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

This study has been completed.
Sponsor:
Information provided by:
University of Oslo School of Pharmacy
ClinicalTrials.gov Identifier:
NCT00414531
First received: December 20, 2006
Last updated: August 11, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Myotoxicity of Atorvastatin Treatment
Drug: Atorvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Diagnostic
Official Title: Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity

Resource links provided by NLM:


Further study details as provided by University of Oslo School of Pharmacy:

Primary Outcome Measures:
  • ratio of p-hydroxyatorvastatin to atorvastatin vs. myopathy [ Time Frame: march 2009 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ratio of atorvastatin lactone to atorvastatin vs. myopathy [ Time Frame: march 2009 ] [ Designated as safety issue: No ]

Estimated Enrollment: 53
Study Start Date: May 2005
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Atorvastatin
    20 to 80 mg per day
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Suspected atorvastatin induced muscle adverse events.
  • Signed informed consent.
  • 18 years of age or older.
  • Able to donate blood samples.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00414531

Locations
Norway
Rikshospitalet-Radiumhospitalet HF, Lipid clinic
Oslo, Norway, 0027
Sponsors and Collaborators
University of Oslo School of Pharmacy
Investigators
Study Director: Anders Åsberg, Ph.D. Universtiy of Oslo
  More Information

No publications provided by University of Oslo School of Pharmacy

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Professor Anders Åsberg, School of Pharmacy, Univ. of Oslo
ClinicalTrials.gov Identifier: NCT00414531     History of Changes
Other Study ID Numbers: AVALIP05
Study First Received: December 20, 2006
Last Updated: August 11, 2009
Health Authority: Norway: Norwegian Medicines Agency

Additional relevant MeSH terms:
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014