Efficacy and Safety Study of HS-25 in Chinese Adults With Primary Hypercholesterolemia

Study Overview
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Brief Summary
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To determine the efficacy of HS-25 (20mg) in reducing low density lipoprotein-cholesterol (LDL-C) levels after a 12-week period of treatment in adults with primary hypercholesterolemia; To determine the safety of HS-25 (20mg) in subjects with LDL-C

Detailed Description
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This is a 12-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 3.36-4.88mmol/L(130-189 mg/dL)and fasting triglyceride levels < 350 mg/dL. Eligibility is restricted to 18-75 years 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.

Official Title
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Multi-center,Randomized,Double Blind,Placebo Controlled,Efficacy and Safety Study of HS-25 in Adults With Primary Hypercholesterolemia

Conditions
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Primary Hypercholesterolemia

Intervention / Treatment
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* Drug: HS-25
* Drug: Placebo of HS-25


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are 18 to 75 years of age, male or female using a highly effective birth control method or not of child-bearing potential, 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 12% 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 Signed written informed consent. Exclusion Criteria: Liver transaminases > 1.5 x upper limit of normal. Homozygous Familial Hypercholesterolemia. Subject who was diagnosed as diabetes with aged greater than 40 years old. Subject who was diagnosed as diabetes with one of the following of cardiovascular risk factorss: Hypertention Bp ≥ 140/90mmHg,or smoking, or low HDL-C (1.04mmol/L), or BMI≥28kg/m2. Women who are pregnant or breast feeding. Atherosclerotic cardiovascular disease including Arteriosclerotic heart disease, Acute coronary syndrome，Coronary artery bypass graft,Coronary angioplastyPeripheral arteriosclerosis,Cerebrovascular accident history of Severe Endiocrine disease (for example Thyroid function abnormal) History of a positive test for human immunodeficiency virus, hepatitis B or hepatitis C. History of advanced cancer Arrhythmias need to be treated by medications Had severe injured or surgery in 6 months before study start. Hypersensitive to HS-25 or place. History of intolerance to ezetimibe. Participation other studies in three months. Treatment with a fibric acid derivative (eg, fenofibrate, gemfibrozil), probucol, warfarin, systemic corticosteroid, cyclosporine or other immunosuppressant agent within the prior 12 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HS-25<br>20mg, QD, 12 weeks | Drug: HS-25<br>* HS-25 10mg/tablet, 20mg,once daily,for 12 weeks, and then HS-25 20mg once daily for 40 weeks.<br>|
| Placebo Comparator: Placebo of HS-25<br>20mg, QD, 12 weeks | Drug: HS-25<br>* HS-25 10mg/tablet, 20mg,once daily,for 12 weeks, and then HS-25 20mg once daily for 40 weeks.<br>Drug: Placebo of HS-25<br>* Placebo HS-25 10mg/tablet, 20mg,once daily,for 12 weeks,and then HS-25 20mg once daily for 40 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C | Percent change from baseline in LDL-C after 2,4,8,12,18,24,38,52 weeks of double-blind treatment | 2,4,8,12,18,24,38,52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-HDL-C | Percent change from baseline in LDL-C after 2,4,8,12,18,24,38,52 weeks of double-blind treatment | 2,4,8,12,18,24,38,52 weeks | 
| HDL-C | Percent change from baseline in LDL-C after 2,4,8,12,18,24,38,52 weeks of double-blind treatment | 2,4,8,12,18,24,38,52 weeks | 
| TC | Percent change from baseline in LDL-C after 2,4,8,12,18,24,38,52 weeks of double-blind treatment | 2,4,8,12,18,24,38,52 weeks | 
| TG | Percent change from baseline in LDL-C after 2,4,8,12,18,24,38,52 weeks of double-blind treatment | 2,4,8,12,18,24,38,52 weeks |