Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02434497
Recruitment Status : Completed
First Posted : May 5, 2015
Results First Posted : February 27, 2018
Last Update Posted : February 27, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
The purpose of the study is to evaluate the safety of Rosuvastatin in Children and Adolescents with Homozygous Familial Hypercholesterolemia.

Condition or disease Intervention/treatment Phase
Homozygous Familial Hypercholesterolemia (HoFH) Drug: Rosuvastatin 20mg Phase 3

Detailed Description:

This is a long-term extension (LTE) to the randomized, double-blind, cross-over study of rosuvastatin 20 mg once daily (QD) versus placebo QD in children and adolescents (aged from 6 to <18 years) with homozygous familial hypercholesterolemia (HoFH) (Study D3561C00004).

The study is designed to assess the long-term safety and tolerability of rosuvastatin 20 mg in pediatric patients with HoFH.

In this study all patients will receive rosuvastatin 20 mg QD. Investigators will also be permitted to titrate the dose of rosuvastatin from 20 to 40 mg per day if they feel it is warranted to more aggressively treat patients' elevated LDL-C levels. This up-titration will not be permitted in Asian patients. Pharmacokinetic data of the trough plasma exposure of rosuvastatin will also be assessed for the pediatric patients with HoFH taking a daily dose of rosuvastatin 40 mg.

The primary outcome measures to be assessed include 1) Adverse events, including:

  • The frequency and severity of adverse events,
  • Rate of discontinuations due to adverse events,
  • Abnormal serum and urine laboratory values, electrocardiograms (ECGs), physical examinations, and vital signs; and 2) Assessments of growth.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Long-Term Extension to the 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)
Actual Study Start Date : June 6, 2015
Actual Primary Completion Date : November 17, 2016
Actual Study Completion Date : November 17, 2016


Arm Intervention/treatment
Experimental: Single Arm
One treatment period for all patients (<1 year and 10 months), with the possibility to up-titrate dose to 40 mg of rosuvastatin for non-Asian patients.
Drug: Rosuvastatin 20mg
Active drug 1 or 2 tablets will be taken taken orally, QD, either in the morning or in the evening




Primary Outcome Measures :
  1. The Number of Participants Who Experianced Adverse Events and Serious Adverse Events [ Time Frame: 96 weeks ]
  2. Safety and Tolerability in Terms of Number of Participants Who Had Adverse Events, Discontinuations Due to Adverse Events [ Time Frame: 96 weeks ]
  3. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Basophils/Leukocytes (%) >Upper Limite of Normal (ULN) [ Time Frame: 96 weeks ]
  4. Safety and Tolerability in Terms of Growth, Height [ Time Frame: 96 weeks ]
  5. Safety and Tolerability in Terms of Abnormalitites in Sexual Maturation [ Time Frame: 96 weeks ]
  6. Safety and Tolerability in Terms of Growth, Height SD-score (or Z-score) [ Time Frame: 96 weeks ]
    Height z-score is a dimensionless quantity derived by subtracting the population mean from the individual raw score, and then deviding the difference by the pouulation SD of the reference population. This indicates how many SDs and observation is above or below the general population mean.

