Atorvastatin Three Year Pediatric Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00827606
First received: January 21, 2009
Last updated: June 1, 2015
Last verified: June 2015
  Purpose

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.


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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Low Density Lipoprotein Cholesterol (LDL-C; Millimoles Per Liter [mMol/L]) During the Study [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36 (or early termination [ET]) ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined.

  • Percent Change From Baseline in LDL-C [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36 (or ET) ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast).

  • High-Density Lipoprotein Cholesterol (HDL-C; mMol/L) During the Study [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined.

  • Percent Change From Baseline in HDL-C [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast).

  • Total Cholesterol (mMol/L) During the Study [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined.

  • Percent Change From Baseline in Total Cholesterol [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast).

  • Trigylcerides (mMol/L) During the Study [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined.

  • Percent Change From Baseline in Trigylcerides [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast).

  • Very Low-Density Lipoprotein (VLDL; mMol/L) During the Study [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined.

  • Percent Change From Baseline in VLDL [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast).

  • Apoliprotein A-1 (Apo A-1; Grams Per Liter [g/L]) During the Study [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined.

  • Percent Change From Baseline in Apo A-1 [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast).

  • Apoliprotein B (Apo B; g/L) During the Study [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast). Change from baseline was also determined.

  • Percent Change From Baseline in Apo B [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Assessments were performed in the fasting state (minimum 10-hour fast).

  • Number of Participants With Shift From Baseline in Tanner_Stage by Timepoint and Baseline Tanner_Stage [ Time Frame: Baseline, Months 6, 12, 18, 24, 30, and 36/ET ] [ Designated as safety issue: No ]
    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.

  • Height (Centimeters [cm]) During the Study: Males [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of height changes during the study. Change from baseline was also determined.

  • Percent Change From Baseline in Height: Males [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of height changes during the study.

  • Height (cm) During the Study: Females [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of height changes during the study. Change from baseline was also determined.

  • Percent Change From Baseline in Height: Females [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of height changes during the study.

  • Weight (Kilograms [kg]) During the Study: Males [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of weight changes during the study. Change from baseline was also determined.

  • Percent Change From Baseline in Weight: Males [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of weight changes during the study.

  • Weight (kg) During the Study: Females [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of weight changes during the study. Change from baseline was also determined.

  • Percent Change From Baseline in Weight: Females [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of weight changes during the study.

  • Body Mass Index (BMI in kg Per Square Meter [kg/m^2]) During the Study: Males [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of BMI changes during the study. Change from baseline was also determined.

  • Percent Change From Baseline in BMI: Males [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of BMI changes during the study.

  • BMI (kg/m^2) During the Study: Females [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of BMI changes during the study. Change from baseline was also determined.

  • Percent Change From Baseline in BMI: Females [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of BMI changes during the study.

  • Age (Years) During the Study: Males [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of age during the study. Change from baseline was also determined.

  • Percent Change From Baseline in Age: Males [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of age during the study.

  • Age (Years) During the Study: Females [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of age during the study. Change from baseline was also determined.

  • Percent Change From Baseline in Age: Females [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Investigator assessment of age during the study.

  • Flow-Mediated Dilatation (FMD) During the Study [ Time Frame: Baseline, Months 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Percent (%) FMD was calculated as (hyperemic diameter minus resting diameter) divided by the resting diameter multiplied by 100. Change from baseline was also determined.

  • Percent Change From Baseline in FMD [ Time Frame: Months 6, 12, 18, 24, 30 and 36/ET ] [ Designated as safety issue: No ]
    Percent (%) FMD was calculated as (hyperemic diameter minus resting diameter) divided by the resting diameter multiplied by 100.


Secondary Outcome Measures:
  • Percentage of Participants With Overall Expected Maturation and Development Consistent With Expectations as Assessed by the Investigator [ Time Frame: Baseline, Months 1, 2, 3, 6, 12, 18, 24, 30 and 36 (or early termination) ] [ Designated as safety issue: No ]
  • Percentage of Participants by Study Drug Compliance Category [ Time Frame: Months 1, 2, 3, 6, 12, 18, 24, 30, and 36 (or early termination) ] [ Designated as safety issue: No ]
    Compliance to study drug was categorized as <80%, 80% - 120%, and greater than (>) 120%.


Enrollment: 272
Study Start Date: March 2009
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   6 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  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: NCT00827606

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

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00827606     History of Changes
Other Study ID Numbers: A2581173, 2008-006130-95
Study First Received: January 21, 2009
Results First Received: September 11, 2014
Last Updated: June 1, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
pediatric heterozygous familial hypercholesterolemia

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
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015