A 24-week, double-blind, multi-center, randomised parallel group study compared the
efficacy and safety of 800 mg bid cyclandelate with placebo in patients with mild
to moderate dementia of primary degenerative or vascular origin. A total of 196 patients
entered the study, 147 patients completed treatment in adherence with the protocol.
Primary outcome measures were the cognitive score of the Alzheimer's Disease Assessment
Scale (ADAS-Cog), the subscale Instrumental Activities of Daily Living of the Nurses'
Observation Scale for Geriatric Patients (NOSGER-IADL) and the Clinical Global Impressions
of Change (CGI-C). Safety assessments included adverse events, vital signs, ECG and
clinical laboratory parameters. The primary efficacy results based on a multi-level
responder analysis including ADAS-Cog, NOSGER-IADL and CGI-C failed to demonstrate
statistical superiority of cyclandelate in comparison to placebo. The direction of
changes favored cyclandelate in each of the variables, but the differences to placebo
were small and varied considerably between patients and centers. Retrospective exploratory
analyses suggested that efficacy of cyclandelate might be dependent on the severity
of the disease. The treatment effects in favor of cyclandelate were statistically
significant in the subgroup of moderately impaired patients (MMSE at baseline < 18)
for ADAS-Cog (Ä = − 4.0 points, p = 0.015) and CGI-C (Ä = − 0.4 points, p = 0.043)
but not for NOSGER-IADL (Ä = − 1.6 points, p = 0.059). When patients were stepwise
selected for the severity of the disease according to ADAS-Cog at baseline (> 15,
> 20, > 25 points), statistical significance was reached for ADAS-Cog and NOSGER-IADL
beginning with the step ADAS-Cog > 20 points: Ä ADAS-Cog = − 3.9 points, p = 0.044;
Ä NOSGER-IADL = -1.0, p = 0.023. The treatment differences increased further with
the step ADAS-Cog > 25 points: Ä ADAS-Cog = − 7.0 points, p = 0.008; Ä NOSGER-IADL = − 1.7,
p = 0.003. Treatment differences in CGI-C increased marginally with the stepwise selection
but did not reach statistical significance. The drug was safe and well tolerated.
References
