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Completed

NCT Number: NCT02226198

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

The purpose of the study is to establish the efficacy, safety and tolerability of rosuvastatin in children and adolescents with homozygous familial hypercholesterolemia.

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Key information

Conditions

Homozygous Familial Hypercholesterolemia (HoFH) Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dyslipidemias Genetic Diseases, Inborn Homozygous Familial Hypercholesterolemia Hyperlipidemias Hyperlipoproteinemia Type II Hyperlipoproteinemias Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases

Age range

6 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Brussels (Woluwé-St-Lambert), Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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 1.
  • 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 2.
  • 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.

Treatment and study plan

Rosuvastatin 20mg

Drug

Active drug will be taken taken orally, QD, either in the morning or in the evening

Placebo

Drug

Will be taken taken orally, QD, either in the morning or in the evening

Primary outcomes

  1. LDL-Cholesterol (mg/dL)

    Time frame: 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

  2. LDL-Cholesterol (mmol/L)

    Time frame: 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

Secondary outcomes

  1. TC (mg/dL)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of total cholesterol (TC)

  2. TC (mmol/L)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of total cholesterol (TC)

  3. Non-HDL C (mg/dL)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C)

  4. Non-HDL C (mmol/L)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C)

  5. ApoB (mg/dL)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of apolipoprotein B (ApoB)

  6. ApoB (g/L)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of apolipoprotein B (ApoB)

  7. HDL-C (mg/dL)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of high density lipoprotein cholesterol (HDL C)

  8. HDL-C (mmol/L)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of high density lipoprotein cholesterol (HDL C)

  9. LDL-C, Not on Apheresis (mg/dL)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis

  10. LDL-C, Not on Apheresis (mmol/L)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis

  11. LDL-C From End of Placebo (mg/dL)

    Time frame: Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)

    Change in low density lipoprotein cholesterol (LDL C) from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg

  12. LDL-C From End of Placebo (mmol/L)

    Time frame: Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)

    Change in low density lipoprotein cholesterol (LDL C) from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg

  13. Trough Concentrations

    Time frame: Samples taken 24 hours post-dose at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18)

    Pharmacokinetic profile in terms of trough concentrations. Cross-over phase results based on measurements taken after 6 weeks active treatment (rosuvastatin) in the cross-over phase. Maintenance phase results based on measurements taken after 6 weeks active treatment (rosuvastatin) in the maintenance phase.

  14. Adverse Events

    Time frame: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

    Safety and tolerability will be described in terms of frequency and severity of adverse events

  15. AE's Leading to Discontinuation

    Time frame: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

    Safety and tolerability will be described in terms of rate of discontinuations due to adverse events

  16. Abnormal Serum Levels

    Time frame: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

    Safety and tolerability will be described in terms of abnormal serum laboratory values. The reported parameters are not the only ones measured, but rather those for which abnormailities were found

  17. Height

    Time frame: Week 0 (start of cross-over), weeks 6, week 12 and week 18

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

  18. Height Z-score

    Time frame: Week 0 (start of cross-over), weeks 6, week 12 and week 18

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

  19. Weight

    Time frame: Week 0 (start of cross-over), weeks 6, week 12 and week 18

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

  20. Tanner Stage

    Time frame: Week 0 (start of cross-over)

    Stages for fem (Pubic hair, Breasts):

    • (Preadol,Preadol)
    • (Sparse, lightly pigmented, medial border of labia,Breast and papilla elevated as small mound; areolar diam incr)
    • (Darker, beginning to curl, incr amount, Breast and areola enlarged, no contour separation)
    • (Course, curly, abundant but less amount in adult,Areola and papilla form secondary mound)
    • (Adult fem triangle, spread to medial surface of thighs,Mature, nipple projects, areola part of general breast contour) For males (Pubic hair, Penis, Testes)

    1=(None,Preadol,Preadol) 2=(Scanty, long, light pigm,Slight enl,Enl scrotum, pink texture alt) 3=(Darker, starts to curl, small amount,Longer,Larger) 4=(Resembles adult type, but less in quant; course, curly,Larger; glans and breadth increased in size,Larger, scrotum dark) 5=(Adult distr, spread to medial thighs,Adult size,Adult size). Progr at a normal rate is preferred. Regr is not preferred.

  21. TG (mg/dL)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of triglycerides (TG)

  22. TG (mmol/L)

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of triglycerides (TG)

  23. LDL C/HDL C

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of low density lipoprotein cholesterol (LDL C) / high density lipoprotein cholesterol (HDL C)

  24. TC/HDL C

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of total cholesterol (TC) / high density lipoprotein cholesterol (HDL C)

  25. Non-HDL C/HDL C

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C) / HDL C

  26. ApoB/ApoA

    Time frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)

    Efficacy in terms of apolipoprotein B (ApoB) / apolipoprotein A (ApoA)

  27. Urinalysis Abnormalitites

    Time frame: Week 0, week 6, week 12 and week 18

    Safety and tolerability will be described in terms of abnormal urine laboratory values

  28. ECG Abnormalities

    Time frame: Week 0

    Safety and tolerability will be described in terms of abnormal electro cardio gram (ECG)

  29. Physical Exam Abnormalitites

    Time frame: Screening, Week 0, week 6, week 12 and week 18, week 24

    Safety and tolerability will be described in terms of abnormal physical examinations. Only parameters for which abnormalities were found are reported.

  30. Abnormal Vital Signs

    Time frame: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

    Safety and tolerability will be described in terms of abnormal vital signs

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

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)

Acronym: HYDRA

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Aug 27, 2014
Registry last updated
Jul 4, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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