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

NCT00739999 | Completed Phase 1 Results

• 1 other identifier: A2581172
• Study Type: interventional
• Target: 39
• Locations: 3 countries
• Sites: 3

Brief Summary

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

Conditions

Pediatric Heterozygous Hypercholesterolemia

Keywords

heterozygous familial hypercholesterolemia (HeFH); atorvastatin; pediatric

Outcome Measures

Primary Outcomes (2)

• Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Atorvastatin Apparent Clearance (CL/F)

  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.

  Week 2, Week 4, Week 6, Week 8

• Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Apparent Volume of Distribution of the Central Compartment (Vc/F)

  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.

  Week 2, Week 4, Week 6, Week 8

Secondary Outcomes (16)

• Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)

  Baseline, Week 2, Week 4, Week 6, Week 8

• Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)

  Baseline, Week 2, Week 4, Week 6, Week 8

• Absolute Change From Baseline in Total Cholesterol (TC)

  Baseline, Week 2, Week 4, Week 6, Week 8

• Percent Change From Baseline in Total Cholesterol (TC)

  Baseline, Week 2, Week 4, Week 6, Week 8

• Absolute Change From Baseline in Triglycerides (TG)

  Baseline, Week 2, Week 4, Week 6, Week 8

Study Arms (2)

1

OTHER

6-10 years will be administered with atorvastatin tablet formulation with initial doses based on age cohort.

Drug: Atorvastatin

2

OTHER

10-17 years will be administered 10-mg daily dose of atorvastatin tablet formulation.

Drug: Atorvastatin

Interventions

Atorvastatin DRUG

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.

1

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Evidence or history of clinically significant diseases, homozygous familial hypercholesterolemia (FH)

Sponsors & Collaborators

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

Study Sites (3)

Pfizer Investigational Site

Québec, Quebec, G1V 4G2, Canada

Location

Pfizer Investigational Site

Athens, 115 27, Greece

Location

Pfizer Investigational Site

Oslo, 0027, Norway

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Atorvastatin

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.govCallCenter@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2008
• First Posted: August 22, 2008
• Study Start: December 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: March 15, 2021
• Results First Posted: August 20, 2010

Record last verified: 2021-02

Locations

GR (1); CA (1); NO (1)