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

A 12-Week, Phase 2 Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy, Safety and Tolerability of Gemcabene in Subjects With Hypercholesterolemia Not Adequately Controlled on High-Intensity or Moderate-Intensity Stable Statin Therapy

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesteremia
• Intervention / Treatment: Drug: Placebo; Drug: Gemcabene

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates, Inc.
  • California
    • Beverly Hills, California, United States, 90211
      • Westside Medical Associates of Los Angeles
    • Huntington Park, California, United States, 90255
      • National Research Institute
    • Los Angeles, California, United States, 90057
      • National Research Institute
  • Florida
    • Atlantis, Florida, United States, 33462
      • Atlantic Clinical Research Collaborative- Cardiology
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Maitland, Florida, United States, 32751
      • Meridien Research, Inc.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Tampa, Florida, United States, 33626
      • Varkey Medical
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Evanston Premier Healthcare Research, LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC
  • New York
    • New Windsor, New York, United States, 12553
      • Mid-Hudson Medical Research
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Sentral Clinical Research Services
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research Group, Ltd.
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd.
  • Pennsylvania
    • Lansdale, Pennsylvania, United States, 19446
      • Green and Seidner Family Practice Associates
  • Texas
    • Houston, Texas, United States, 77027
      • Associates in Medicine
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Grup
    • Sugar Land, Texas, United States, 77479
      • Sugar Lakes Family Practice
  • Virginia
    • Richmond, Virginia, United States
      • National Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants on stable statin therapy received matching placebo orally, once daily for 12 weeks.	Drug: Placebo; Three placebo tablets administered orally once daily for 12 weeks.
Experimental: Gemcabene 600 mg; Participants on stable statin therapy received 600 milligrams (mg) of Gemcabene orally, once daily for 12 weeks.	Drug: Gemcabene; Two 300 mg tablets and 1 placebo tablet administered orally, once daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in LDL-C at Week 12	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in LDL-C by Statin Intensity Stratum	The intensity of statin therapy was determined based on the statin dose.Participants were categorized as high intensity & moderate intensity based on their statin doses.	Baseline, Week 12
Change From Baseline in LDL-C		Baseline, Weeks 2, 4, 8, 12 and average of weeks 8 and 12
Percent Change From Baseline in LDL-C		Baseline, average of weeks 8 and 12
Percent Change From Baseline in Non-HDL-C		Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Non-HDL-C		Baseline, Weeks 2, 4, 8 and 12
Percent Change From Baseline in TC		Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in TC		Baseline, Weeks 2, 4, 8 and 12
Percent Change From Baseline in TG		Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in TG		Baseline, Weeks 2, 4, 8 and 12
Percent Change From Baseline in VLDL-C		Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in VLDL-C		Baseline, Weeks 2, 4, 8 and 12
Percent Change From Baseline in HDL-C		Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in HDL-C		Baseline, Weeks 2, 4, 8 and 12
Number of Participants Achieving LDL-C Reduction of ≥10%		Weeks 4, 8 and 12
Number of Participants Achieving LDL-C Reduction of ≥15%		Weeks 4, 8 and 12
Number of Participants Achieving LDL-C Reduction of ≥20%		Weeks 4, 8 and 12
Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L)		Weeks 4, 8 and 12
Percent Change From Baseline in Apolipoprotein B		Baseline, Weeks 4, 8 and 12
Change From Baseline in Apolipoprotein B		Baseline, Weeks 4, 8 and 12
Percent Change From Baseline in Apolipoprotein A-I		Baseline, Weeks 4, 8 and 12
Change From Baseline in Apolipoprotein A-I		Baseline, Weeks 4, 8 and 12
Percent Change From Baseline in Apolipoprotein A-II		Baseline, Weeks 4, 8 and 12
Change From Baseline in Apolipoprotein A-II		Baseline, Weeks 4, 8 and 12
Percent Change From Baseline in Apolipoprotein C-II		Baseline, Weeks 4, 8 and 12
Change From Baseline in Apolipoprotein C-II		Baseline, Weeks 4, 8 and 12
Percent Change From Baseline in Apolipoprotein C-III		Baseline, Weeks 4, 8 and 12
Change From Baseline in Apolipoprotein C-III		Baseline, Weeks 4, 8 and 12
Percent Change From Baseline in Apolipoprotein E		Baseline, Weeks 4, 8 and 12
Change From Baseline in Apolipoprotein E		Baseline, Weeks 4, 8 and 12
Percent Change From Baseline in Lipoprotein(a)		Baseline, Weeks 4, 8 and 12
Change From Baseline in Lipoprotein(a)		Baseline, Weeks 4, 8 and 12
Percent Change From Baseline in High-sensitivity C-reactive Protein		Baseline, Week 12
Change From Baseline in High-sensitivity C-reactive Protein		Baseline, Week 12
Percent Change From Baseline in Fibrinogen		Baseline, Week 12
Change From Baseline in Fibrinogen		Baseline, Week 12
Percent Change From Baseline in Serum Amyloid A		Baseline, Week 12
Change From Baseline in Serum Amyloid A		Baseline, Week 12
Percent Change From Baseline in Adiponectin		Baseline, Week 12
Change From Baseline in Adiponectin		Baseline, Week 12
Change From Baseline in Framingham Risk Score	Framingham Risk Score was an estimate of a participant's 10-year risk of developing cardiovascular disease which was computed using sex-specific algorithms based on total point score (range less than negative 3 [best] to greater than or equal to 14 [worst] for men; less than or equal to negative 2 [best] and greater than or equal to 17 [worst] for women) : which was derived of participant's age, systolic blood pressure , smoking status, TC, HDL-C, treatment for hypertension, and diabetes status. Reported score is a percentage. Change from baseline calculated as mean at week 12 minus mean at baseline. Negative scores indicate less risk of developing cardiovascular disease.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: NeuroBo Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimate): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): June 25, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: LDL-C; Lipid Regulator
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: GEM-301