A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication

NCT00655265 | Completed Phase 4

• 2 other identifiers: CHOL00107EudraCT 2007-000582-37
• Study Type: interventional
• Target: 86
• Locations: 5 countries
• Sites: 8

Brief Summary

This study is designed to assess whether colesevelam given as third line treatment added to a maximal tolerated and stable dose of a statin and ezetimibe is able to further decrease the level of LDL cholesterol in a safe and efficient manner in difficult to treat Familial Hypercholesterolaemia patients who are not at their target level of LDL cholesterol.

Conditions

Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Relative reduction in LDL cholesterol

  Between baseline and 6 weeks DB treatment

Secondary Outcomes (2)

• Relative reduction in HDL, total cholesterol, ApoA1,ApoB,ApoB/ApoA1ratio, triglycerides

  Between Baseline and week 6 and week 12 DB treatment

• Relative reduction in LDL cholesterol

  Between Baseline and week 12 DB treatment

Study Arms (2)

Colesevelam hydrochloride film-coated tablets

EXPERIMENTAL

Drug: Colesevelam hydrochloride film-coated tablets

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Colesevelam hydrochloride film-coated tablets DRUG

tablets

Also known as: Cholestagel

Colesevelam hydrochloride film-coated tablets

Placebo DRUG

Tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a clinical diagnosis of Familial Hypercholesterolaemia defined as EITHER a.Presence of a documented LDL-receptor mutation OR b. History of untreated LDL-cholesterol level above the 95th percentile for sex and age in combination with documentation of at least one of the following: i.Presence of typical tendon xanthomas in the patient or first degree relative. ii. An LDL-cholesterol level above the 95th percentile for age and sex in a first degree relative. iii. Proven coronary artery disease in the patient or in a first degree relative under the age of 60.
• Patients must have provided and undergone lifestyle changes for more than 6 months at the time of Screening
• Patients must have been treated for at least 3 consecutive months preceding the Screening visit with a lipid lowering treatment regimen consisting of maximal tolerated combination of a statin with ezetimibe and are still above their target for LDL cholesterol being 2.5 mmol/L (100 mg/dL)
• Patients must be committed to following the protocol requirements as evidence by written informed consent
• Patients should be comfortable with swallowing 3 placebo tablets

You may not qualify if:

• Patients with a known allergy to any of the components used in colesevelam or placebo or any other medications like statin or ezetimibe required for participation in this study
• Patients with a bowel or biliary obstruction
• Patients with secondary causes of hypercholesterolaemia, e.g., dysproteinaemia, hypothyroidism, nephrotic syndrome (defined as proteinuria \>2 g/L), obstructive liver disease, other pharmacological therapies, alcoholism
• Patients with triglyceride level of \> 3.4 mmol/L
• Patients with dysphagia, swallowing disorders, severe gastrointestinal motility disorders, inflammatory bowel disease, or major gastrointestinal tract surgery
• Patients have undergone LDL-apheresis within one year prior to the screening visit and/or need to undergo LDL-apheresis
• Patients with active liver disease or unexplained persistent elevations in transaminases
• Patients on fenofibrates or on concomitant cholestyramine as this will affect the area under the curve (AUC) of ezetimibe
• Patients with poorly-controlled diabetes (i.e., HbA1c\>9% at Screening)
• Patients with clinically significant (CS) abnormal haematology, renal, or other laboratory parameters that could be the result of an underlying malignancy or systemic infection as judged by the investigator
• Patients with a heart transplant, concurrent congestive heart failure (NYHA Class 3 or 4), life-threatening ventricular arrhythmias, unstable angina, recent myocardial infarction within the past 6 months prior to screening, or patients undergoing haemodialysis, or with active disease who may not be healthy enough to successfully complete all protocol requirements
• Fertile women who are pregnant, nursing or using either no or an inadequate form of contraception taking into account the recommendations for adequate intake of oral contraceptives as outlined in concomitant medication section
• Patients with a recent history of alcoholism or drug abuse, or sever emotional behavioural or psychiatric problems who may not be able to adequately comply with the requirements of the study or who may be unable to consent
• Patients receiving experimental medications or participating in another study using an experimental drug or procedure within 30 days prior to signing informed consent

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (8)

Service d'Endocrinologie, Metabolisme Prevention des Maladies Cardio-Vasculaires

Paris, France

Location

Kardiologie

Marburg, Germany

Location

Academic Medical Centre

Amsterdam, Netherlands

Location

University Medical Centre

Nijmegen, Netherlands

Location

University Medical Centre

Utrecht, Netherlands

Location

TweeSteden Ziekenhius

Waalwijk, Netherlands

Location

Centre for Metabolism and Endocrinology

Huddinge, Sweden

Location

Department of Medicine, University of Manchester

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Interventions

Colesevelam Hydrochloride

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Allylamine; Amines; Organic Chemicals; Allyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2008
• First Posted: April 9, 2008
• Study Start: August 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: October 1, 2009
• Last Updated: February 11, 2014

Record last verified: 2014-02

Locations

SE (1); NL (4); FR (1); GB (1); DE (1)