Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity

University of Oslo School of Pharmacy

Status and phase: Completed; Phase 4

Conditions: Myotoxicity of Atorvastatin Treatment

Treatments: Drug: Atorvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT00414531

AVALIP05

Details and patient eligibility

About

The primary objective of the study is to investigate the ratios of p-hydroxyatorvastatin to atorvastatin in patients receiving atorvastatin treatment, who experience muscle adverse events, to elucidate whether differences in this ratio might have a positive or negative predictive value in diagnosing atorvastatin muscle toxicity.

Full description

The primary objective of the study is to investigate the ratios of p-hydroxyatorvastatin to atorvastatin in patients receiving atorvastatin treatment, who experience muscle adverse events, to elucidate whether differences in this ratio might have a positive or negative predictive value in diagnosing atorvastatin muscle toxicity. If this is shown, measurements of atorvastatin metabolites from patients experiencing muscle adverse events might be a valuable diagnostic tool to diagnose myopathy associated with statin treatment. The primary endpoint cut off level for present myotoxicity has been set to a ratio of p-hydroxyatorvastatin /atorvastatin of 0.15 from the previously performed pilot study (Unpublished data, Herman M et al). Values at or above this ratio will be considered as clinical significant indicia of statin related myopathy.

Secondary objectives include descriptively investigation of drug to metabolite cut off ratio for atorvastatin lactone/atorvastatin. Whether other cut off values, both for p-hydroxyatorvastatin as well as for atorvastatin lactone, give more precise identification of patients that are experiencing statin related myopathy compared to controls will also be investigated.

Explorative objectives of the study are to investigate possible in vitro phenotypic differences in isolated muscle cells from patients experiencing muscle toxicity compared to patients not experiencing muscle toxicity. If there are genetic differences between patients experiencing myotoxicity and those not, this difference is likely to show as phenotypic differences in in vitro studies of isolated muscle cells. If such phenotypic differences are present in vitro possible mechanistic causes will be further investigated.

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Suspected atorvastatin induced muscle adverse events.
• Signed informed consent.
• 18 years of age or older.
• Able to donate blood samples.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: Single Blind

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53 participants in 1 patient group

SIM

Other group

Description:

Patients diagnosed to have or not to have Statin induced Myopathy

Treatment:

Drug: Atorvastatin