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 Overview

• Status: Completed
• Conditions: Myotoxicity of Atorvastatin Treatment
• Intervention / Treatment: Drug: Atorvastatin

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has been set to a ratio of p-hydroxyatorvastatin /atorvastatin of 0.15 from the previously performed pilot study (Unpublished data, Herman M et al).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

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0027
    • Rikshospitalet-Radiumhospitalet HF, Lipid clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: SIM; Patients diagnosed to have or not to have Statin induced Myopathy	Drug: Atorvastatin; 20 to 80 mg per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ratio of p-hydroxyatorvastatin to atorvastatin vs. myopathy	march 2009

Secondary Outcome Measures

Outcome Measure	Time Frame
ratio of atorvastatin lactone to atorvastatin vs. myopathy	march 2009

Collaborators and Investigators

• Sponsor: University of Oslo School of Pharmacy
• Investigators: Study Director: Anders Åsberg, Ph.D., Universtiy of Oslo

Publications and helpful links

General Publications

• Skottheim IB, Bogsrud MP, Hermann M, Retterstol K, Asberg A. Atorvastatin metabolite measurements as a diagnostic tool for statin-induced myopathy. Mol Diagn Ther. 2011 Aug 1;15(4):221-7. doi: 10.1007/BF03256413.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (ACTUAL): June 1, 2009
• Study Completion (ACTUAL): June 1, 2009

Study Registration Dates

• First Submitted: December 20, 2006
• First Submitted That Met QC Criteria: December 20, 2006
• First Posted (ESTIMATE): December 21, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): December 3, 2014
• Last Update Submitted That Met QC Criteria: December 2, 2014
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Nervous System Diseases; Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Myotoxicity; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: AVALIP05