Atorvastatin Three Year Pediatric Study

Study Overview
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Brief Summary
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The purpose of this study is to characterize three year descriptive growth and development (ie, height, weight, body mass index, Tanner Stage) and efficacy of cholesterol reduction in pediatric subjects with Heterozygous Familial Hypercholesterolemia receiving atorvastatin treatment.

Official Title
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A Three Year, Prospective, Open-label, Study To Evaluate Clinical Efficacy, Safety And Tolerability Of Atorvastatin In Children And Adolescents With Heterozygous Familial Hypercholesterolemia

Conditions
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Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heterozygous familial hypercholesterolemia, ages 6-15, LDL greater than 4 mmol/l Exclusion Criteria: Active liver disease or hepatic dysfunction, or persistent elevations of serum transaminases exceeding three times the upper limit of normal (ULN). Female of childbearing potential who is not using adequate contraceptive measures or any female who is pregnant or breastfeeding. Any female who becomes pregnant during study participation will be immediately discontinued from treatment and counseled appropriately about the in utero exposure. Known hypersensitivities to HMG-CoA reductase inhibitors

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 15 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>All subjects will be treated with atorvastatin | Drug: atorvastatin<br>* Atorvastatin tablets or chewable tablets, 5, 10, 20, 40 mg strengths, once daily, for three years (an 80 mg maximum daily dose is delivered by taking two 40 mg strengths, once daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low Density Lipoprotein Cholesterol (LDL-C; Millimoles Per Liter [mMol/L]) During the Study | Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36 (or early termination [ET]) | 
| Percent Change From Baseline in LDL-C | Assessments were performed in the fasting state (minimum 10-hour fast). | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36 (or ET) | 
| High-Density Lipoprotein Cholesterol (HDL-C; mMol/L) During the Study | Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in HDL-C | Assessments were performed in the fasting state (minimum 10-hour fast). | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Total Cholesterol (mMol/L) During the Study | Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Total Cholesterol | Assessments were performed in the fasting state (minimum 10-hour fast). | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Trigylcerides (mMol/L) During the Study | Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Trigylcerides | Assessments were performed in the fasting state (minimum 10-hour fast). | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Very Low-Density Lipoprotein (VLDL; mMol/L) During the Study | Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in VLDL | Assessments were performed in the fasting state (minimum 10-hour fast). | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Apoliprotein A-1 (Apo A-1; Grams Per Liter [g/L]) During the Study | Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Apo A-1 | Assessments were performed in the fasting state (minimum 10-hour fast). | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Apoliprotein B (Apo B; g/L) During the Study | Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Apo B | Assessments were performed in the fasting state (minimum 10-hour fast). | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Number of Participants With Shift From Baseline in Tanner_Stage by Timepoint and Baseline Tanner_Stage | Tanner_Stage was assessed based on 2 components by gender, pubic hair and breasts for females and pubic hair and genitalia for males. If these values of components were not same, then the Tanner_Stage had the higher value of 2 components for each gender by visit. | Baseline, Months 6, 12, 18, 24, 30, and 36/ET | 
| Height (Centimeters [cm]) During the Study: Males | Investigator assessment of height changes during the study. Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Height: Males | Investigator assessment of height changes during the study. | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Height (cm) During the Study: Females | Investigator assessment of height changes during the study. Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Height: Females | Investigator assessment of height changes during the study. | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Weight (Kilograms [kg]) During the Study: Males | Investigator assessment of weight changes during the study. Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Weight: Males | Investigator assessment of weight changes during the study. | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Weight (kg) During the Study: Females | Investigator assessment of weight changes during the study. Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Weight: Females | Investigator assessment of weight changes during the study. | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Body Mass Index (BMI in kg Per Square Meter [kg/m^2]) During the Study: Males | Investigator assessment of BMI changes during the study. Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in BMI: Males | Investigator assessment of BMI changes during the study. | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| BMI (kg/m^2) During the Study: Females | Investigator assessment of BMI changes during the study. Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in BMI: Females | Investigator assessment of BMI changes during the study. | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Age (Years) During the Study: Males | Investigator assessment of age during the study. Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Age: Males | Investigator assessment of age during the study. | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Age (Years) During the Study: Females | Investigator assessment of age during the study. Change from baseline was also determined. | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in Age: Females | Investigator assessment of age during the study. | Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET | 
| Flow-Mediated Dilatation (FMD) During the Study | Percent (%) FMD was calculated as (hyperemic diameter minus resting diameter) divided by the resting diameter multiplied by 100. Change from baseline was also determined. | Baseline, Months 6, 12, 18, 24, 30 and 36/ET | 
| Percent Change From Baseline in FMD | Percent (%) FMD was calculated as (hyperemic diameter minus resting diameter) divided by the resting diameter multiplied by 100. | Months 6, 12, 18, 24, 30 and 36/ET | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Overall Expected Maturation and Development Consistent With Expectations as Assessed by the Investigator |  | Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36 (or early termination) | 
| Percentage of Participants by Study Drug Compliance Category | Compliance to study drug was categorized as <80%, 80% - 120%, and greater than (>) 120%. | Months 1, 2, 3, 6, 12, 18, 24, 30, and 36 (or early termination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric heterozygous familial hypercholesterolemia