A 4-week, Randomized, Placebo-Controlled, Double-Blind, Efficacy and Safety Study of HS-25 in Adults With Primary Hypercholesterolemia

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Phoenix, Arizona, United States
  • California
    • West Hills, California, United States
  • Florida
    • Doral, Florida, United States
    • Jacksonville, Florida, United States
    • Miami, Florida, United States
    • South Miami, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
  • Indiana
    • Evansville, Indiana, United States
    • Indianapolis, Indiana, United States
  • Kansas
    • Overland Park, Kansas, United States
  • Kentucky
    • Louisville, Kentucky, United States
  • Maine
    • Auburn, Maine, United States
  • Maryland
    • Bethesda, Maryland, United States
  • Massachusetts
    • Methuen, Massachusetts, United States
  • New Jersey
    • Trenton, New Jersey, United States
  • New York
    • Rochester, New York, United States
  • North Carolina
    • Raleigh, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Oklahoma
    • Tulsa, Oklahoma, United States
  • Pennsylvania
    • Penndel, Pennsylvania, United States
  • South Carolina
    • Greensboro, South Carolina, United States
  • Texas
    • Dallas, Texas, United States
    • Houston, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States
  • Virginia
    • Norfolk, Virginia, United States
    • Richmond, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Assigned study drug (HS-25 or placebo) is to be administered orally once daily in the morning with or without food. Treatment duration 4 weeks.
Active Comparator: HS-25 5 MG	Drug: HS-25; Assigned study drug (HS-25 or placebo) is to be administered orally once daily in the morning with or without food. Treatment duration 4 weeks.
Active Comparator: HS-25 10 MG	Drug: HS-25; Assigned study drug (HS-25 or placebo) is to be administered orally once daily in the morning with or without food. Treatment duration 4 weeks.
Active Comparator: HS-25 20 MG	Drug: HS-25; Assigned study drug (HS-25 or placebo) is to be administered orally once daily in the morning with or without food. Treatment duration 4 weeks.
Active Comparator: HS-25 30 MG	Drug: HS-25; Assigned study drug (HS-25 or placebo) is to be administered orally once daily in the morning with or without food. Treatment duration 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in LDL-C after 4 weeks of double-blind treatment	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Percent change from baseline in LDL-C after a 1 and 2-week period of double-blind treatment	1- and 2-weeks
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
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
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

Collaborators and Investigators

• Sponsor: Zhejiang Hisun Pharmaceutical Co. Ltd.
• Collaborators: Covance
• Investigators: Study Director: Kevin Liao, PhD, Zhejiang Hisun Pharmaceuticals Co., Ltd

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: March 5, 2014
• First Submitted That Met QC Criteria: March 12, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Estimate): January 6, 2015
• Last Update Submitted That Met QC Criteria: January 5, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: hypercholesterolemia; cholesterol absorption inhibitor; placebo-controlled trial
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: HS-25-III