Cyclandelate in the treatment of patients with mild to moderate primary degenerative dementia of the Alzheimer type or vascular dementia: Experience from a placebo controlled multi-center study

A 24-week, double-blind, multi-center, randomised parallel group study comp ared the efficacy and safety of 800 mg bid cyclandelate with placebo in pat ients with mild to moderate dementia of primary degenerative or vascular or igin. A total of 196 patients entered the study, 147 patients completed tre atment in adherence with the protocol. Primary outcome measures were the co gnitive score of the Alzheimer's Disease Assessment Scale (ADAS-Cog), the s ubscale Instrumental Activities of Daily Living of the Nurses' Observation Scale for Geriatric Patients (NOSGER-IADL) and the Clinical Global impressi ons of Change (CGI-C). Safety assessments included adverse events, vital si gns, ECG and clinical laboratory parameters. The primary efficacy results b ased on a multi-level responder analysis including ADAS-Cog, NOSGER-IADL an d CGI-C failed to demonstrate statistical superiority of cyclandelate in co mparison to placebo. The direction of changes favored cyclandelate in each of the variables, but the differences to placebo were small and varied cons iderably between patients and centers. Retrospective exploratory analyses s uggested that efficacy of cyclandelate might be dependent on the severity o f the disease. The treatment effects in favor of cyclandelate were statisti cally significant in the subgroup of moderately impaired patients (MMSE at baseline < 18) for ADAS-Cog (Delta = - 4.0 points, p = 0.015) and CGI-C (De lta = - 0.4 points, p = 0.043) but not for NOSGER-IADL (Delta = - 1.6 point s, p = 0.059). When patients were stepwise selected for the severity of the disease according to ADAS-Cog at baseline (>15, >20, >25 points), statisti cal significance was reached for ADAS-Cog and NOSGER-IADL beginning with th e step ADAS-Cog >20 points: Delta ADAS-Cog=-3.9 points, p = 0.044; Delta NO SGER-IADL = -1.0, p = 0.023. The treatment differences increased further wi th the step ADAS-Cog >25 points: Delta ADAS-Cog=-7.0 points, p=0.008; Delta NOSGER- IADL=-1.7, p=0.003. Treatment differences in CGI-C increased margi nally with the stepwise selection but did not reach statistical significanc e. The drug was safe and well tolerated.