8-Week PK/PD Atorvastatin Study In Children And Adolescents With Heterozygous Familial Hypercholesterolemia

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00739999
First received: August 21, 2008
Last updated: August 19, 2010
Last verified: June 2009

August 21, 2008
August 19, 2010
December 2008
May 2009   (final data collection date for primary outcome measure)
  • Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Atorvastatin Apparent Clearance (CL/F) [ Time Frame: Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Parent-metabolite population PK model built using sparse blood samples from both Tanner Stage 1 and Tanner Stage 2+. Blood sampling times: Weeks 2 and 6: single sample between 4 and 12 hours postdose; Weeks 4 and 8: predose, 1 hour, and 2 hours postdose. Plasma samples were analyzed for atorvastatin and active hydroxyacid metabolite (o-hydroxyatorvastatin) concentrations using a validated, sensitive, and specific high-performance liquid chromatography tandem mass spectrometric method. Data presented are the result of the model used.
  • Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Apparent Volume of Distribution of the Central Compartment (Vc/F) [ Time Frame: Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Parent-metabolite population PK model built using sparse blood samples from Tanner Stages 1 and 2+. Sampling times: Weeks 2 + 6: single sample between 4 -12 hours postdose; Weeks 4 + 8: predose, 1 + 2 hours postdose. Plasma samples analyzed for atorvastatin and active hydroxyacid metabolite (o-hydroxyatorvastatin) concentrations using validated, sensitive, specific high-performance liquid chromatography tandem mass spectrometric method. Vc/F value based on 70 kg body weight. Parameter estimation uncertainty (95% CI) by non-parametric bootstrap analysis. Data presented are result of model used.
• Population PK models for atorvastatin and its metabolites will be developed. Key parameters may include apparent clearance CL/F and/or apparent volume of distribution V/F of the plasma/central compartment [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00739999 on ClinicalTrials.gov Archive Site
  • Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Low-density lipoprotein cholesterol (LDL-C) measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value.
  • Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Low-density Lipoprotein Cholesterol (LDL-C): percent (%) change from baseline by treatment over time = [LDL-C at observation minus LDL-C at Week 0] divided by LDL-C at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]).
  • Absolute Change From Baseline in Total Cholesterol (TC) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Total Cholesterol measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value.
  • Percent Change From Baseline in Total Cholesterol (TC) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Total cholesterol (TC): percent (%) change from baseline by treatment over time = [TC at observation minus TC at Week 0] divided by TC at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]).
  • Absolute Change From Baseline in Triglycerides (TG) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Change from baseline in triglycerides measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value.
  • Percent Change From Baseline in Triglycerides (TG) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Triglycerides (TG): percent (%) change from baseline by treatment over time = [TG at observation minus TG at Week 0] divided by TG at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]).
  • Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Change from baseline in high-density lipoprotein cholesterol measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value.
  • Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    High-density lipoprotein cholesterol (HDL-C): percent (%) change by treatment over time = [HDL-C at observation minus HDL-C at Week 0] divided by HDL-C at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]).
  • Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Change from baseline in Apolipoprotein A-1 measured in grams per liter (g/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value.
  • Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Apolipoprotein A-1 (Apo A-1): percent (%) change from baseline by treatment over time = [Apo A-1 at observation minus Apo A-1 at Week 0] divided by Apo A-1 at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]).
  • Absolute Change From Baseline in Apolipoprotein B (Apo B) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Change from baseline in Apolipoprotein B measured in grams per liter (g/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value.
  • Percent Change From Baseline in Apolipoprotein B (Apo B) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Apolipoprotein B (Apo B): percent (%) change from baseline by treatment over time = [Apo B at observation minus Apo B at Week 0] divided by Apo B at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]).
  • Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Change from baseline in very low-density lipoprotein-cholesterol (VLDL-C) measured in millimoles per liter (mmol/L). Change from baseline = value at observation minus baseline value. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]).
  • Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ] [ Designated as safety issue: No ]
    Very low-density lipoprotein-cholesterol (VLDL-C): percent (%) change from baseline by treatment over time = [VLDL-C at observation minus VLDL-C at Week 0] divided by VLDL-C at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]).
  • Absolute Change From Baseline in Flow-Mediated Dilatation at Week 8 [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    Brachial artery flow-mediated dilatation (FMD) = (max minus baseline diameter divided by baseline diameter) x 100%. Standardized image acquisition: brachial artery images recorded for one minute at rest, blood pressure cuff inflated to 250 mm Hg for 5 minutes with brachial artery imaged continuously throughout cuff inflation, cuff released to produce reactive hyperaemia and the brachial artery imaged continuously for 3 minutes after release. Total duration of measurement approximately 25 minutes. Change from baseline = value at observation minus baseline value.
  • Percent Change From Baseline in Flow-Mediated Dilatation at Week 8 [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]

    Brachial Flow-Mediated Dilatation (FMD) = (max minus baseline diameter divided by baseline diameter) x 100%.

    .

  • Change and % change from baseline in pharmacodynamic responses of LDL, TC, TG, HDL, VLDL, and Apo A-1, and Apo B [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Safety laboratory tests, vital signs, and adverse events [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
8-Week PK/PD Atorvastatin Study In Children And Adolescents With Heterozygous Familial Hypercholesterolemia
A 8-Week, Open-Label, Phase 1 Study To Evaluate Pharmacokinetics, Pharmacodynamics, Safety And Tolerability Of Atorvastatin In Children And Adolescents With Heterozygous Familial Hypercholesterolemia

To evaluate pharmacokinetics, pharmacodynamics, safety and tolerability of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia

Not Provided
Interventional
Phase 1
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Pediatric Heterozygous Hypercholesterolemia
  • Drug: Atorvastatin
    6-10 years Tanner Stage 1 will be administered 5-mg daily dose of an atorvastatin pediatric tablet formulation. Dose may be doubled if subjects have not attained target LDL (<3.35 mmol/L) after 4-week treatment.
  • Drug: Atorvastatin
    10-17 years Tanner Stage 2 will be administered 10-mg daily dose of atorvastatin tablet formulation. Dose may be doubled if subjects have not attained target LDL (<3.35 mmol/L) after 4-week treatment.
  • 1
    6-10 years will be administered with atorvastatin tablet formulation with initial doses based on age cohort.
    Intervention: Drug: Atorvastatin
  • 2
    10-17 years will be administered 10-mg daily dose of atorvastatin tablet formulation.
    Intervention: Drug: Atorvastatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
39
May 2009
May 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Genetically confirmed heterozygous familial hypercholesterolemia (HeFH) with LDL greater or equal 4 mmol/L at baseline

Exclusion Criteria:

  • Evidence or history of clinically significant diseases, homozygous familial hypercholesterolemia (FH)
Both
6 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada,   Greece,   Norway
 
NCT00739999
A2581172
No
Director, Clinical Trial Disclosure Group, Pfizer, Inc.
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
June 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP