Sustained efficacy and safety of idebenone in the
treatment of Alzheimer's disease: update on a 2-year double-blind multicentre
Gutzmann H, Hadler D.
Abteilung fur Gerontopsychiatrie
Berlin, Federal Republic of Germany
J Neural Transm Suppl 1998;54:301-10
- The 2-year efficacy and safety of idebenone
were studied in a prospective, randomized, double-blind multicentre study in
3 parallel groups of patients with dementia of the Alzheimer type (DAT) of
mild to moderate degree. A total of 450 patients were randomized to
either placebo for 12 months, followed by idebenone
90 mg tid for another 12
months (n = 153) or idebenone 90 mg tid for 24 months (n = 148) or 120 mg
tid for 24 months (n = 149). The primary outcome measure was the total score
of the Alzheimer's Disease Assessment Scale (ADAS-Total) at month 6.
Secondary outcome measures were the ADAS cognitive (ADAS-Cog) and
noncognitive score (ADAS-Noncog), the clinical global response
(CGI-Improvement), the SKT neuropsychological test battery, and the Nurses'
Observation Scale for Geriatric Patients (NOSGER-Total and IADL subscale).
Safety parameters were adverse events, vital signs, ECG and clinical
laboratory parameters. During the placebo controlled period (the first year
of treatment), idebenone showed statistically significant
dose-dependent improvement in the primary efficacy variable ADAS-Total and
in all the secondary efficacy variables. There was no evidence for a loss of
efficacy during the second year of treatment, as a further improvement of
most efficacy variables was found in the second year in comparison to the
results at the 12 months visit. Also, a clear dose effect relationship
(placebo/90 mg < idebenone 90 mg < idebenone 120 mg) was maintained
throughout the second year of treatment. This suggests that idebenone
exerts its beneficial therapeutic effects on the course of the disease by
slowing down its progression. Safety and tolerability of idebenone
were good and similar to placebo during the first year of treatment and did
not change during the second year.