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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- LDL-Cholesterol (mg/dL)
研究概览
简要总结
The purpose of the study is to establish the efficacy, safety and tolerability of rosuvastatin in children and adolescents with homozygous familial hypercholesterolemia.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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:
- •Tendinous and/or cutaneous xanthoma prior to 10 years of age; or
- •Documentation of HoFH in both parents by:
- •genetic and/or
- •clinical criteria
- •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
- •Willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.
- •Exclusion Criteria
- •History of statin inducted myopathy or serious hypersensitivity reaction to other HMG CoA reductase inhibitors (statins), including rosuvastatin, at Visit
- •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.
- •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
- •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.
- •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.
排除标准
- 未提供
研究组 & 干预措施
Rosuvastatin
6-week treatment period, and after crossover finished a 12-week efficacy maintenance phase for all patients
干预措施: Rosuvastatin 20mg (Drug)
Placebo
6 weeks treatment during crossover
干预措施: Placebo (Drug)
结局指标
主要结局
LDL-Cholesterol (mg/dL)
时间窗: Samples taken on Day 42 (week 6) and on day 84 (week 12)
Change in low density lipoprotein cholesterol (LDL C) following 6 weeks of rosuvastatin 20 mg compared to 6 weeks of placebo treatment
LDL-Cholesterol (mmol/L)
时间窗: Samples taken on Day 42 (week 6) and on day 84 (week 12)
Change in low density lipoprotein cholesterol (LDL C) following 6 weeks of rosuvastatin 20 mg compared to 6 weeks of placebo treatment
次要结局
- TC (mg/dL)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- LDL-C From End of Placebo (mg/dL)(Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24))
- LDL-C From End of Placebo (mmol/L)(Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24))
- ApoB (mg/dL)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- TC (mmol/L)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- Non-HDL C (mg/dL)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- Non-HDL C (mmol/L)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- ApoB (g/L)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- HDL-C (mg/dL)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- HDL-C (mmol/L)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- LDL-C, Not on Apheresis (mg/dL)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- LDL-C, Not on Apheresis (mmol/L)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- Trough Concentrations(Samples taken 24 hours post-dose at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18))
- Adverse Events(From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening))
- Non-HDL C/HDL C(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- ApoB/ApoA(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- Abnormal Vital Signs(From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening))
- AE's Leading to Discontinuation(From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening))
- Abnormal Serum Levels(From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening))
- Height(Week 0 (start of cross-over), weeks 6, week 12 and week 18)
- Height Z-score(Week 0 (start of cross-over), weeks 6, week 12 and week 18)
- Weight(Week 0 (start of cross-over), weeks 6, week 12 and week 18)
- Tanner Stage(Week 0 (start of cross-over))
- TG (mmol/L)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- TC/HDL C(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- TG (mg/dL)(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- LDL C/HDL C(Samples taken at Day 42 (week 6) and Day 84 (week 12))
- Physical Exam Abnormalitites(Screening, Week 0, week 6, week 12 and week 18, week 24)
- Urinalysis Abnormalitites(Week 0, week 6, week 12 and week 18)
- ECG Abnormalities(Week 0)