The efficacy and safety of idebenone were studied in a prospective, randomized, double-blind, placebo controlled multicentre study in 3 parallel groups of patients with 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 450 patients were randomized to either placebo (n = 153) or idebenone 90 mg tid (n = 148) or 120 mg tid (n = 149) and treated up to 12 months. The primary endpoint for the evaluation of efficacy was at month 6. Data of the month-12 assessments were considered for the evaluation of long-term treatment effects. 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. Clinical and psychometric evaluations were made at screening, at baseline, and after 1, 3, 6, 9 and 12 months of treatment. After months 6 and 12, idebenone showed statistically significant dose-dependent improvement in the primary efficacy variable ADAS-Total and in all the secondary efficacy variables. An analysis of therapy responders performed on 3 outcome measures (CGI, ADAS-Cog, NOSGER-IADL), selected to represent different levels of assessment, revealed significant dose-related superiority of idebenone with respect to placebo in each of the 3 variables and in the concordance of responses across the 3 measures. Safety results were inconspicuous on all assessments. The study results confirm the efficacy, clinical relevance and safety of idebenone in the long-term treatment of DAT.
