A randomized phase 2 study to determine the dose, and assessthe efficacy, safety, and tolerability of Gemcabene in Patients withHypercholesterolemia.
- Conditions
- HypercholesterolaemiaMedDRA version: 19.0Level: PTClassification code 10020603Term: HypercholesterolaemiaSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2015-005756-10-DK
- Lead Sponsor
- Gemphire Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 212
1. Provision of written and signed informed consent (by patient or legal guardian) prior to any study-specific procedure;
2. Male or female great than or equal to 18 years of age at time of consent;
3. Currently on a stable, low-fat, low-cholesterol diet in combination with atorvastatin (40 mg or 80 mg QD) or rosuvastatin (20 mg or 40 mg QD) with or without ezetimibe (10 mg QD) for at least 4 weeks prior to the Screening Visit;
4. Fasting LDL-C value great than 100 mg/dL at the Screening Visit;
5. Physical examination, including vital signs, that is within normal limits or clinically acceptable to the Investigator;
6. Weight great than or equal to 50 kg;
7. Female patients must not be pregnant or lactating. Women of child-bearing potential must have
a negative serum pregnancy test at the Screening Visit and negative urine dipstick on Day 1 prior to dosing in order to qualify for the study. Women who are surgically sterile or are clinically confirmed to be post-menopausal (i.e., documented amenorrhea for greater than or equal to 1 year in the absence of other biological or physiological causes) are not considered to be of child-bearing potential; and
8. Women of child-bearing potential must agree to use acceptable methods of contraception
throughout the duration of the study and for 30 days after the last dose of study drug. For this
study, double-barrier contraception is required.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32
1. Abnormal liver function test at the Pre-Screening Visit or the Screening Visit (aspartate aminotransferase or alanine aminotransferase greater than 2 × the upper limit of normal [ULN], total bilirubin greater than 1.5 × ULN, or alkaline phosphatase greater than 2 × ULN based on appropriate age and gender normal values). Patients with bilirubin greater than 1.5 × ULN and 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 [HBV], hepatitis C [HCV], autoimmune hepatitis, liver failure, liver cancer), history of liver transplant, known diagnosis of human immunodeficiency virus (HIV), or acquired immune deficiency virus;
4. Triglyceride value greater than 400 mg/dL at the Pre-Screening Visit or the Screening Visit;
5. Moderate to severe renal insufficiency defined as an estimated GFR less than 30 mL/min/1.73m2 (calculated using The Chronic Kidney Disease Epidemiology Collaboration equation) at the Pre-Screening Visit or the 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 ratio testing;
7. Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism as defined by thyroid-stimulating hormone (TSH) below the lower limit of normal or greater than 1.5 × 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 the Screening Visit;
8. Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (hemoglobin A1c [HbA1c] value greater than 8% based on results from the Pre-Screening Visit or the Screening Visit), or any diabetic patient taking insulin and/or thiazolidinediones;
9. New York Heart Association Class III or IV heart failure (see Appendix C);
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. Patients 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 greater than 180 mmHg or diastolic blood pressure greater than 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. Use 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;
17. History of drug or alcohol abu
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to assess the efficacy, safety, and tolerability of multiple doses of gemcabene compared to placebo in patients with hypercholesterolemia on a high-intensity stable statin therapy with or without ezetimibe.;Secondary Objective: To confirm the appropriate dose for use in Phase 3 registration studies as assessed by efficacy and safety data. <br>To further evaluate the efficacy of gemcabene as assessed by measurements of lipid and apolipoprotein parameters, hsCRP, and fibrinogen.<br>The exploratory objective of this study is to evaluate the effects of gemcabene on serum PCSK9 levels.;Primary end point(s): The primary efficacy analysis is the percent change in LDL-C from baseline to Day 28, Day 56,<br>and Day 84.;Timepoint(s) of evaluation of this end point: Day 28, Day 56, and Day 84
- Secondary Outcome Measures
Name Time Method