Heterozygous familial hypercholesterolemia (HeFH) is a frequent, inherited disorder of lipoprotein metabolism caused by mutations in the LDL receptor gene. The risk of CHD is approximately 50% by 50 years of age in untreated HeFH. Morphological and functional changes of the arteries are present in hypercholesterolemic children and can predict future CHD, underscoring the importance of aggressive and early treatment of dyslipidemia to prevent premature events in HeFH.
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study dietary lead in and double-blind period, patients must fulfill all of the following criteria: 1. Provision of written informed consent from a parent or guardian. Communication with the investigator and understanding and compliance with the requirements of the study by the patient and parent or guardian. Statement of assent from the child or adolescent as required by the IRB or IEC according to local regulations and guidelines 2. Male or female (Tanner stage II-V, at least 1 year post-menarche) children and adolescents (aged 10 –17 years) with heterozygous familial hypercholesterolemia (HeFH)* and at least one of the following criteria: - Fasting LDL-C >190 mg/dL (4.9 mmol/L) at Visit 2 or - Fasting LDL-C >160 mg/dL (4.1 mmol/L) at Visit 2 and either of the following: - Family history of premature cardiovascular disease (CVD) defined as onset of clinical atherosclerotic disease before age 55 in males or age 65 in females or - 2 or more other CVD risk factors (HDL-C 190 mg/dL in an adult; >160 mg/dL in a child =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Any of the following is regarded as a criterion for exclusion from the study: 1. History of statin induced myopathy or serious hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins), including rosuvastatin 2. Fasting TG ³250 mg/dL (2.87 mmol/L) at Visit 2 3. Fasting serum glucose of >180 mg/dL (9.99 mmol/L) or HbA1c >9% at Visit 1 or patients with a history of diabetic ketoacidosis within the past 5 years 4. Uncontrolled hypothyroidism defined as thyroid stimulating hormone (TSH) > 1.5 times the upper limit of normal (ULN) at Visit 1 (Week -6) or patients whose thyroid replacement therapy was initiated or modified within the last 3 months 5. Use of specified disallowed concomitant medications 6. History of alcohol abuse and/or drug abuse 7. Current active liver disease or hepatic dysfunction (excluding a confirmed diagnosis of Gilbert’s disease) as defined by elevations of 1.5 times the ULN for any age in any of the following liver functions tests: ALT, AST, or bilirubin at Visit 1 8. Serum creatine kinase (CK) ³3 times ULN (unless explained by exercise) at Visit 1 9. Estimated GFR by Schwartz formula 12 years of age with testicular volume 97th percentile for age and sex (See Appendix I)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the efficacy of once-daily rosuvastatin in reducing LDL-C in children and adolescents aged 10-17 years with HeFH from baseline (Day 0) to the end of the 12-week double-blind treatment period.;Secondary Objective: 1.The percent change in LDL-C from baseline to Week 6 2.The percent change in HDL-C, TC, TG, non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, ApoB, ApoB/ApoA-1, and ApoA-1 for each assigned dose level from baseline to Week 6, and to the end of the double-blind treatment period as compared to placebo 3.The efficacy of rosuvastatin in achieving the LDL-C goal of <110 mg/dL (percent response rate) after 40 weeks of titration-to-goal dosing. 4.The safety of each dose level by assessing the incidence and severity of adverse events, abnormal serum laboratory values, and rate of discontinuations due to AEs at Week 12 (vs. placebo) and during the 40-week open label treatment 5.The effects on urinary protein excretion and estimated glomerular filtration rate 6.The effect on growth by assessment of height (including linear growth [cm and Standard Deviation Score]) and secondary characteristics of sexual maturation by Tanner Staging at baseline and 52 weeks ;Primary end point(s): The primary efficacy endpoint will be the percent change from the baseline in LDL-C at 12 weeks of treatment for each rosuvastatin dose as compared to placebo. Statistically significant results for any dose (without multiplicity adjustment) will be considered acceptable evidence of efficacy if a trend toward dose response is evident. | — |
Countries
Netherlands, Spain
Outcome results
None listed