A study to evaluate the effect of Rosuvastatin on fatty acids in Children and Adolescents with Homozygous Familial Hypercholesterolemia

• Register: EUCTR
• Last refreshed on: 14 September 2015
• Main ID: EUCTR2014-000972-24-SE
• Date of registration: 30/06/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A study to evaluate the effect of Rosuvastatin on fatty acids in Children and Adolescents with Homozygous Familial Hypercholesterolemia
• Scientific 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) - HYDRA
• Date of first enrolment: 20/08/2014
• Target sample size: 25
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000972-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Belgium, Czech Republic, Denmark, Germany, Hong Kong, Israel, Netherlands, Norway, South Africa, Sweden, Taiwan, United Kingdom, United States

Contacts

• Name: Information Centre
• Affiliation: AstraZeneca

• Name: Information Centre
• Affiliation: AstraZeneca

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 [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;
2.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:
oTendinous and/or cutaneous xanthoma prior to 10 years of age; or
oDocumentation 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.Willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.

Are the trial subjects under 18? yes
Number of subjects for this age range: 25
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.History of statin inducted myopathy or serious hypersensitivity reaction to other HMG CoA reductase inhibitors (statins), including rosuvastatin, at Visit 1;
2.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;
3.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;
4.Current active liver disease or hepatic dysfunction (except a confirmed diagnosis of Gilbert’s disease) as defined as elevations of 1.5 times the ULN for any age in any of the following liver function tests at Visit 1: ALT, AST, or bilirubin;
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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Hypercholesterolemia - The current trial will study children with Homozygous Familial Hypercholesterolemia (HoFH)
MedDRA version: 17.1 Level: LLT Classification code 10054380 Term: Familial hypercholesterolemia System Organ Class: 100000004850

Intervention(s)

Trade Name: Crestor Tablets (calcium rosuvastatin) Film-Coated tablets
Product Name: Crestor
Product Code: ZD4522
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: calcium rosuvastatin
CAS Number: 147098-20-2
Current Sponsor code: ZD4522
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Samples taken Day 42 (week 6), Day 84 (week 12)

Main Objective: To assess the efficacy of rosuvastatin 20 mg on low density lipoprotein cholesterol (LDL C), compared to placebo, after 6 weeks of treatment in pediatric patients with Homozygous Familial Hypercholesterolemia (HoFH)

Secondary Objective: To assess the efficacy of rosuvastatin 20 mg on LDL C, compared to placebo, after 6 weeks of treatment in pediatric patients with HoFH not treated with apheresis
To assess the efficacy of rosuvastatin 20 mg on lipid parameters other than LDL C, compared to placebo, after 6 weeks of treatment in pediatric patients with HoFH
To assess the longitudinal profile of LDL C during treatment with rosuvastatin 20 mg
To characterize the trough plasma exposure of rosuvastatin in pediatric patients with HoFH

Primary end point(s): "Describe efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment

Secondary Outcome(s)

Secondary end point(s): 1 Describe 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
2 Describe efficacy in terms of High density lipoprotein cholesterol (HDL C), total cholesterol (TC), triglyceride (TG), non-HDL C, LDL-C/HDL C, TC/HDL C, non-HDL-C/HDL C, apolipoprotein B (ApoB), ApoB/apolipoprotein A 1 (ApoA 1) and ApoA 1 following 6 weeks of treatment with rosuvastatin 20 mg or placebo
3 Describe the longitudinal profile of LDL C as a change in LDL C from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg
4, Describe the pharmacokinetic profile in terms of trough concentrations

Safety
Adverse events, including:
• The frequency and severity of adverse events
• Rate of discontinuations due to adverse
events
• Abnormal serum and urine laboratory values,
ECGs, physical examinations, and vital signs
Assessments of growth, including height (linear
growth [cm and standard deviation (SD) score]),
weight, and secondary characteristics of sexual
maturation by Tanner stage performed at the
beginning of the lead-in phase (Visit 2) and at Visit 7

Timepoint(s) of evaluation of this end point: 1 and 2: Samples taken Day 42 (week 6), Day 84 (week 12)

3. Samples taken Day 42 (week 6), Day 84 (week 12), Day 126 (week 18), Day 168 (week 24)
4. Samples taken Day 126 (week 18), Day 168 (week 24)

Safety
From screeing up to week 24

Secondary ID(s)

D3561C00004

Source(s) of Monetary Support

AstraZeneca AB