or the Screening Visit;
• •5. Moderate to severe renal insufficiency define as an estimated GFR \< 60mL/min/1.73m (calculated using the Chronic Kidney Disease Epidemiology Collaboration equation) at the Pre-Screening Visit or Screening Visit;
• •6. Abnormal urinalysis (proteinuria greater than trace or any male or non-menstruating female with greater than trace hematuria) confirmed by reflexive urine protein:creatinine ration testing;
• •7. Uncontrolled thyroid disease; hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) below the lower limit of normal or \> 1.5x ULN, respectively, based on results from the Pre-Screening Visit or the Screening Visit. If controlled, treatment should be stable for at least 3 months prior to Screening;
• •8. Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (hemoglobin A1c value \> 8.5% based on results from the Pre-Screening or Screening Visit, or taking a thiazolidinedione (i.e. pioglitazone or rosiglitazone);
• •9. New York Heart Association Class III or IV heart failure;
• •10. Myocardial infarction, severe or unstable angina pectoris, coronary angioplasty, coronary artery bypass graft, or other major cardiovascular events resulting in hospitalization within 3 months of the Screening Visit. Subjects with adequately treated stable angina, per Investigator assessment, may be included;
• •11. Uncontrolled cardiac arrhythmia or prolonged QT on the Screening Visit or Day 1 prior to dosing ECG (QTcF \> 450 msec for men and \> 470 msec for women) or known family history of prolonged QT or unexplained sudden cardiac death;
• •12. Uncontrolled hypertension, defined as sitting systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg, and confirmed by repeat measurement;
• •13. Currently receiving cancer treatments or, in the Investigator's opinion, at risk of relapse for recent cancer;
• •14. Inadequate wash-out of a PCSK9 inhibitor (8 weeks prior to the Screening Visit), a fibrate lipid-regulating agent (6 weeks prior to the Screening Visit), niacins (4 weeks prior to the Screening Visit), or other lipid-regulating therapies such as bile acid sequestrants (4 weeks prior to the Screening Visit);
• •15. Hypersensitivity to or a history of significant adverse reactions to any fibrate lipid-regulating agent;
• •16. Use of any excluded medications or supplements (e.g. potent cytochrome P450 \[CYP\] 3A4 inhibitors as described in Appendix D;
• •17. History of drug or alcohol abuse within the past year or inability to comply with protocol requirements, including subjects restrictions (see Section 5.6.3);
• •18. Previously treated with gemcabene (CI-1027), participation in another clinical study of an investigational agent or device concurrently or within 1 month prior the Screening Visit, or use of an investigational agent within 1 month or 5 half-lives (if known), whichever is longer, prior to the Screening Visit;
• •19. Any other finding which, in the opinion of the Investigator, would compromise the subject's safety or participation in the study.