A 12-Week, Phase 2 Study of Gemcabene in Hypercholesterolemia Patients on Stable Moderate and High-Intensity Statins (ROYAL-1)

This is an interventional treatment trial for Hypercholesteremia focused on measuring LDL-C, Lipid Regulator Read More

1. Provision of written and signed informed consent (by subject or legal guardian) prior to any study-specific procedures;
2. Male or female (neither pregnant or lactating) ≥ 18 years of age at the time of consent;
3. Currently on a stable, low-fat, low-cholesterol diet in combination with allowed statin doses as described in Table 1, with or without ezetimibe 10 mg QD for at least 12 weeks prior to the Screening Visit;
4. Fasting LDL-C value ≥ 100 mg/dL (2.59 mmol/L) at the Screening Visit;
5. Physical examination, including vital signs, that is within normal limits or clinically acceptable to the Investigator;
6. Weight ≥ 50 kg; with a body mass index (BMI) ≤ 45 kg/m2
7. Subjects with Type 2 diabetes who take anti-hyperglycemic agents must be on a stable regimen for at least 3 months, with no planned changes in medications for the study duration.

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.