Clinical trial NCT02634151: A 12-Week, Phase 2 Study of Gemcabene in Hypercholesterolemia Patients on Stable Moderate and High-Intensity Statins
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesteremia
Keywords: LDL-C
Lipid Regulator
Lead sponsor: NeuroBo Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-17
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percent Change From Baseline in LDL-C at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percent Change From Baseline in LDL-C by Statin Intensity Stratum
timeFrame: Baseline, Week 12
measure: Change From Baseline in LDL-C
timeFrame: Baseline, Weeks 2, 4, 8, 12 and average of weeks 8 and 12
measure: Percent Change From Baseline in LDL-C
timeFrame: Baseline, average of weeks 8 and 12
measure: Percent Change From Baseline in Non-HDL-C
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in Non-HDL-C
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Percent Change From Baseline in TC
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in TC
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Percent Change From Baseline in TG
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in TG
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Percent Change From Baseline in VLDL-C
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in VLDL-C
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Percent Change From Baseline in HDL-C
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in HDL-C
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Number of Participants Achieving LDL-C Reduction of ≥10%
timeFrame: Weeks 4, 8 and 12
measure: Number of Participants Achieving LDL-C Reduction of ≥15%
timeFrame: Weeks 4, 8 and 12
measure: Number of Participants Achieving LDL-C Reduction of ≥20%
timeFrame: Weeks 4, 8 and 12
measure: Number of Participants Achieving an LDL-C Value <100 mg/dL (2.59 mmol/L)
timeFrame: Weeks 4, 8 and 12
measure: Percent Change From Baseline in Apolipoprotein B
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Apolipoprotein B
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Percent Change From Baseline in Apolipoprotein A-I
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Apolipoprotein A-I
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Percent Change From Baseline in Apolipoprotein A-II
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Apolipoprotein A-II
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Percent Change From Baseline in Apolipoprotein C-II
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Apolipoprotein C-II
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Percent Change From Baseline in Apolipoprotein C-III
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Apolipoprotein C-III
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Percent Change From Baseline in Apolipoprotein E
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Apolipoprotein E
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Percent Change From Baseline in Lipoprotein(a)
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Lipoprotein(a)
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Percent Change From Baseline in High-sensitivity C-reactive Protein
timeFrame: Baseline, Week 12
measure: Change From Baseline in High-sensitivity C-reactive Protein
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Fibrinogen
timeFrame: Baseline, Week 12
measure: Change From Baseline in Fibrinogen
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Serum Amyloid A
timeFrame: Baseline, Week 12
measure: Change From Baseline in Serum Amyloid A
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Adiponectin
timeFrame: Baseline, Week 12
measure: Change From Baseline in Adiponectin
timeFrame: Baseline, Week 12
measure: Change From Baseline in Framingham Risk Score
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates, Inc.
state: Alabama
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Atlantis
country: United States
facility: Atlantic Clinical Research Collaborative- Cardiology
state: Florida
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Maitland
country: United States
facility: Meridien Research, Inc.
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Tampa
country: United States
facility: Varkey Medical
state: Florida
city: Evanston
country: United States
facility: Evanston Premier Healthcare Research, LLC
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Louisville
country: United States
facility: L-MARC
state: Kentucky
city: New Windsor
country: United States
facility: Mid-Hudson Medical Research
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd.
state: Ohio
city: Cincinnati
country: United States
facility: Sentral Clinical Research Services
state: Ohio
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd.
state: Ohio
city: Lansdale
country: United States
facility: Green and Seidner Family Practice Associates
state: Pennsylvania
city: Houston
country: United States
facility: Associates in Medicine
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Grup
state: Texas
city: Sugar Land
country: United States
facility: Sugar Lakes Family Practice
state: Texas
city: Richmond
country: United States
facility: National Research Institute
state: Virginia
Study officials:
References: