An Study to Evaluate Rosuvastatin in Children and Adolescents With Familial Hypercholesterolaemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01078675
First received: February 25, 2010
Last updated: March 19, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Familial Hypercholesterolaemia
Drug: rosuvastatin calcium
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Percent Change From Baseline in LDL-C [ Time Frame: At Month 3, Month 12 and Month 24 ] [ Designated as safety issue: No ]
    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.

  • Sexual Maturation by Tanner Staging at Baseline [ Time Frame: At Baseline ] [ Designated as safety issue: No ]
    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.

  • Single Dose PK - Cmax [ Time Frame: Serial blood samples over 24 hours. ] [ Designated as safety issue: No ]
    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

  • Percent Change From Baseline in Height [ Time Frame: At Month 12 and Month 24 ] [ Designated as safety issue: No ]
    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.

  • Sexual Maturation by Tanner Staging at Month 12 [ Time Frame: At Baseline ] [ Designated as safety issue: No ]
    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.

  • Sexual Maturation by Tanner Staging at Month 24 [ Time Frame: At Baseline ] [ Designated as safety issue: No ]
    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.

  • Single Dose PK - Tmax [ Time Frame: Serial blood samples over 24 hours ] [ Designated as safety issue: No ]
    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

  • Single Dose PK - AUC(0-24) [ Time Frame: Serial blood samples over 24 hours ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 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 [ Time Frame: At Month 3, Month 12 and Month 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Max and Mean Carotid Intima and Media Wall Thickness (cIMT) [ Time Frame: At Month 12 and Month 24 ] [ Designated as safety issue: No ]
    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.

  • Adverse Events [ Time Frame: 2-year study period ] [ Designated as safety issue: No ]
    Number of participants with Various Categories of AE's. 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.

  • Total Duration of Exposure [ Time Frame: 2-year study period ] [ Designated as safety issue: No ]
    Total duration of exposure was calculated as [last dose date of rosuva - first dose date of rosuva + 1 day]. 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.

  • Overal Treatment Adherence [ Time Frame: 2-year study period ] [ Designated as safety issue: No ]
    Overall adherence rate was calculated as the weighted mean of adherence rates of all consecutive visits after baseline, in which the adherence rate between 2 consecutive visits was a percentage of the number of rosuvastatin taken divided by duration of exposure. 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.


Enrollment: 315
Study Start Date: February 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: rosuvastatin calcium
5 mg, oral, once daily, 24 months
Other Name: Crestor
Drug: rosuvastatin calcium
10 mg, oral, once daily, 24 months
Other Name: Crestor
Drug: rosuvastatin calcium
20 mg, oral, once daily, 24 months
Other Name: Crestor

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01078675

Locations
United States, Ohio
Research Site
Cincinnati, Ohio, United States
Belgium
Research Site
Leuven, Belgium
Canada, British Columbia
Research Site
Vancouver, British Columbia, Canada
Canada, Ontario
Research Site
Hamilton, Ontario, Canada
Research Site
Toronto, Ontario, Canada
Canada, Quebec
Research Site
Chicoutimi, Quebec, Canada
Canada
Research Site
Quebec, Canada
Netherlands
Research Site
Amsterdam, Netherlands
Research Site
Groningen, Netherlands
Research Site
Hoorn, Netherlands
Research Site
Leiderdorp, Netherlands
Research Site
Rotterdam, Netherlands
Research Site
Waalwijk, Netherlands
Norway
Research Site
Oslo, Norway
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: John J.P. Kastelein, MD, PhD Chairman, Dept. of Vascular Medicine, Academic Medical Center, Meibergdreef 9
  More Information

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01078675     History of Changes
Other Study ID Numbers: D3561C00002
Study First Received: February 25, 2010
Results First Received: February 6, 2014
Last Updated: March 19, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Familial Hypercholesterolaemia
pediatric

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Dyslipidemias
Genetic Diseases, Inborn
Hyperlipidemias
Hyperlipoproteinemias
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Metabolism, Inborn Errors
Calcium, Dietary
Rosuvastatin
Anticholesteremic Agents
Antimetabolites
Bone Density Conservation Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015