Efficacy and Safety Study of HS-25 in Chinese Adults With Primary Hypercholesterolemia (HS-25-III-01)

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

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

Study Overview

• Status: Completed
• Conditions: Primary Hypercholesterolemia
• Intervention / Treatment: Drug: HS-25; Drug: Placebo of HS-25

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 374
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: HS-25; 20mg, QD, 12 weeks	Drug: HS-25; HS-25 10mg/tablet, 20mg,once daily,for 12 weeks, and then HS-25 20mg once daily for 40 weeks.
PLACEBO_COMPARATOR: Placebo of HS-25; 20mg, QD, 12 weeks	Drug: HS-25; HS-25 10mg/tablet, 20mg,once daily,for 12 weeks, and then HS-25 20mg once daily for 40 weeks.; Drug: Placebo of HS-25; Placebo HS-25 10mg/tablet, 20mg,once daily,for 12 weeks,and then HS-25 20mg once daily for 40 weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhejiang Hisun Pharmaceutical Co. Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 12, 2016
• Primary Completion (ACTUAL): April 20, 2018
• Study Completion (ACTUAL): September 20, 2018

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (ACTUAL): January 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: HS-25-III-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No