Elevated LDL cholesterol level familial hypercholesterolaemia
Conditions
Interventions
One group will receive 6 tablets/day Colesevelam and one group will receive 6
tablets/day Placebo for a period of 12 weeks. This procedure is dubbel blind
Sponsors
Genzyme
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients must be males or females between 18 and 75 years of age, inclusive 2. Patients must have a clinical diagnosis of Familial Hypercholesterolaemia (FH) 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 3. Patients must have been provided and undergone lifestyle changes for more than 6 months at time of Screening 4. Patients must have been treated for at least 3 consecutive months preceding the screening visit with a stable lipid lowering treatment regimen consisting of a 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) 5. Patients must be committed to following the protocol requirements as evidenced by written informed consent 6. Patients should be comfortable with swallowing at least 3 placebo tablets
Exclusion criteria
Exclusion criteria: 1. 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 2. Patients with a bowel or biliary obstruction 3. Patients with secondary causes of hypercholesterolaemia, e.g., hypothyroidism, nephrotic syndrome (defined as proteinuria >2 g/L), dysproteinaemias, obstructive liver disease, other pharmacological therapies, alcoholism 4. Patients with triglyceride level of > 3.4 mmol/L. 5. Patients with dysphagia, swallowing disorders, severe gastrointestinal motility disorders, inflammatory bowel disease, or major gastrointestinal tract surgery 6. Patients having undergone LDL-apheresis within one year prior to the screening visit and/or need to undergo LDL-apheresis 7. Patients with active liver disease or unexplained persistent elevations in transaminases 8. Patients on fenofibrates or on concomitant cholestyramine as this will affect the area under the curve (AUC) of ezetimibe 9. Patients with poorly-controlled diabetes (i.e., glycosylated haemoglobin (HbA1c) > 9% at Screening) 10. 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 11. Patients with a heart transplant, concurrent congestive heart failure (New York Heart Association [NYHA] Class 3 or 4), life threatening ventricular arrhythmias, unstable angina, recent myocardial infarction within the past 6 month prior to screening or patients undergoing haemodialysis, or with active disease who may not be healthy enough to successfully complete all protocol requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint is the relative reduction in LDL cholesterol at Week 6 compared to Baseline and the difference between colesevelam and placebo. Baseline is defined as the LDL cholesterol level taken the closest in time to the Day 1 visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints will be the relative reduction in HDL cholesterol, total cholesterol, ApoA1, ApoB, ApoB/ApoA1 ratio, and triglycerides between Baseline and Week 6 and Week 12 and the differences between colesevelam and placebo; changes in fasting glucose, HbA1c level and hsCRP at Week 6 and Week 12; the percentage of patients being below their target for LDL cholesterol of 2.5 mmol/L (100 mg/dL) at Week 6 and Week 12 (goal rate); the percentage of patients with a relative reduction in their LDL cholesterol at Week 6 or Week 12 compared to Baseline of at least 15% or more (responder rate); and the relative reduction of LDL cholesterol at 12 weeks compared to Baseline and the difference between colesevelam and placebo. | — |
Countries
Netherlands
Outcome results
None listed