A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia

This is a randomized, double-blind, placebo-controlled, multi-center, cross-over study of
the efficacy, safety and tolerability rosuvastatin in children and adolescents (aged 6 to
<18 years) with homozygous familial hypercholesterolemia (HoFH). The study is designed to
assess the efficacy of rosuvastatin 20 mg compared to placebo on lipids, lipoproteins and
apolipoproteins in pediatric patients with HoFH. The outcome measures to be assessed
include low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol
(HDL-C), total cholesterol (TC), triglycerides, non-HDL-C, LDL-C/HDL-C, TC/HDL-C,
non-HDL-C/HDL-C, apolipoprotein B (ApoB), apolipoprotein A 1 (ApoA-1) and ApoB/ApoA-1
following 6 weeks of treatment with rosuvastatin 20 mg or placebo. Pharmacokinetic data of
the trough plasma exposure of rosuvastatin will also be assessed in these pediatric patients
with HoFH.

Inclusion Criteria:

1. Prior to any study related procedures being performed, provision of written informed
consent from a parent/both parents or guardian and statement of assent from the child
or adolescent (if required by Institutional Review Board [IRB] or Independent Ethics
Committee [EC] according to local regulations and guidelines). Communication between
the Investigator, patient/guardian and child/adolescent to confirm understanding and
required compliance with the requirements of the study.

2. Male and female children and adolescents (aged 6 to <18 years) with at least 1 of the
following criteria:

Documentation of genetic testing confirming 2 mutated alleles of the LDL receptor
gene locus; and/or

Documented untreated LDL C >500 mg/dL (12.9 mmol/L) and triglyceride (TG) <300 mg/dL
(3.4 mmol/L) and at least 1 of the following criteria:

1. Tendinous and/or cutaneous xanthoma prior to 10 years of age; or

2. Documentation of HoFH in both parents by:

- genetic and/or

- clinical criteria

3. Negative pregnancy test (b human chorionic gonadotropin analysis) prior to baseline
in females of child bearing potential:

- Female patients of child bearing potential must adhere to a pregnancy prevention
method (abstinence, chemical, or mechanical) during the study and 3 months
following the last dose.

- Male patients should refrain from fathering a child (including sperm donation)
during the study and up to 3 months following the last dose; and

4. Willing to follow all study procedures including adherence to dietary guidelines,
study visits, fasting blood draws, and compliance with study treatment regimens.

Exclusion Criteria

1. History of statin inducted myopathy or serious hypersensitivity reaction to other HMG
CoA reductase inhibitors (statins), including rosuvastatin, at Visit 1.

2. Fasting serum glucose of >9.99 mmol/L (180 mg/dL) or glycosylated hemoglobin >9% at
Visit 1 or patients with a history of diabetic ketoacidosis within the past year.

3. Uncontrolled hypothyroidism defined as thyroid stimulating hormone (TSH) >1.5 times
the upper limit of normal (ULN) at Visit 1 or patients whose thyroid replacement
therapy was initiated or modified within the last 3 months prior to Visit 2.

4. Current active liver disease or hepatic dysfunction (except a confirmed diagnosis of
Gilbert's disease) as defined as elevations of 1.5 times the upper limit of normal
(ULN) for any age in any of the following liver function tests at Visit 1: Alanine
Aminotransferase (ALT), Aspartate Aminotransferase (AST), or bilirubin.

5. Definite or suspected personal history or family history of clinically significant
adverse drug reactions (ADRs), or hypersensitivity to drugs with a similar chemical
structure to rosuvastatin as well as other statins.