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

Myotoxicity of Atorvastatin Treatment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00414531
• Other study ID #: AVALIP05
• Status: Completed
• Phase: Phase 4
• First received: December 20, 2006
• Last updated: December 2, 2014
• Start date: May 2005
• Est. completion date: June 2009

Study information

• Verified date: August 2009
• Source: University of Oslo School of Pharmacy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

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has been set to a ratio of p-hydroxyatorvastatin /atorvastatin of 0.15 from the previously performed pilot study (Unpublished data, Herman M et al).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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Suspected atorvastatin induced muscle adverse events.

• Signed informed consent.

• 18 years of age or older.

• Able to donate blood samples.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Investigator), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Myotoxicity of Atorvastatin Treatment

Intervention

Drug:
• Atorvastatin
20 to 80 mg per day

Locations

Country	Name	City	State
Norway	Rikshospitalet-Radiumhospitalet HF, Lipid clinic	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
University of Oslo School of Pharmacy

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ratio of p-hydroxyatorvastatin to atorvastatin vs. myopathy		march 2009	No
Secondary	ratio of atorvastatin lactone to atorvastatin vs. myopathy		march 2009	No