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Neuropsychophysiological Evaluation of Three Doses of S 12024-2 in Mild-to-Moderate Alzheimer’s Disease

  • Clinical Pharmacodynamics
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Summary

This study was designed to obtain early evidence that S 12024-2 has potential central pharmacological activity and cognition-enhancing properties in patients with Alzheimer’s disease (AD). This was a single centre, double-blind, crossover study employing three oral doses of S 12024-2 (50, 100, 200mg once daily) and placebo administered over 7 days (Latin square design). 12 outpatients with mild AD (Mini-Mental State Examination scores 18 to 26) were selected according to the National Institute for Neurological and Communication Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association criteria. Clinical and electrophysiological assessments were used as follows:

  • • Clinical assessment was performed using: (a) a semicomputerised battery assessing memory and attention (VDL); (b) the Clinician Interview-Based Impression of Change (CIBIC); (c) an Activities of Daily Living scale filled in by the caregiver

  • • Electrophysiological assessment was performed using Quantitative EEG (qEEG) and Event Related Potentials (ERPs).

All measures at the end of each period (day 7) were compared with baseline measures (D0). No statistically significant treatment effect was shown in any clinical assessment. However, the CIBIC showed a trend in favour of active treatment (S 12024-2 100mg >200mg >50mg >placebo). qEEG showed a significant increase in β1 and a decrease in δ activities at 200mg versus placebo (p = 0.01) indicating nonspecific stimulation of diurnal attention. ERPs showed significant treatment activity (p = 0.05) on two parameters: amplitude and latency of the Mismatch Negativity and the Processing Negativity suggesting an improvement in automatic processing. In conclusion, the study showed good clinical tolerability of S 12024-2 and preliminary evidence of a central pharmacodynamic activity.

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Authors and Affiliations

  1. Service de Neurologie 3, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

    C. Derouesné, L. Lacomblez, P. Homeyer & L. Ouss

  2. Unité CNRS 654 LENA, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

    B. Renault

  3. Service d’Explorations Fonctionnelles du SNC, Hôpital Sainte-Anne, Paris, France

    B. Gueguen

  4. Unité de Neuropsychologie, Université de Louvain, Louvain-la-Neuve, France

    M. Van der Linden

  5. IRIServier, Courbevoie, France

    E. Neuman, M. Malbezin, S. Barrandon & D. Guez

Authors
  1. C. Derouesné
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  2. B. Renault
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  3. B. Gueguen
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  4. M. Van der Linden
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  5. L. Lacomblez
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  6. P. Homeyer
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  7. L. Ouss
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  8. E. Neuman
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  9. M. Malbezin
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  10. S. Barrandon
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  11. D. Guez
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Derouesné, C., Renault, B., Gueguen, B. et al. Neuropsychophysiological Evaluation of Three Doses of S 12024-2 in Mild-to-Moderate Alzheimer’s Disease. Clin. Drug Invest. 14, 301–306 (1997). https://doi.org/10.2165/00044011-199714040-00008

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  • DOI: https://doi.org/10.2165/00044011-199714040-00008

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