Atorvastatin Three Year Pediatric Study

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

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.

Study Overview

• Status: Completed
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Drug: atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc / Pediatrie generale
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven / Center for Metabolic Diseases
• Canada
  • Quebec, Canada, G1V 4M6
    • Clinique des maladies lipidiques de Quebec
  • Quebec
    • Sainte-Foy,, Quebec, Canada, G1V 4M6
      • Clinique des Maladies Lipidiques de Quebec Inc
• Germany
  • Berlin, Germany, 13353
    • Charité Campus Virchow-Klinikum
  • Freiburg, Germany, 79098
    • Augenaerztliche Gemeinschaftspraxis
• Greece
  • Athens, Greece, 115 27
    • 1st Pediatrics Clinic , University of Athens, Agia Sofia Hospital
• Hungary
  • Budapest, Hungary, H-1094
    • Semmelweis Medical University
  • Szekesfehervar, Hungary, 8003
    • Fejer Megyei Szent Gyorgy Korhaz
• Italy
  • Palermo, Italy, 90127
    • Dipartimento di Medicina Clinica e delle Patologie Emergenti-University Hospital of Palermo
  • Roma, Italy, 00161
    • Dipartimento di Clinica e Terapia Medica, Università degli Studi di Roma La Sapienza
• Norway
  • Oslo, Norway, 0027
    • Rikshospitalet Lipidklinikken
• Poland
  • Bydgoszcz, Poland, 85-667
    • Poradnia Chorob Metabolicznych
  • Warszawa, Poland, 04-730
    • Klinika Chorob Metabolicznych
• Puerto Rico
  • San German, Puerto Rico, 683
    • Hospital de la Concepcion
• Russian Federation
  • Moscow, Russian Federation, 119049
    • Moscow State Healthcare Institution 'Morozovskaya Children's City Clinical Hospital'
  • Saint-Petersburg, Russian Federation, 194100
    • Saint-Petersburg State Pediatric Medical Academy
  • Saint-Petersburg, Russian Federation, 196084
    • Saint-Petersburg State Healthcare Institution "Children's Polyclinic #35"
  • St Petersburg, Russian Federation, 194044
    • Autonomous Non-Profit Organization Medical Center 21 Century
• Slovakia
  • Bratislava, Slovakia, 833 40
    • Metabolicka ambulancia, 2. Detská klinika Lekárskej fakulty Univerzity Komenského
  • Kosice, Slovakia, 040 01
    • Detska fakultna nemocnica Kosice-old
  • Kosice, Slovakia, 040 11
    • Detska fakultna nemocnica Kosice
  • Poprad, Slovakia, 05801
    • Lipmet, s.r.o.
  • Trencin, Slovakia, 911 71
    • Fakultna nemocnica Trencin
• Spain
  • Barcelona, Spain, 08041
    • Hospital Santa Creu i Sant Pau
  • Esplugues de Llobregat, Spain, 08950
    • Hospital Sant Joan De Deu
  • Alicante
    • Elche, Alicante, Spain, 03202
      • Hospital General Universitario de Elche
  • Badajoz
    • Merida, Badajoz, Spain, 6800
      • Hospital de Mérida
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
• Switzerland
  • Ch-3010 Bern, Switzerland
    • Dr. med. Jean-Marc Nuoffer
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty. Department of Pediatrics. Nutrition and Metabolism Unit
  • Ankara, Turkey, 6500
    • Gazi University, Medical Faculty
  • Izmir, Turkey, 35100
    • Ege University Medical Faculty
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Medpace Clinical Pharmacology Unit
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin; All subjects will be treated with atorvastatin	Drug: atorvastatin; 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)

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Langslet G, Breazna A, Drogari E. A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2016 Sep-Oct;10(5):1153-1162.e3. doi: 10.1016/j.jacl.2016.05.010. Epub 2016 Jun 7.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: January 21, 2009
• First Submitted That Met QC Criteria: January 22, 2009
• First Posted (Estimate): January 23, 2009

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: pediatric heterozygous familial hypercholesterolemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: A2581173; 2008-006130-95 (EudraCT Number)