  7. Safety and Tolerability in Terms of Growth, Weight [ Time Frame: 96 weeks ]
  8. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Alanine Aminotransferase (U/L) >ULN [ Time Frame: 96 weeks ]
  9. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Albumin (g/dL) >ULN [ Time Frame: 96 weeks ]
  10. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Aspartate Aminotransferase (U/L) >ULN [ Time Frame: 96 weeks ]
  11. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Bicarbonate (Mol/L) <LLN [ Time Frame: 96 weeks ]
  12. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Bicarbonate (Mol/L) >ULN [ Time Frame: 96 weeks ]
  13. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular HGB Concentration (g/dL) <LLN [ Time Frame: 96 weeks ]
  14. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular HGB (pg) <LLN [ Time Frame: 96 weeks ]
  15. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular Volume (fL) <LLN [ Time Frame: 96 weeks ]
  16. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular Volume (fL) >ULN [ Time Frame: 96 weeks ]
  17. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Erythrocytes (10^12/L) <LLN [ Time Frame: 96 weeks ]
  18. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Erythrocytes (10^12/L) >ULN [ Time Frame: 96 weeks ]
  19. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Hematocrit (%) <LLN [ Time Frame: 96 weeks ]
  20. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Hemoglobin (g/dL) <LLN [ Time Frame: 96 weeks ]
  21. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Leukocytes >ULN [ Time Frame: 96 weeks ]
  22. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lymphocytes/Leukocytes (%) <LLN [ Time Frame: 96 weeks ]
  23. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lymphocytes/Leukocytes (%) >ULN [ Time Frame: 96 weeks ]
  24. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Monocytes/Leukocytes (%) >ULN [ Time Frame: 96 weeks ]
  25. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Platelets (10^9/L) >ULN [ Time Frame: 96 weeks ]
  26. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Blood Urea Nitrogen (mg/dL) <LLN [ Time Frame: 96 weeks ]
  27. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Chloride (mmol/L) >ULN [ Time Frame: 96 weeks ]
  28. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Creatine Kinase (U/L) >ULN [ Time Frame: 96 weeks ]
  29. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Glucose (mg/dL) >ULN [ Time Frame: 96 weeks ]
  30. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lactate Dehydrogenase (U/L) <LLN [ Time Frame: 96 weeks ]
  31. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Phosphate (mg/dL) >ULN [ Time Frame: 96 weeks ]
  32. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Protein (g/dL) >ULN [ Time Frame: 96 weeks ]
  33. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Sodium (mmol/L) <LLN [ Time Frame: 96 weeks ]
  34. Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Urate (mg/dL) >ULN [ Time Frame: 96 weeks ]
  35. Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Ketones [ Time Frame: 96 weeks ]
  36. Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Occult Blood [ Time Frame: 96 weeks ]
  37. Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Protein [ Time Frame: 96 weeks ]
  38. Safety and Tolerability in Terms of Abnormal ECG, Abnormalities [ Time Frame: 96 weeks ]
  39. Safety and Tolerability in Terms of Abnormal Physical Exams, Cardiovascular [ Time Frame: 96 weeks ]
  40. Safety and Tolerability in Terms of Abnormal Physical Exams, General Appearance [ Time Frame: 96 weeks ]
  41. Safety and Tolerability in Terms of Abnormal Physical Exams, Head and Neck [ Time Frame: 96 weeks ]
  42. Safety and Tolerability in Terms of Abnormal Physical Exams, Musculoskeletal/Extremities [ Time Frame: 96 weeks ]
  43. Safety and Tolerability in Terms of Abnormal Physical Exams, Skin [ Time Frame: 96 weeks ]
  44. Safety and Tolerability in Terms of Abnormal Vital Signs [ Time Frame: 96 weeks ]

Secondary Outcome Measures :
  1. Percent Change in LDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  2. Percent Change in HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  3. Percent Change in Total Cholesterol (TC) From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  4. Percent Change in Triglycerides (TG) From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  5. Percent Change in Non-HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  6. Percent Change in LDL-C/HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  7. Percent Change in TC/HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  8. Percent Change in Non-HDL-C/HDL-C From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  9. Percent Change in ApoB From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  10. Percent Change in ApoA-1 From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  11. Percent Change in ApoB/ApoA-1 From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [ Time Frame: Up to 22 months ]
  12. Pharmacokinetic Profile in Terms of Trough Concentrations in Pediatric HoFH Taking a Daily Dose of Rosuvastatin 40mg [ Time Frame: Up to 22 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 [IEC] according to local regulations and guidelines). Study D3561C00004 participants who have had their 18th birthday (adults) will be required to provide written informed consent. Communication should take place 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 who were aged 6 to <18 years at the onset of Study D3561C00004 (even if they had their 18th birthday during that study) with:

    • 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 TG <400 mg/dL (4.5 mmol/L) and at least 1 of the following criteria:

      • Tendinous and/or cutaneous xanthoma prior to 10 years of age; or
      • 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. Were taking study drug at the end of Study D3561C00004 and are 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 of Study D3561C00004.
  2. Fasting serum glucose of >9.99 mmol/L (180 mg/dL) or glycosylated hemoglobin >9% during Study D3561C00004 or patients with a history of diabetic ketoacidosis within the past year.
  3. Uncontrolled hypothyroidism defined as thyroid stimulating hormone >1.5 times the upper limit of normal (ULN) at any time during Study D3561C00004.
  4. Evidence of active liver disease or hepatic dysfunction (except a confirmed diagnosis of Gilbert's disease) as defined as non-transient elevations of ALT or AST elevations ≥3 times the ULN or non-transient total bilirubin ≥2 times the ULN during the Study D3561C00004.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02434497


Locations
Layout table for location information
Belgium
Research Site
Brussels (Woluwé-St-Lambert), Belgium, 1200
Canada, Quebec
Research Site
Chicoutimi, Quebec, Canada, G7H 7K9
Denmark
Research Site
Copenhagen, Denmark, DK-2100
Israel
Research Site
Halfa, Israel, 31096
Malaysia
Research Site
Kubang Kerian, Malaysia, 16150
Taiwan
Research Site
Taipei City, Taiwan, 11217
Sponsors and Collaborators
AstraZeneca
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02434497    
Other Study ID Numbers: D356NC00001
First Posted: May 5, 2015    Key Record Dates
Results First Posted: February 27, 2018
Last Update Posted: February 27, 2018
Last Verified: February 2018
Keywords provided by AstraZeneca:
LDL-C
HoFH
Hyperlipidemia
Additional relevant MeSH terms:
Layout table for MeSH terms
Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Rosuvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors