NCT01078675

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
315

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Feb 2010

Typical duration for phase_3

Geographic Reach
5 countries

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2010

Completed
24 days until next milestone

First Submitted

Initial submission to the registry

February 25, 2010

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 2, 2010

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2013

Completed
2 years until next milestone

Results Posted

Study results publicly available

February 2, 2015

Completed
Last Updated

April 7, 2015

Status Verified

March 1, 2015

Enrollment Period

3 years

First QC Date

February 25, 2010

Results QC Date

February 6, 2014

Last Update Submit

March 19, 2015

Conditions

Keywords

Familial Hypercholesterolaemiapediatric

Outcome Measures

Primary Outcomes (8)

  • Percent Change From Baseline in LDL-C

    Negative values represent a decrease and positive values represent an increase. In total, 198 patients were treated. One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.

    At Month 3, Month 12 and Month 24

  • Sexual Maturation by Tanner Staging at Baseline

    Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.

    At Baseline

  • Single Dose PK - Cmax

    Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing

    Serial blood samples over 24 hours.

  • Percent Change From Baseline in Height

    One patient received 1 dose of study drug but was not included in the efficacy and safety analyses due to a lack of follow-up data.

    At Month 12 and Month 24

  • Sexual Maturation by Tanner Staging at Month 12

    Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.

    At Baseline

  • Sexual Maturation by Tanner Staging at Month 24

    Tanner stages (I-V) was used to characterize physical development in children and adolescent. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.

    At Baseline

  • Single Dose PK - Tmax

    Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing

    Serial blood samples over 24 hours

  • Single Dose PK - AUC(0-24)

    Serial plasma samples were taken at baseline (Week 0) at: 0.5 hours pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours and on Day 1 at 24 hours after the single 10 mg dosing

    Serial blood samples over 24 hours

Secondary Outcomes (5)

  • 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

    At Month 3, Month 12 and Month 24

  • Change From Baseline in Max and Mean Carotid Intima and Media Wall Thickness (cIMT)

    At Month 12 and Month 24

  • Adverse Events

    2-year study period

  • Total Duration of Exposure

    2-year study period

  • Overal Treatment Adherence

    2-year study period

Study Arms (1)

1

EXPERIMENTAL
Drug: rosuvastatin calcium

Interventions

5 mg, oral, once daily, 24 months

Also known as: Crestor
1

Eligibility Criteria

Age6 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Research Site

Cincinnati, Ohio, United States

Location

Research Site

Leuven, Belgium, Belgium

Location

Research Site

Leuven, Belgium

Location

Research Site

Vancouver, British Columbia, Canada

Location

Research Site

Hamilton, Ontario, Canada

Location

Research Site

Toronto, Ontario, Canada

Location

Research Site

Chicoutimi, Quebec, Canada

Location

Research Site

Québec, Quebec, Canada

Location

Research Site

Amsterdam, Netherlands

Location

Research Site

Groningen, Netherlands

Location

Research Site

Hoorn, Netherlands

Location

Research Site

Leiderdorp, Netherlands

Location

Research Site

Rotterdam, Netherlands

Location

Research Site

Waalwijk, Netherlands

Location

Research Site

Oslo, Norway

Location

Related Publications (3)

  • 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.

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHyperlipoproteinemiasHyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsFluorobenzenesHydrocarbons, FluorinatedHydrocarbons, HalogenatedHydrocarbonsSulfonesSulfur CompoundsPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Niklas Berglind, GPS
Organization
AstraZeneca, R&D, B&I

Study Officials

  • John J.P. Kastelein, MD, PhD

    Chairman, Dept. of Vascular Medicine, Academic Medical Center, Meibergdreef 9

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 25, 2010

First Posted

March 2, 2010

Study Start

February 1, 2010

Primary Completion

February 1, 2013

Study Completion

February 1, 2013

Last Updated

April 7, 2015

Results First Posted

February 2, 2015

Record last verified: 2015-03

Locations