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