Lipid-lowering Therapy Individualization

Hypercholesterolemia Clinical Trial

Official title:

Lipid-lowering Therapy Individualization

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03604471
• Other study ID #: 2016/26OCT/471
• Status: Completed
• Phase: Phase 4
• Start date: August 8, 2017
• Est. completion date: August 27, 2019

Study information

• Verified date: August 2019
• Source: Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical study will explore individual factors influencing statin pharmacokinetics in a cohort of 150 patients treated with atorvastatin.

Description:

Atorvastatin is widely prescribed for the treatment of hypercholesterolemia to prevent the risk of cardiovascular diseases, a leading death cause in industrialized countries. There exists considerable inter-individual variability in response to statins, reflected by differences in lipid-lowering effect or risk of presenting adverse drug reaction; mainly myotoxicity. A plethora of different factors (demographic, genetic, physiopathologic, environmental...) have been tested to explain this variability but it lacks of pharmacokinetic (PK) data and/or replications of observations are rare and results remain inconclusive, probably because of non-adapted designs and no-clear driven-hypothesis but also due to a lack of scientific rationale and deep mechanistic understanding. This clinical study will explore individual factors influencing statin PK in a cohort of 150 patients treated with atorvastatin. The collection of meticulous clinical PK data and a rigorous statistical analysis will allow quantifying the effect of each identified parameter on statin PK and eventually, defining a population-based PK model taking into account the combined effect of all covariates in a quantitative approach. This innovative prospectively designed clinical study will ultimately allow predicting atorvastatin PK fluctuations and anticipating any inadequate dosing in clinical care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: August 27, 2019
• Est. primary completion date: August 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Treatment with atorvastatin (any dose)

Exclusion Criteria:

• Unable to provide informed consent

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Atorvastatin
Blood sampling for atorvastatin quantification and pharmacogenetic analysis.

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc	Brussels

Sponsors (2)

Lead Sponsor	Collaborator
Université Catholique de Louvain	Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Atorvastatin population pharmacokinetics	Concentrations of atorvastatin acid (pmol/ml) will be measured by HPLC-MS using sparse samples obtained over the entire study period. Data will be pooled and analyzed using population pharmacokinetic modeling. The reported pharmacokinetic parameters will depend on the type of model that best fits the data.	18 months
Primary	Atorvastatin metabolites population pharmacokinetics	Concentrations of ortho-hydroxyatorvastatin (pmol/ml), para-hydroxyatorvastatin (pmol/ml) and atorvastatin lactone (pmol/ml) will be measured by HPLC-MS using sparse samples obtained over the entire study period. Data will be pooled and analyzed using population pharmacokinetic modeling. The reported pharmacokinetic parameters will depend on the type of model that best fits the data.	18 months
Secondary	Cholesterol	Measurement of total cholesterol, LDL cholesterol and HDL cholesterol at each visit	18 months
Secondary	Creatine kinase	Measurement of creatine kinase at each visit	18 months
Secondary	Occurrence of adverse drug events	Reports of adverse drug events will be recorded at each visit using a standardized questionnaire that includes the following categories : muscle cramps (grade 1 to 5), muscle pain (graded 1 to 5), rhabdomyolysis, gastro-intestinal side effects (Nauseas, diarrhea or vomitus), other side effects.	18 months
Secondary	Pharmacogene genotype	Patients will be genotyped for single nucleotide polymorphisms of interest in the following genes : ABCB1, ABCC1, ABCC2, ABCC4, ABCC5, ABCG2, CYP3A4, CYP3A5, NR1I2, POR, PPARalpha, SLCO1B1, SLCO2B1, SLCO3A1.	18 months
Secondary	Triglycerides	Measurement of triglyceride levels at each visit	18 months