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S4‐01‐02: Results from CONNECTION: A global, Phase 3 double‐blind, placebo‐controlled confirmatory trial of dimebon (latrepirdine) in patients with mild‐to‐moderate Alzheimer's disease
Author(s) -
Doody Rachelle S.,
Tariot Pierre,
Cummings Jeff,
Winblad Bengt,
Selby Bryan,
Langenberg Andria,
Seely Lynn
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.453
Subject(s) - placebo , tolerability , medicine , adverse effect , clinical trial , dementia , physical therapy , oncology , disease , pathology , alternative medicine
not available S4-01-04 PHASE IIA CLINICAL TRIAL ON ALZHEIMER’S DISEASE WITH NP12, A GSK3 INHIBITOR Teodoro del Ser, Noscira, Tres Cantos, Madrid, Spain. Contact e-mail: tdelser@noscira.com Background: Glycogen Synthase Kinase-3 (GSK-3) plays a major role in the physiopathology of Alzheimer’s disease (AD) and its inhibition is expected to slow down the neurodegenerative process. The thiadiazolidindione NP-12 (Tideglusib, Nypta ), a non-ATP competitive GSK-3 inhibitor, has been examined in a pilot, 20 week, doubleblind, placebo-controlled, randomized, escalating dose, clinical trial in AD patients. Methods: Thirty male and female mild to moderate AD patients (Mini Mental State Examination (MMSE) 16 to 26), under stable and well tolerated anticholinesterasic treatment, were orally administered escalated doses of 400, 600, 800 and 1000 mg of NP-12 or placebo (ratio 2:1) for successive periods of 4, 4, 6 and 6 weeks respectively. The Primary Objective was to evaluate the safety and tolerability of NP12 and strict criteria for dose escalation and drug withdrawal were stated. The effects of NP12 on cognition (MMSE, ADAS-cog, Word fluency), depressive mood (Geriatric Depression Scale) and Global Clinical Assessment were examined as Secondary Objectives by means of ANCOVA or Responder analyses. Results: The incidence of adverse events was similar in both treatment groups; however, they were more commonly drug-related in Active (65%) than in Placebo group (30%). Drug treatment was discontinued in 35% Active cases, mostly due to the restrictive safety rules stated in the Protocol (moderate, asymptomatic and fully reversible increases of transaminases in 30% of cases), and in 10% Placebo cases. The frequency of responders in MMSE was significantly higher in the Active group and positive effects were observed in four (MMSE, ADAS-cog, GDS and GCA) out of five efficacy variables, although the small sample size precluded to reach statistical significance. The magnitude of these effects was consistently higher in moderate cases. Conclusions: This pilot study has provided valuable safety information about treatment of AD patients with NP12. Only efficacy estimates have been obtained due to the small sample size and the dose escalating design. The current results are promising and support further more extended clinical investigations. S4-01-05 NORADRENERGIC MECHANISMS IN THE BEHAVIORAL AND COGNITIVE SYMPTOMS IN ALZHEIMER’S DISEASE Elaine R. Peskind, University of Washington School of Medicine, Seattle, WA, USA. Contact e-mail: peskind@u.washington.edu Abstract not availablenot available S4-01-06 LOCAL DELIVERY OF NGF TO BASAL FOREBRAIN IN AD PATIENTS Maria Eriksdotter Jonhagen, Karolinska Institutet, Stockholm, Sweden. Contact e-mail: maria.eriksdotter.jonhagen@ki.se