Pharmacokinetics of Rosuvastatin and Atorvastatin in Pediatric Dyslipidemia Patients

NCT02364258 | Completed Phase 1

• 1 other identifier: 13020063
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dyslipidemia

Outcome Measures

Primary Outcomes (4)

• Evaluate effect of genotype (SLCO1BI) on Cmax rosuvastatin

  2 years

• Evaluate effect of genotype (SLCO1B1) on AUC rosuvastatin

  2 years

• Evaluate effect of genotype (SLCO1BI) on Cmax atorvastatin

  2 years

• Evaluate effect of genotype (SLCO1B1) on AUC atorvastatin

  2 years

Secondary Outcomes (21)

• Evaluate the effect of age on Cmax of rosuvastatin

  2 years

• Evaluate the effect of gender on Cmax of rosuvastatin

  2 years

• Evaluate the effect of race on Cmax of rosuvastatin

  2 years

• Evaluate the effect of sexual maturity on Cmax of rosuvastatin

  2 years

• Evaluate the effect of age on Cmax of atorvastatin

  2 years

Study Arms (2)

Rosuvastatin

EXPERIMENTAL

Rosuvastatin 10mg tablet (ages 8-21 years); 1 time dose given per oral at the start of the study day.

Drug: Rosuvastatin

Atorvastatin

EXPERIMENTAL

Atorvastatin 10mg tablet (ages 8-21 years); 1 time dose given per oral at the start of the study day.

Drug: Atorvastatin

Interventions

Rosuvastatin DRUG

Rosuvastatin 10mg tablet (ages 8-21 years); 1 time dose given per oral at the start of the study day.

Also known as: Crestor

Rosuvastatin

Atorvastatin DRUG

Atorvastatin 10mg tablet (ages 8-21 years); 1 time dose given per oral at the start of the study day.

Also known as: Lipitor

Atorvastatin

Eligibility Criteria

• Age: 8 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children 8-21 years of age
• LDL cholesterol \>130mg/dl (\>95% percentile)
• Successfully genotyped for SLCO1B1
• Willing to sign the assent/permission/consent form

You may not qualify if:

• Underlying structural heart disease including congenital heart disease or acquired heart disease.
• History or laboratory evidence of an underlying intestinal, metabolic, autoimmune, or renal disease that could alter the disposition of rosuvastatin or atorvastatin.
• Underlying pathology of the gastrointestinal tract or recent surgery which would be expected to alter the rate and/or extent of drug absorption
• Evidence of previous hypersensitivity to statin medications
• Unwillingness or inability to have screening labs drawn
• Refusal to participate in the study
• Unwillingness or inability to participate in an overnight fast
• Subjects taking drugs with interactions with statins (CYP3A4 inducers/inhibitors, OATP1B1 inducers/inhibitors) (Appendix 1)
• Inability to swallow a tablet drug
• For females, a positive urine beta-human chorionic gonadotropin pregnancy test result
• 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.
• Abnormal red blood cell morphology and/or a hemoglobin less than 9 gm/dl
• Diarrhea in the last 24 hours

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead

Study Sites (1)

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

MeSH Terms

Conditions

Dyslipidemias

Interventions

Rosuvastatin Calcium; Atorvastatin

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Jon B Wagner, DO

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Cardiologist/Clinical Pharmacology, Children's Mercy Hospital and Clinics

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 18, 2015
• Study Start: July 1, 2014
• Primary Completion: December 27, 2017
• Study Completion: December 27, 2017
• Last Updated: January 31, 2019

Record last verified: 2019-01

Locations

US (1)