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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02434497
• Date of registration: 07/04/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: A Study to Evaluate the Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia
• Scientific 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)
• Date of first enrolment: June 6, 2015
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02434497
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Belgium, Canada, Denmark, Israel, Malaysia, Taiwan

Key inclusion & exclusion 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.



Age minimum: 6 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Homozygous Familial Hypercholesterolemia (HoFH)

Intervention(s)

Drug: Rosuvastatin 20mg

Primary Outcome(s)

Safety and Tolerability in Terms of Abnormal Physical Exams, Cardiovascular [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Physical Exams, Head and Neck [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Physical Exams, General Appearance [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular Volume (fL) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Bicarbonate (Mol/L) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Sodium (mmol/L) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular Volume (fL) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Ketones [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Protein [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Physical Exams, Skin [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Albumin (g/dL) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Vital Signs [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal ECG, Abnormalities [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Erythrocytes (10^12/L) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Basophils/Leukocytes (%) >Upper Limite of Normal (ULN) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Creatine Kinase (U/L) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Erythrocytes (10^12/L) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Alanine Aminotransferase (U/L) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Leukocytes >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Monocytes/Leukocytes (%) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Protein (g/dL) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Physical Exams, Musculoskeletal/Extremities [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Aspartate Aminotransferase (U/L) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Chloride (mmol/L) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Bicarbonate (Mol/L) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Phosphate (mg/dL) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular HGB Concentration (g/dL) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Hematocrit (%) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Hemoglobin (g/dL) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lymphocytes/Leukocytes (%) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Platelets (10^9/L) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormalitites in Sexual Maturation [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Growth, Height [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Number of Participants Who Had Adverse Events, Discontinuations Due to Adverse Events [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Blood Urea Nitrogen (mg/dL) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Ery. Mean Corpuscular HGB (pg) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Urate (mg/dL) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Growth, Weight [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Glucose (mg/dL) >ULN [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Urine Laboratory Values, Urine Occult Blood [Time Frame: 96 weeks]

The Number of Participants Who Experianced Adverse Events and Serious Adverse Events [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lactate Dehydrogenase (U/L) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Abnormal Serum Laboratory Values, Lymphocytes/Leukocytes (%) [Time Frame: 96 weeks]

Safety and Tolerability in Terms of Growth, Height SD-score (or Z-score) [Time Frame: 96 weeks]

Secondary Outcome(s)

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]

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]

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]

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]

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]

Pharmacokinetic Profile in Terms of Trough Concentrations in Pediatric HoFH Taking a Daily Dose of Rosuvastatin 40mg [Time Frame: Up to 22 months]

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]

Percent Change in ApoB From End of Placebo of D3561C00004 to the End of D356NC00001, Repeated Measures Analysis [Time Frame: Up to 22 months]

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]

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]

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]

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]

Secondary ID(s)

D356NC00001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/02/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02434497