Clinical trial NCT01078675: An Study to Evaluate Rosuvastatin in Children and Adolescents With Familial Hypercholesterolaemia
Official title: An Efficacy and 2-Year Safety Study of Open-label Rosuvastatin in Children and Adolescents (Aged From 6 to Less Than 18 Years) With Familial Hypercholesterolaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Familial Hypercholesterolaemia
Keywords: Familial Hypercholesterolaemia
pediatric
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-03-02
Enrollment: 315
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is being carried out to see if the study medication, rosuvastatin, is effective in treating familial hypercholesterolaemia in children and adolescents, and to determine the long term (over 2 years) safety, tolerability and efficacy of the study medication in these patients.

This study will also measure levels of drug in the blood and see how well it is tolerated. This is known as pharmacokinetic (PK) analysis.

At baseline only a small number of patients will participate in a single dose PK phase over 24 hours.

In order to see if this medication works, a control group of healthy siblings will help the researchers to compare certain results.


Eligibility criteria: Inclusion Criteria:

* children and adolescents (aged 6 to less than 18 years) with Familial Hypercholesterolaemia
* Patients aged between 6 and less than 10 years of age must not be taking a statin medicine

Exclusion Criteria:

* History of muscle or sensitivity reactions to any statin medicines
* Current active liver disease or dysfunction (except a confirmed diagnosis of Gilbert's disease)

Primary outcomes:
measure: Percent Change From Baseline in LDL-C
timeFrame: At Month 3, Month 12 and Month 24
measure: Sexual Maturation by Tanner Staging at Baseline
timeFrame: At Baseline
measure: Single Dose PK - Cmax
timeFrame: Serial blood samples over 24 hours.
measure: Percent Change From Baseline in Height
timeFrame: At Month 12 and Month 24
measure: Sexual Maturation by Tanner Staging at Month 12
timeFrame: At Baseline
measure: Sexual Maturation by Tanner Staging at Month 24
timeFrame: At Baseline
measure: Single Dose PK - Tmax
timeFrame: Serial blood samples over 24 hours
measure: Single Dose PK - AUC(0-24)
timeFrame: Serial blood samples over 24 hours
Secondary outcomes:
measure: Percent Change From Baseline in HDL-C, TC, TG, Non-HDL-C, LDL-C/HDL-C, TC/HDL-C, Non HDL C/HDL-C, ApoB, ApoA-1, and ApoB/ApoA-1
timeFrame: At Month 3, Month 12 and Month 24
measure: Change From Baseline in Max and Mean Carotid Intima and Media Wall Thickness (cIMT)
timeFrame: At Month 12 and Month 24
measure: Adverse Events
timeFrame: 2-year study period
measure: Total Duration of Exposure
timeFrame: 2-year study period
measure: Overal Treatment Adherence
timeFrame: 2-year study period
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Leuven
country: Belgium
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Hoorn
country: Netherlands
facility: Research Site
city: Leiderdorp
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Waalwijk
country: Netherlands
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
Study officials:
affiliation: Chairman, Dept. of Vascular Medicine, Academic Medical Center, Meibergdreef 9
name: John J.P. Kastelein, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Braamskamp MJAM, Langslet G, McCrindle BW, Cassiman D, Francis GA, Gagne C, Gaudet D, Morrison KM, Wiegman A, Turner T, Miller E, Kusters DM, Raichlen JS, Martin PD, Stein EA, Kastelein JJP, Hutten BA. Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia: The CHARON Study (Hypercholesterolemia in Children and Adolescents Taking Rosuvastatin Open Label). Circulation. 2017 Jul 25;136(4):359-366. doi: 10.1161/CIRCULATIONAHA.116.025158. Epub 2017 Jun 7.
citation: Kusters DM, Wiegman A, Kastelein JJ, Hutten BA. Carotid intima-media thickness in children with familial hypercholesterolemia. Circ Res. 2014 Jan 17;114(2):307-10. doi: 10.1161/CIRCRESAHA.114.301430. Epub 2013 Nov 5.
citation: Tolani S, Pagler TA, Murphy AJ, Bochem AE, Abramowicz S, Welch C, Nagareddy PR, Holleran S, Hovingh GK, Kuivenhoven JA, Tall AR. Hypercholesterolemia and reduced HDL-C promote hematopoietic stem cell proliferation and monocytosis: studies in mice and FH children. Atherosclerosis. 2013 Jul;229(1):79-85. doi: 10.1016/j.atherosclerosis.2013.03.031. Epub 2013 Apr 19.