Pediatric Heterozygous Familial Hypercholesterolemia (heFH) MedDRA version: 8.0 Level: LLT Classification code 10057079
Conditions
Interventions
Trade Name: WelChol
Product Name: WelChol
Product Code: WelChol
Pharmaceutical Form: Tablet
INN or Proposed INN: colesevelam HCl
Other descriptive name: colesevelam HCl
Concentration unit: mg milligra
Sponsors
Sankyo Pharma Development (SPhD)
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 12-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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this trial is to evaluate the lipid lowering efficacy and safety of colesevelam HCl therapy administered to heFH 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 naïve to lipid-lowering therapy. For Period II (Day 1 to Week 8): To evaluate the low density lipoprotein cholesterol (LDL-C) lowering efficacy of colesevelam HCl administered to heFH patients on a stable dose of statins or who are treatment naïve to lipid lowering therapy.;Secondary Objective: For Period III (Week 8 to Week 26): To evaluate the long-term safety and efficacy of high dose colesevelam HCl administered to heFH patients while optimizing statin therapy for treatment to goal.;Primary end point(s): The primary endpoint for this trial in pediatric patients with heFH is that after 8 weeks of treatment (Period II), all patients receiving low dose (1875 mg) and high dose (3750 mg) colesevelam HCl will demonstrate superior lipid-lowering efficacy compared with patients treated with placebo as assessed by percent change from baseline in LDL-C reduction. | — |
Countries
Austria, Czech Republic, Hungary
Outcome results
None listed