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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00655265
First received: April 3, 2008
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Familial Hypercholesterolemia
Drug: Colesevelam hydrochloride film-coated tablets
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 4 Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, MultiCentre Study of Colesevelam as Add-on Therapy in Patients With Familial Hypercholesterolaemia

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Relative reduction in LDL cholesterol [ Time Frame: Between baseline and 6 weeks DB treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relative reduction in HDL, total cholesterol, ApoA1,ApoB,ApoB/ApoA1ratio, triglycerides [ Time Frame: Between Baseline and week 6 and week 12 DB treatment ] [ Designated as safety issue: No ]
  • Relative reduction in LDL cholesterol [ Time Frame: Between Baseline and week 12 DB treatment ] [ Designated as safety issue: No ]

Enrollment: 86
Study Start Date: August 2007
Study Completion Date: October 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Colesevelam hydrochloride film-coated tablets Drug: Colesevelam hydrochloride film-coated tablets
tablets
Other Name: Cholestagel
Placebo Comparator: Placebo Drug: Placebo
Tablets

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  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: NCT00655265

Locations
France
Service d'Endocrinologie, Metabolisme Prevention des Maladies Cardio-Vasculaires
Paris Cedex, France
Germany
Kardiologie
Marburg, Germany
Netherlands
Academic Medical Centre
Amsterdam, Netherlands
University Medical Centre
Nijmegen, Netherlands
University Medical Centre
Utrecht, Netherlands
TweeSteden Ziekenhius
Waalwijk, Netherlands
Sweden
Centre for Metabolism and Endocrinology
Huddinge, Sweden
United Kingdom
Department of Medicine, University of Manchester
Manchester, United Kingdom
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00655265     History of Changes
Other Study ID Numbers: CHOL00107, EudraCT 2007-000582-37
Study First Received: April 3, 2008
Last Updated: February 10, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Sweden: Medical Products Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Colesevelam
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014