Higher-Dose Ezetimibe to Treat Homozygous Sitosterolemia

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00099996
• Date of registration: 21/12/2004
• Prospective Registration: No
• Primary sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Public title: Higher-Dose Ezetimibe to Treat Homozygous Sitosterolemia
• Scientific title: A Study to Assess Adding Ezetimibe 30 mg to Ongoing Treatment With Ezetimibe 10 mg in Patients With Homozygous Sitosterolemia
• Date of first enrolment: December 2004
• Target sample size: 3
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00099996
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

United States

Key inclusion & exclusion criteria

INCLUSION CRITERIA:

To be enrolled into this study, patients must meet all of the following criteria:

1. Patient is at least 18 years of age and no greater than 85 years of age as of Visit
1.

2. Patient has a diagnosis of homozygous sitosterolemia, with a history of a plasma
sitosterol concentration greater than 5 mg/dL (0.13 mmol/L).

3. Patient has been on an ongoing stable regimen of ezetimibe 10 mg daily for at least 6
months prior to Visit 1.

4. If patient is currently on a treatment for sitosterolemia (in addition to ezetimibe
10 mg), treatment regimen must be stable for at least 4 weeks prior to visit 1.

Note: Treatments may include bile salt binding resins, statins, and/or apheresis.

5. Patient must be willing to maintain their current treatment regimen for the duration
of the study.

6. Patient must be on a stable diet for at least 4 weeks prior to visit 1.

7. Patient must be willing to maintain this diet for the duration of the study.

8. Patient is a man or postmenopausal woman. Patient is a premenopausal woman who is
either surgically sterilized or highly unlikely to conceive, and has a negative urine
beta-hCG pregnancy test within 72 hours prior to the start of study treatment.

Note: Highly unlikely to conceive is defined as a woman who: (1) has vasectomized
partners, or (2) has a copper intrauterine device (IUD) in place for greater than 3 months
without complaint, or (3) abstains from heterosexual intercourse, or (4) agrees to use a
double-barrier method of contraception, or (5) is using noncyclical oral contraceptive.

EXCLUSION CRITERIA:

1. Patient has a condition which, in the opinion of the investigator, might pose a risk
to the patient, interfere with participation in the study, or does not meet criteria
for this protocol.

MEDICAL HISTORY AND LABORATORY ABNORMALITIES PRIOR TO RANDOMIZATION:

2. Patient has clinically significant laboratory abnormalities at visit 1 and/or last
available laboratory results prior to visit 2:

i. ALT (SGPT) greater than or equal to 3 x ULN (75 mU/mL or 75 IU/L).

ii. AST (SGOT) greater than or equal to 3 x ULN (66 mU/mL or 66 IU/L).

iii. TSH greater than 6 microIU/mL or 6mIU/L - or change in medication for hypothyroidism
within 6 weeks prior to visit 1.

iv. CPK greater than or equal to 3 x ULN (360 mg/dL or 360 IU/L) and persistent elevation
at redraw with muscle symptoms consistent with myopathy.

c. Patient has known hypersensitivity of contraindication to ezetimibe.

d. Patient is breast feeding.

e. Patient's weight is less than 40 kg.

f. Patient has been treated with any other investigational drug within 30 days prior to
visit 1.

PROHIBITED MEDICAL CONDITIONS:

g. Patient has uncontrolled cardiac arrhythmias.

h. Patient has had unstable angina pectoris within 1 month of visit 1.

i. Patient has severe/unstable peripheral vascular disease.

j. Patient has had symptomatic carotid disease (transient ischemic attack, stroke) within
1 month of visit 1.

k. Patient had a myocardial infarction within 1 month of visit 1.

l. Patient had a coronary artery bypass surgery, or other invasive coronary procedure
within 1 month of visit 1.

m. Patient has a very poorly controlled Type 1 or Type 2 diabetes mellitus (HbA1c at
visit 1 greater than 10%), or has had antidiabetic regimen changed within the 8 weeks
prior to visit 1.

n. Patient has uncontrolled hypertension (systolic BP greater than 180 mm Hg and/or
diastolic BP greater than 110 mm Hg).

o. Patient has impaired renal function (creatinine greater than 2.0 mg/dL or 176.80
micromol/L), or nephritic syndrome at Visit 1.

p. Patient has active or chronic hepatobiliary disease or hepatic disease.

q. Patient is known to be positive for human immunodeficiency (HIV).

r. Patient has a history of severe psychiatric illness, drug/alcohol abuse within the
past 5 years, or major psychiatric illness not adequately controlled and stable on
pharmacotherapy.

s. Patient had cancer within the past 5 years (except for successfully treated basal and
squamous cell carcinomas of the skin).

CONCOMITANT MEDICATIONS/TREATMENTS:

t. Patient is on a statin and is treated with, or likely to require treatment with, an
agent that has precautions or contraindications to concomitant use with the statin.

Note: These agents include those with known interactions with statins: antifungal azoles
(itraconazole and ketoconazole), macrolide antibiotics (erythromycin and clarithromycin),
nefazodone, verapamil, amiodarone, and protease inhibitors.

u. Patient is taking oral corticosteroids UNLESS patient uses as stable replacement
therapy for pituitary/adrenal disease. For these indications, patients must be on a
stable regimen for at least 3 months prior to visit 1.

v. Patient is on a thiazide diuretic UNLESS treated with a stable regimen for at least 6
weeks prior to visit 1, and expected to remain stable for the duration of the study.

w. Patient had ileal bypass surgery within 3 months prior to visit 1.

x. Patient is currently taking margarines containing phytosterols/phytostanols or other
supplements/medications known to increase sitosterol and campesterol concentrations.



Age minimum: N/A
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Heart Diseases

Metabolism, Inborn Errors

Intervention(s)

Drug: Ezetimibe

Drug: SCH-58235

Secondary ID(s)

050060

05-H-0060

Source(s) of Monetary Support

Please refer to primary and secondary sponsors