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 Naïve to Lipid-Lowering Therapy

• Conditions: MedDRA version: 8.1Level: LLTClassification code 10057079Term: Heterozygous familial hypercholesterolemia; Pediatric Heterozygous Familial Hypercholesterolemia (heFH)

• Registration Number: EUCTR2005-003511-75-CZ
• Lead Sponsor: Daiichi Sankyo Pharma Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-11
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Written informed consent from the patient’s parent or guardian and assent from the patient. (Consent form is approved by the institutional review board (IRB) or other committee).

2. Male or female patient is 10 through 17 years of age.

3. Patient has a diagnosis of heFH defined as a known mutation in a copy of the patient’s LDL-receptor or apolipoprotein B (Apo B) gene. In the absence of a genetic diagnosis the patient must have the following LDL-C criteria to be classified as a heFH patient:
• A documented history of untreated LDL-C >160 mg/dL (4.14 mmol/L) In combination with at least one of the following:
• The history or presence, in the patient or a first degree relative, of a documented tendinous or cutaneous xanthoma or premature (before age 45 years) corneal arcus; or
• The history or presence, in an adult first-degree relative or biological offspring of a documented mutation in a copy of the individual’s (relative or offspring) LDL-receptor or apolipoprotein B (Apo B) gene; or
• The presence, in an adult first-degree relative, of documented untreated LDL-C >190 mg/dL (4.9 mmol/L), or sibling <18 years old with LDL-C >160 mg/dL (4.14 mmol/L); or
• A documented history, in a first-degree relative, of premature coronary artery disease or sudden death from natural causes prior to age 55 years if male, or prior to age 60 years of age if female.

4. Patient has LDL-C >130 mg/dL (3.37 mmol/L) while on statin therapy, or LDL-C >160 mg/dL (4.14 mmol/L) naïve to hypolipidemic therapy and diet stabilized.

5. Patient must be stable on a statin plus diet for 6-weeks; or for lipid-lowering treatment naïve patient, stable on a NCEP Step 1 diet or equivalent for 4 weeks prior to Visit 1.

6. Triglycerides (TG) at Visit 1 <250 mg/dL (2.83 mmol/L).

7. Patients should be of at least Tanner Stage 2.

8. Female patients may enroll if all 5 of the following criteria are met:
• At least 1 year post-menarche
• Negative urine pregnancy test at screening
• Not lactating
• Do not plan to become pregnant during the study
• Use appropriate contraceptive methods if sexually active. If the patient is on oral contraceptives, it needs to be taken at least 3 months prior to randomization.

9. Mean treatment compliance during Period I (Visit 2 and Visit 3) must be =75%.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patients unable or unwilling to take the study drug.

2. Secondary hyperlipidemia (e.g., due to biliary cirrhosis, dietary abnormalities, nephrotic syndrome, hypothyroidism, etc.).

3. Fasting TG =250 mg/dL (2.83 mmol/L).

4. Homozygous familial hypercholesterolemia.

5. Patients with a history of dysphagia, swallowing disorders, intestinal motility disorders.

6. Hypertension due to renal disease.

7. Untreated thyroid disease.

8. Clinically important liver or renal disorder, or vasculitis. Patients with mild to moderate liver steatosis, per investigator assessment, may be included.

9. Poorly controlled Type 1 or Type 2 diabetes mellitus defined as HbA1c >9.0%. Diabetics must have documentation of HbA1c within 3 months of the screening visit. Undocumented patients must have their HbA1c assessed at Visit 1. Note: Patients with Type 1/Type 2 diabetes controlled with insulin and/or oral hypoglycemic agents on a stable dose for last 30 days prior to Visit 1 may be included.

10. Patients who require or are taking any concomitant medication, which may interfere with the objectives of the study. Use of oral anticoagulants or digoxin, unless the dose has been stable for 4 weeks prior to Visit 1 and regular clinical laboratory monitoring is performed.

11. Screening laboratory values within the following age/gender appropriate reference ranges as assessed by the central laboratory:
• Hemoglobin
Male <10 g/dL
Female <9 g/dL
• Alanine Transaminase (ALT) (SGPT) >2 x Upper Limit Normal(ULN) for age
• Aspartate Transaminase (AST) (SGOT) >2 x ULN for age
• Alkaline Phosphatase >2 x ULN for age
• Total bilirubin >1 x ULN (unless elevations due to congenital bilirubin metabolism defect, i.e. Gilbert Syndrome)
• Creatine Phosphokinase (CPK) >5 x ULN for gender unless explained by exercise

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified