A 4-week, Randomized, Placebo-Controlled, Double-Blind, Efficacy and Safety Study of HS-25 in Adults With Primary Hypercholesterolemia
- Registration Number
- NCT02087917
- Lead Sponsor
- Zhejiang Hisun Pharmaceutical Co. Ltd.
- Brief Summary
To determine the efficacy of HS-25 (5, 10, 20 or 30 mg) in reducing low density lipoprotein-cholesterol (LDL-C) levels after a 4-week period of treatment in adults with primary hypercholesterolemia.
- Detailed Description
This is a 4-week, randomized, double-blind, placebo-controlled study designed to assess the effects of the cholesterol absorption inhibitor HS-25 on LDL-C levels in adults who have untreated LDL-C levels ranging from 130-189 mg/dL and fasting triglyceride levels \< 350 mg/dL. Eligibility is restricted to 18-65 year old men or women who are using a highly effective birth control method or are not of childbearing potential. Patients with diabetes, a history of myocardial infarction or other clinical evidence of atherosclerotic vascular disease are not eligible for participation in the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 376
Inclusion Criteria
- Men, or women using a highly effective birth control method or not of child-bearing potential, who are 18 to 65 years of age at Visit 1 (screening visit).
- LDL-C 130 to 189 mg/dL (inclusive) on a cholesterol lowering diet but no lipid modifying drug treatment for at least 6 weeks. A qualifying LDL-C value must be obtained at the beginning and end of the placebo run-in (Visit 2 and Visit 3) and the Visit 3 value must be within 15% of the value at Visit 2, higher or lower; the average of both qualifying values must be in the range of 130 to 189 mg/dL (inclusive) for inclusion in the study.
- TG ≤ 350 mg/dL on a cholesterol lowering diet but no lipid modifying drug treatment for at least 6 weeks and TG levels must be ≤ 350 mg/dL at both Visit 2 and Visit 3
- Compliance of 80% to 120% with assigned study drug regimen during a 2 week placebo run-in phase.
Exclusion Criteria
- Women who are pregnant or breast feeding.
- History of stroke, myocardial infarction, unstable angina, heart failure or any arterial revascularization procedure (eg, carotid, coronary, aorta, peripheral arterial).
- History of diabetes or glycosylated hemoglobin (HbA1c) > 6.5.
- History of moderate to severe lactose intolerance (eg, unable to drink a glass of milk).
- History of hospitalization for treatment of a major psychiatric disorder.
- History of drug or alcohol abuse as defined by the Diagnostic and Statistical Manual (DSM-5) within the prior 12 months.
- History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months prior to screening.
- Hospitalization for a duration > 24 hours for any reason within the prior 3 months that, in the opinion of the investigator, may affect adherence to study procedures.
- History of a positive test for human immunodeficiency virus, hepatitis B or hepatitis C.
- History of cancer with the exception of well-treated basal cell or squamous cell carcinoma of skin, or in-situ cervical carcinoma.
- Presence of any condition which, in the opinion of the investigator, is likely to compromise completion of this trial or not be in the best interest of the subject.
- History of intolerance to ezetimibe.
- Participation in a prior study of HS 25.
- Participation in a study of an investigational drug or device within the prior 3 months unless subject has documentation of placebo administration in a placebo-controlled drug treatment trial only.
- Treatment with a fibric acid derivative (eg, fenofibrate, gemfibrozil), probucol, warfarin, systemic corticosteroid, cyclosporine or other immunosuppressant agent within the prior 12 weeks.
- Anticipated need or frequent use of acetaminophen (> 2 gm/day, that is required > 4x/week).
- Vitamins, herbal and dietary supplements must be discontinued at screening unless subject has been on a long-term daily regimen and agrees to continue this regimen during the study.
- Alanine aminotransferase (ALT) > 1.0 × upper limit of normal (ULN) at Visit 1, Visit 2 or Visit 3.
- Aspartate aminotransferase (AST) > 1.0 × ULN at Visit 1, Visit 2 or Visit 3.
- Unexplained (not due to exercise or strenuous activity) creatinine kinase increase > 2 × ULN at Visit 1, Visit 2 or Visit 3.
- Estimated glomerular filtration rate (Modification of Diet in Renal Disease) < 60 mL/min/1.73m2 at Visit 1, Visit 2 or Visit 3.
- Thyroid stimulating hormone outside of the normal range.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical disease (eg, infectious disease) must not be enrolled.
- Any other laboratory abnormality considered by the investigator to be clinically significant.
- Any subject with an electrocardiogram (ECG) having a QTc interval ≥ 450 msec, or any other abnormality considered by the investigator to be clinically significant at the end of placebo run-in (Visit 3) should not be enrolled.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - HS-25 20 MG HS-25 - HS-25 5 MG HS-25 - HS-25 10 MG HS-25 - HS-25 30 MG HS-25 -
- Primary Outcome Measures
Name Time Method Percent change from baseline in LDL-C after 4 weeks of double-blind treatment 4 weeks
- Secondary Outcome Measures
Name Time Method Percent change from baseline in LDL-C after a 1 and 2-week period of double-blind treatment 1- and 2-weeks Percentage of participants with reported adverse events during a 4-week period of treatment as a measure of safety and tolerability of HS-25 4 weeks Mean concentration of HS-25 dose and its major metabolite (HS-25-M1) during treatment with HS-25 5, 10, 20 or 30 mg. 1-, 2- and 4-week Percent change from baseline in apoprotein B, non-high density lipoprotein-cholesterol, total cholesterol, triglycerides, high density lipoprotein-cholesterol and apoprotein A1 levels after a 1, 2 and 4-week period of treatment 1-, 2- and 4-week periods Correlation between trough HS-25 and HS-25-M1 levels and percent change in LDL-C, apoA1, apoB, non-HDL-C, TC, TG, and HDL-C during a 4-week period of HS-25 treatment. 1-, 2- and 4-week