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

Hypercholesteremia Clinical Trial

— ROYAL-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02634151
• Other study ID #: GEM-301
• Status: Completed
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: August 2017

Study information

• Verified date: June 2020
• Source: NeuroBo Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: August 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hypercholesteremia
• Hypercholesterolemia

Intervention

Drug:
• Gemcabene
Two 300 mg tablets and 1 placebo tablet administered orally, once daily for 12 weeks.
• Placebo
Three placebo tablets administered orally once daily for 12 weeks.

Locations

Country	Name	City	State
United States	Atlantic Clinical Research Collaborative- Cardiology	Atlantis	Florida
United States	Westside Medical Associates of Los Angeles	Beverly Hills	California
United States	Central Research Associates, Inc.	Birmingham	Alabama
United States	Excel Medical Clinical Trials	Boca Raton	Florida
United States	Sentral Clinical Research Services	Cincinnati	Ohio
United States	Sterling Research Group, Ltd.	Cincinnati	Ohio
United States	Sterling Research Group, Ltd.	Cincinnati	Ohio
United States	Evanston Premier Healthcare Research, LLC	Evanston	Illinois
United States	Associates in Medicine	Houston	Texas
United States	National Research Institute	Huntington Park	California
United States	Midwest Institute for Clinical Research	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Health Awareness, Inc.	Jupiter	Florida
United States	Green and Seidner Family Practice Associates	Lansdale	Pennsylvania
United States	National Research Institute	Los Angeles	California
United States	L-MARC	Louisville	Kentucky
United States	Meridien Research, Inc.	Maitland	Florida
United States	Mid-Hudson Medical Research	New Windsor	New York
United States	Progressive Medical Research	Port Orange	Florida
United States	National Research Institute	Richmond	Virginia
United States	Rochester Clinical Research, Inc.	Rochester	New York
United States	Diagnostics Research Grup	San Antonio	Texas
United States	Sugar Lakes Family Practice	Sugar Land	Texas
United States	Varkey Medical	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
NeuroBo Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in LDL-C at Week 12		Baseline, Week 12
Secondary	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
Secondary	Change From Baseline in LDL-C		Baseline, Weeks 2, 4, 8, 12 and average of weeks 8 and 12
Secondary	Percent Change From Baseline in LDL-C		Baseline, average of weeks 8 and 12
Secondary	Percent Change From Baseline in Non-HDL-C		Baseline, Weeks 2, 4, 8 and 12
Secondary	Change From Baseline in Non-HDL-C		Baseline, Weeks 2, 4, 8 and 12
Secondary	Percent Change From Baseline in TC		Baseline, Weeks 2, 4, 8 and 12
Secondary	Change From Baseline in TC		Baseline, Weeks 2, 4, 8 and 12
Secondary	Percent Change From Baseline in TG		Baseline, Weeks 2, 4, 8 and 12
Secondary	Change From Baseline in TG		Baseline, Weeks 2, 4, 8 and 12
Secondary	Percent Change From Baseline in VLDL-C		Baseline, Weeks 2, 4, 8 and 12
Secondary	Change From Baseline in VLDL-C		Baseline, Weeks 2, 4, 8 and 12
Secondary	Percent Change From Baseline in HDL-C		Baseline, Weeks 2, 4, 8 and 12
Secondary	Change From Baseline in HDL-C		Baseline, Weeks 2, 4, 8 and 12
Secondary	Number of Participants Achieving LDL-C Reduction of =10%		Weeks 4, 8 and 12
Secondary	Number of Participants Achieving LDL-C Reduction of =15%		Weeks 4, 8 and 12
Secondary	Number of Participants Achieving LDL-C Reduction of =20%		Weeks 4, 8 and 12
Secondary	Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L)		Weeks 4, 8 and 12
Secondary	Percent Change From Baseline in Apolipoprotein B		Baseline, Weeks 4, 8 and 12
Secondary	Change From Baseline in Apolipoprotein B		Baseline, Weeks 4, 8 and 12
Secondary	Percent Change From Baseline in Apolipoprotein A-I		Baseline, Weeks 4, 8 and 12
Secondary	Change From Baseline in Apolipoprotein A-I		Baseline, Weeks 4, 8 and 12
Secondary	Percent Change From Baseline in Apolipoprotein A-II		Baseline, Weeks 4, 8 and 12
Secondary	Change From Baseline in Apolipoprotein A-II		Baseline, Weeks 4, 8 and 12
Secondary	Percent Change From Baseline in Apolipoprotein C-II		Baseline, Weeks 4, 8 and 12
Secondary	Change From Baseline in Apolipoprotein C-II		Baseline, Weeks 4, 8 and 12
Secondary	Percent Change From Baseline in Apolipoprotein C-III		Baseline, Weeks 4, 8 and 12
Secondary	Change From Baseline in Apolipoprotein C-III		Baseline, Weeks 4, 8 and 12
Secondary	Percent Change From Baseline in Apolipoprotein E		Baseline, Weeks 4, 8 and 12
Secondary	Change From Baseline in Apolipoprotein E		Baseline, Weeks 4, 8 and 12
Secondary	Percent Change From Baseline in Lipoprotein(a)		Baseline, Weeks 4, 8 and 12
Secondary	Change From Baseline in Lipoprotein(a)		Baseline, Weeks 4, 8 and 12
Secondary	Percent Change From Baseline in High-sensitivity C-reactive Protein		Baseline, Week 12
Secondary	Change From Baseline in High-sensitivity C-reactive Protein		Baseline, Week 12
Secondary	Percent Change From Baseline in Fibrinogen		Baseline, Week 12
Secondary	Change From Baseline in Fibrinogen		Baseline, Week 12
Secondary	Percent Change From Baseline in Serum Amyloid A		Baseline, Week 12
Secondary	Change From Baseline in Serum Amyloid A		Baseline, Week 12
Secondary	Percent Change From Baseline in Adiponectin		Baseline, Week 12
Secondary	Change From Baseline in Adiponectin		Baseline, Week 12
Secondary	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