Official Title: “Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity”

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.

Study Type: Interventional

Study Design: Diagnostic, Non-Randomized, Single Blind (Investigator), Active Control, Single Group Assignment, Pharmacokinetics Study

Study Primary Completion Date: March 2009

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has been set to a ratio of p-hydroxyatorvastatin /atorvastatin of 0.15 from the previously performed pilot study (Unpublished data, Herman M et al).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

Intervention(s) in this Clinical Trial

• Drug: Atorvastatin
  • 20 to 80 mg per day

Primary Measures

• ratio of p-hydroxyatorvastatin to atorvastatin vs. myopathy
  • Time Frame: march 2009
    Safety Issue?: No

Secondary Measures

• ratio of atorvastatin lactone to atorvastatin vs. myopathy
  • Time Frame: march 2009
    Safety Issue?: No

Inclusion Criteria:

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Oslo School of Pharmacy

Overall Clinical Trial Officials and Contacts

Anders Åsberg, Ph.D. Study Director Universtiy of Oslo  

Overall Contact: Kjetil Retterstøl, MD, PhD +4723070000 kjetil.retterstol@rikshospitalet.no

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00414531

Study ID Number: AVALIP05

ClinicalTrials.gov Identifier: NCT00414531

Health Authority: Norway: Norwegian Medicines Agency