HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA MedDRA version: 9.1 Level: LLT Classification code 10057079 Term: Heterozygous familial hypercholesterolemia
Conditions
Interventions
Product Name: Atorvastatin
Pharmaceutical Form: Tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Product Name: Atorvastatin
Pharmaceutical Form: Oral sol
Sponsors
Pfizer Inc,235 East 42nd Street,New York,NY 10017
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Male or female patients with genetically confirmed HeFH, aged between 6-17 years children and adolescents aged 10-17 years will also be at Tanner Stage II or higher in their development. Children aged 6-10 years will be at Tanner Stage I. 2. Genetically verified HeFH (i.e., FH confirmed by LDL receptor mutation analysis26 or by the lymphocyte test.27 If patients tested negative for the most common LDL receptor mutations, detection of FH would be carried out by assaying LDL receptors on lymphocytes). 3. LDL > 3mmol/L. 4. Parents/legal guardians must give written informed consent prior to the start of the study.Consent should be obtained from both (if available) of the child’s legal representatives (parents or guardians). Whenever the minor child is able to give assent, the minor’s assent must be obtained. 5. Subjects and parents/legal guardians must be thought to be compliant and able to follow the investigator’s instructions. They must be able to visit the clinic on schedule and be both cooperative and reliable. 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
Exclusion criteria: Subjects presenting with any of the following will not be included in the study: 1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (except FH), hepatic, psychiatric, neurologic, or allergic (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) disease or clinical findings at screening. 2. Weight 95th percentile for age. 3. Subject with any pathological conditions leading to precocious or delayed sexual development. 4. Pregnant or nursing females as well as females of childbearing potential who are unwilling or unable to use an acceptable method of nonhormonal contraception as outlined in this protocol from at least 14 days prior to the first dose of study medication through 28 days post last dose of study medication. 5. Active liver disease or hepatic dysfunction, AST or ALT =1.5 times the upper limit of normal range. 6. Subjects with a CPK >3 times the upper limit of the normal range. 7. Severe renal dysfunction, nephrotic syndrome, dysproteinemias, or TSH >10 mU/L. 8. Homozygous FH. 9. Treatment with an investigational drug within 4 weeks or 5 half-lives preceding the first dose of study medication. 10. Known hypersensitivities to HMG-CoA reductase inhibitors. 11. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Subjects will have no other concomitant medications including antihyperlipidemic therapy at study entry. Subjects previously receiving antihyperlipidemic therapy will be considered for screening after a minimum 4-week washout period before entering this study. If they were previously receiving the HMG-CoA, there will be a minimum 6 weeks washout period before entering this study. Subjects previously receiving the probucol need to have stopped the treatment for a minimum 6 months to be eligible to enter into this study. Herbal supplements and hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing IUDs, postcoital contraceptive methods) and hormone replacement therapy must be discontinued 28 days prior to the first dose of study medication. Depo-Provera® must be discontinued at least 6 months prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses Atorvastatin of =1 g/day. Limited use of non-prescription and prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor. 12. A positive urine drug screen. 13. Use of tobacco- or nicotine-containing products. 14. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening. 15. A 12-lead ECG at screening with significant abnormal finding. 16. Donation of blood in excess of 280 mL within 56 days prior to dosing. 17. Unwilling or unable to comply with the Lifestyle guidelines described in this protocol. 18. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product admini
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Population PK models for atorvastatin and its metabolites will be developed. Key parameters may include apparent clearance CL/F and/or apparent volume of distribution V/F of the plasma/central compartment. Key potential covariates include age and body weight. ;Main Objective: To develop population pharmacokinetic models for atorvastatin and its active metabolites (o-hydroxyatorvastatin and p-hydroxyatorvastatin) in children and adolescents with HeFH, and to examine the influence of covariates on the pharmacokinetic parameters.;Secondary Objective: To assess the pharmacodynamic responses of atorvastatin in children and adolescents with HeFH. To assess the safety and tolerability of atorvastatin in children and adolescents with HeFH. To explore possible relationship between exposure and pharmacodynamic responses. | — |
Countries
Netherlands
Outcome results
None listed