Pharmacokinetics of Rosuvastatin and Atorvastatin in Pediatric Dyslipidemia Patients

• Status: Completed
• Trial end date: 2017-12-27
• Target enrollment: 0
• Participant gender: All

Summary

This will be a single center, open label, randomized, cross-over study in patients with dyslipidemia comparing the pharmacokinetics of rosuvastatin and atorvastatin in patients with greater than or equal to one variant allele in the SLCO1B1 gene (-11187 and/or c.521) to patients with the wild-type/wild-type genotype.

The studies goal is to establish the role of genetic variation and development in key transporters on the dose-exposure relationship of two commonly used statin drugs in children. This study is the first step in a series of investigations aimed to determining the mechanisms behind variations in physiologic response, clinical efficacy and significant adverse effect risk that surround the statin drugs in children and adolescents.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Children's Mercy Hospital Kansas City
• Treatments: Atorvastatin; Atorvastatin Calcium; Rosuvastatin Calcium

Criteria

Inclusion Criteria:

1. Children 8-21 years of age

2. LDL cholesterol >130mg/dl (>95% percentile)

3. Successfully genotyped for SLCO1B1

4. Willing to sign the assent/permission/consent form

Exclusion Criteria:

1. Underlying structural heart disease including congenital heart disease or acquired heart disease.

2. History or laboratory evidence of an underlying intestinal, metabolic, autoimmune, or renal disease that could alter the disposition of rosuvastatin or atorvastatin.

3. Underlying pathology of the gastrointestinal tract or recent surgery which would be expected to alter the rate and/or extent of drug absorption

4. Evidence of previous hypersensitivity to statin medications

5. Unwillingness or inability to have screening labs drawn

6. Refusal to participate in the study

7. Unwillingness or inability to participate in an overnight fast

8. Subjects taking drugs with interactions with statins (CYP3A4 inducers/inhibitors, OATP1B1 inducers/inhibitors) (Appendix 1)

9. Inability to swallow a tablet drug

10. For females, a positive urine beta-human chorionic gonadotropin pregnancy test result

11. Evidence of hepatic abnormality as determined by values > 3 times the age-specific upper limit of normal for AST, ALT, total and conjugated bilirubin, serum albumin, Alkaline Phosphatase, and GGT.

12. Abnormal red blood cell morphology and/or a hemoglobin less than 9 gm/dl

13. Diarrhea in the last 24 hours