Safety and Efficacy of Idebenone versus Tacrine in Patients with Alzheimer's Disease: Results of a Randomized, Double-Blind, Parallel-Group Multicenter Study

H. Gutzmann; K.-P. Kühl; D. Hadler; M. A. Rapp

doi:10.1055/s-2002-19833

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2002; 35(1): 12-18
DOI: 10.1055/s-2002-19833

Original Paper

Safety and Efficacy of Idebenone versus Tacrine
in Patients with Alzheimer's Disease:
Results of a Randomized, Double-Blind, Parallel-Group Multicenter Study

H. Gutzmann¹ , K.-P. Kühl² , D. Hadler³ , M. A. Rapp^1, ⁴

¹Wilhelm Griesinger Hospital, Department of Gerontopsychiatry, Berlin, Germany
²Freie Universität Berlin, Department of Gerontopsychiatry, Berlin, Germany
³Takeda Europe R & D Center, Frankfurt/Main, Germany
⁴Now at the Max Planck Institute for Human Development, Berlin, Germany

The authors wish to dedicate this article to Professor Dr. S. Kanowski, Head of the Department of Gerontopsychiatry, Freie Universität of Berlin, on the occasion of his 65th birthday on February 23, 2000. Funding This study was in part supported by an educational grant from Takeda Europe to PD Dr. H. Gutzmann.

Abstract

This study evaluated the safety and efficacy of idebenone vs. tacrine in a prospective, randomized, double-blind, parallel-group multicenter study in patients suffering from dementia of the Alzheimer type (DAT) of mild to moderate degree. Diagnosis was based on DSM-III-R (primary degenerative dementia) and NINCDS-ADRDA criteria (probable Alzheimer's disease). A total of 203 patients of both sexes aged between 40 and 90 years were randomized to either idebenone 360 mg/day (n = 104) or tacrine up to 160 mg/day (n = 99) and treated for 60 weeks. The primary outcome measure was the Efficacy Index Score (EIS). The EIS combines dropout as well as the relevant improvements individually across the three levels of assessment (cognitive function, activities of daily living, global function). Secondary outcome measures were the ADAS-Cog score, the NOSGER-IADL score and the clinical global response (CGI-Improvement). After 60 weeks of treatment, 28.8 % of the patients randomized to idebenone, but only 9.1 % of the patients randomized to tacrine were still on the drug. In the LOCF analysis, 50 % of the patients randomized to idebenone but only 39.4 % of the patients randomized to tacrine showed an improvement in the Efficacy Index Score or at least one of the secondary outcome variables. The primary efficacy measurement was the change of the Efficacy Index Score from baseline to the assessment after 60 weeks treatment. The analysis was done on intention-to-treat (ITT) in a before-and-after test design. Patients randomized to idebenone showed a higher benefit from treatment than patients randomized to tacrine. We conclude that the benefit-risk ratio is favorable for idebenone compared to tacrine, and furthermore, that this ratio is likely to be similar when comparing idebenone to other cholinesterase inhibitors.

Full Text

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