A Randomized, Double-blind, Placebo-controlled, Multi-center, Cross-over Study of Rosuvastatin in Children and Adolescents (aged 6 to <18 years) with Homozygous Familial Hypercholesterolemia (HoFH)
- Conditions
- hypercholesterolemiaMetabolism10013317
- Registration Number
- NL-OMON41938
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
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 either the
LDL receptor gene locus, ApoB, or PCSK9; and/or
* Documented untreated LDL-C >500 mg/dL (12.9 mmol/L) and triglyceride
(TG) <400 mg/dL (4.5 mmol/L) and at least 1 of the following criteria:
o Tendinous and/or cutaneous xanthoma prior to 10 years of age; or
o Documentation of HeFH 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.
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 ALT or AST elevations of 2 times the ULN for any
age, or bilirubin elevation of 1.5 times the ULN for any age at Visit 1;
5. Serum CK *3 times ULN (unless explained by exercise) at Visit 1. If CK *3 times
ULN is assessed to be explained by exercise, retesting may be performed at Visit 2;
6. Estimated glomerular filtration rate by Schwartz formula <50 mL/min at Visit 1;
7. A *2+ proteinuria on urine dipstick at Visit 1;
8. Stage 2 hypertension (systolic and/or diastolic blood pressure greater than 5 mmHg
above the 99th percentile for age, gender, and height) at Visit 1;
9. History of solid organ transplantation at Visit 1;
10. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and representatives and/or staff at the study site);
11. Previous randomization in the present study;
12. Participation in a clinical study where an investigational product was ingested
during the last 30 days before Visit 2 of the current study;
13. Any clinically significant acute illness within 2 weeks before the start of the study
(Visit 1);
14. Any clinically significant abnormalities in clinical chemistry, hematology, or
urinalysis results at the discretion of the Investigator;
15. Any contraindication from the following: a detailed medical and drug history, a
complete physical examination including vital signs, blood chemistry, hematology,
coagulation factors, and urinalysis;
16. 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;
17. History or presence of gastrointestinal, hepatic, or renal disease or other condition
known to interfere with absorption, distribution, metabolism, or excretion of drugs;
18. Treatment in the previous 3 months with any drug known to have a well-defined
potential for hepatotoxicity (eg, halothane);
19. Clinical judgement by the Investigator that the patient should not participate in the
study;
20. Patients weighing <20 kg (44 lbs);
21. Pregnancy or currently lactating; or
22. Patients planning to start apheresis during the study period.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>LDL-C following 6 weeks of treatment with rosuvastatin 20 mg or placebo</p><br>
- Secondary Outcome Measures
Name Time Method <p>- LDL-C following 6 weeks of treatment with rosuvastatin 20 mg or placebo in<br /><br>patients not treated with apheresis<br /><br>- High-density lipoprotein cholesterol (HDL-C), total cholesterol (TC),<br /><br>triglyceride (TG), non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C,<br /><br>apolipoprotein B (ApoB), ApoB/apolipoprotein A-1 (ApoA-1) and ApoA-1 following<br /><br>6 weeks of treatment with rosuvastatin 20 mg or placebo<br /><br>- Change in LDL-C from end of placebo period to 6, 12, and 18 weeks of therapy<br /><br>with rosuvastatin 20 mg<br /><br>- Rosuvastatin trough concentrations</p><br>