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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Familial Hypercholesterolaemia

Intervention / Treatment
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* Drug: rosuvastatin calcium
* Drug: rosuvastatin calcium
* Drug: rosuvastatin calcium


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: rosuvastatin calcium<br>* 5 mg, oral, once daily, 24 months<br>* Other names: Crestor;Drug: rosuvastatin calcium<br>* 10 mg, oral, once daily, 24 months<br>* Other names: Crestor;Drug: rosuvastatin calcium<br>* 20 mg, oral, once daily, 24 months<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 
| Change From Baseline in Max and Mean Carotid Intima and Media Wall Thickness (cIMT) | 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 | 
| Adverse Events | 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. | 2-year study period | 
| Total Duration of Exposure | 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. | 2-year study period | 
| Overal Treatment Adherence | 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. | 2-year study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Familial Hypercholesterolaemia, pediatric