Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity
Information source: University of Oslo School of Pharmacy
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Myotoxicity of Atorvastatin Treatment
Intervention: Atorvastatin (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: University of Oslo School of Pharmacy Official(s) and/or principal investigator(s):
Anders Åsberg, Ph.D., Study Director, Affiliation: Universtiy of Oslo
Overall contact:
Kjetil Retterstøl, MD, PhD, Phone: +4723070000, Email: kjetil.retterstol@rikshospitalet.no
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.
Clinical Details
Official title: Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity
Study design: Diagnostic, Non-Randomized, Single Blind (Investigator), Active Control, Single Group Assignment, Pharmacokinetics Study
Primary outcome: ratio of p-hydroxyatorvastatin to atorvastatin vs. myopathy
Secondary outcome: ratio of atorvastatin lactone to atorvastatin vs. myopathy
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(Unpublished data, Herman M et al).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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Suspected atorvastatin induced muscle adverse events.
- Signed informed consent.
- 18 years of age or older.
- Able to donate blood samples.
Locations and Contacts
Kjetil Retterstøl, MD, PhD, Phone: +4723070000, Email: kjetil.retterstol@rikshospitalet.no
Rikshospitalet-Radiumhospitalet HF, Lipid clinic, Oslo 0027, Norway; Recruiting
Kjetil Retterstøl, MD, Ph.D., Phone: +4723070000, Email: kjetil.retterstol@rikshospitalet.no
Additional Information
Starting date: May 2005
Ending date: March 2009
Last updated: February 12, 2009
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