Efficacy and Safety of Colesevelam in Pediatric Patients With Genetic High Cholesterol

Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Colesevelam HCl Administered to Pediatric Patients With Heterozygous Familial Hypercholesterolemia on a Stable Dose of Statins or Treatment Naive to Lipid-lowering Therapy

This study will evaluate the lipid-lowering effect and safety of colesevelam therapy administered to heterozygous familial pediatric patients 10 through 17 years of age who are on a stable dose of a pediatric-approved statin monotherapy (atorvastatin, lovastatin, simvastatin or pravastatin), or who are treatment naive to lipid-lowering therapy.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: colesevelam HCl; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Camperdown NSW, Australia
• Austria
  • Vienna, Austria
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Ontario
    • Toronto, Ontario, Canada
  • Quebec
    • Chicoutimi, Quebec, Canada
    • Laval, Quebec, Canada
    • Stefoy, Quebec, Canada
• Israel
  • Holon, Israel
  • Jerusalem, Israel
  • Kefer Saba, Israel
  • Tel-Hashomer, Israel
• Netherlands
  • Amsterdam, Netherlands
  • Rotterdam, Netherlands
• Norway
  • Oslo, Norway
• South Africa
  • Observatory, South Africa
  • Pretoria, South Africa
  • Tygerberg, South Africa
• United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Missouri
    • St. Louis, Missouri, United States
  • New York
    • Bronx, New York, United States
    • New Hyde Park, New York, United States
    • New York, New York, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Pennsylvania
    • Wexford, Pennsylvania, United States
  • Utah
    • Salt Lake City, Utah, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients
• Ages 10 to 17 years inclusive
• Diagnosis of heterozygous familial hypercholesterolemia
• On a stable dose of statin monotherapy or are treatment naive to lipid- lowering agents
• On a low-cholesterol diet

Exclusion Criteria:

• Patients should not have serious concomitant conditions that could interfere with the analysis of the results or that could interfere with the well-being of the patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high dose colesevelam; colesevelam HCl 3.750 g	Drug: colesevelam HCl; Tablets
Experimental: Low dose colesevelam; Low dose colesevelam 1.875 g	Drug: colesevelam HCl; Tablets
Placebo Comparator: placebo; placebo comparator	Drug: placebo; Matching Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Plasma Low Density Lipoprotein-cholesterol (LDL-C) From Day 1 (Study Baseline) to Week 8.	Percent change in LDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline)to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.	8 weeks (week 8 - day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Plasma Total Cholesterol (TC) From Day 1 (Study Baseline) to Week 8.	Percent change in total cholesterol (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.	8 weeks (week 8 - day 1)
Percent Change in Plasma Triglycerides (TG) From Day 1 (Study Baseline) to Week 8.	Percent change in triglycerides (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.	8 weeks (week 8 - day 1)
Percent Change in Plasma High-density Lipoprotein-cholesterol (HDL-C) From Day 1 (Study Baseline) to Week 8.	Percent change in HDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.	8 weeks (week 8 - day 1)
Percent Change in Plasma Non-high Density Lipoprotein-cholesterol (Non-HDL-C) From Day 1 (Study Baseline) to Week 8.	Percent change in non-HDL-C (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.	8 weeks (week 8 - day 1)
Percent Change in Plasma Apolipoprotien A-I (Apo A-1) From Day 1 (Study Baseline) to Week 8.	Percent change in Apolipoprotien A-I (Apo A-1) (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.	8 weeks (week 8 - day 1)
Percent Change in Plasma Apolipoprotein B (Apo B) From Day 1 (Study Baseline) to Week 8.	Percent change in Apo B (mg/dL) and standard deviation (SD) from Day 1 (Study Baseline) to Week 8 (last observation carried forward - LOCF)- Intent-to-Treat ITT population.	8 weeks (week 8 - day 1)
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Study Baseline (Day 1) to Week 26.	Percent change in low-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.	26 weeks (week 26 - day 1)
Percent Change in Total Cholesterol From Study Baseline (Day 1) to Week 26.	Percent change in total cholesterol (TC) from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.	26 weeks (week 26 - day 1)
Percent Change in Triglycerides From Study Baseline (Day 1) to Week 26.	Percent change in triglycerides from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.	26 weeks (week 26 - day 1)
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Study Baseline (Day 1) to Week 26.	Percent change in high-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.	26 weeks (week 26 - day 1)
Percent Change in Non-high-density Lipoprotein Cholesterol From Study Baseline (Day 1) to Week 26.	Percent change in non-high-density lipoprotein cholesterol from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.	26 weeks (week 26 - day 1)
Percent Change in Apolipoprotein A-I From Study Baseline (Day 1) to Week 26.	Percent change in apolipoprotein A-I from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.	26 weeks (week 26 - day 1)
Percent Change in Apolipoprotein B From Study Baseline (Day 1) to Week 26.	Percent change in apolipoprotein B from baseline to Week 26 was calculated for subpopulations representing each assigned treatment group during the Double blind Period, and for the overall population in the Open Label Extension Period.	26 weeks (week 26 - day 1)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• Stein EA, Marais AD, Szamosi T, Raal FJ, Schurr D, Urbina EM, Hopkins PN, Karki S, Xu J, Misir S, Melino M. Colesevelam hydrochloride: efficacy and safety in pediatric subjects with heterozygous familial hypercholesterolemia. J Pediatr. 2010 Feb;156(2):231-6.e1-3. doi: 10.1016/j.jpeds.2009.08.037. Epub 2009 Oct 31.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: September 1, 2005
• First Submitted That Met QC Criteria: September 1, 2005
• First Posted (Estimate): September 5, 2005

Study Record Updates

• Last Update Posted (Estimate): April 15, 2010
• Last Update Submitted That Met QC Criteria: April 8, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: Pediatric; hypercholesterolemia; colesevelam
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride
• Other Study ID Numbers: WEL-410