A 12-Week, Phase 2 Study of Gemcabene in Hypercholesterolemia Patients on Stable Moderate and High-Intensity Statins
Condition: Hypercholesteremia
MeSH terms: Hypercholesterolemia
Intervention: Gemcabene; Placebo
Intervention description: Two 300 mg tablets and 1 placebo tablet administered orally, once daily for 12 weeks.; Three placebo tablets administered orally once daily for 12 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 105.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: LDL-C; Lipid Regulator

Summary:

      The purpose of this study was to assess the efficacy, safety, and tolerability of multiple
      doses of gemcabene 600 mg QD compared to placebo in patients with hypercholesterolemia not
      adequately controlled on high-intensity or moderate-intensity stable statin therapy. Patients
      with HeFH, ASCVD, or otherwise uncontrolled, may be included with baseline LDL-C value ≥ 100
      mg/dL. Subjects were randomized 1:1 to gemcabene 600 mg once daily (QD) or placebo.
    

Eligibility criteria:

        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.