Abstract
Background: This randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of the 5-HT6 receptor antagonist, SB-742457, in subjects with mild-to-moderate probable Alzheimers disease (AD). Methods: Participating subjects had a Mini-Mental State Examination (MMSE) score of 12 to 26 after a 4-week, single-blind, placebo run-in phase, and were randomized (2:1:1:2) to receive placebo, SB-742457 5 mg, 15 mg, or 35 mg once daily for 24 weeks. Coprimary efficacy endpoints were the Clinicians Interview-Based Impression of Change with caregiver input (CIBIC+) score and change from baseline in Alzheimers Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score at Week 24, in the intent-to-treat (ITT) population. A model-based design provided 90% power to detect a linear trend in treatment response across increasing doses and ≥90% power to compare SB-742457 35 mg with placebo. Results: 371 subjects were randomized. In the ITT population (n=357), linear trend analysis at Week 24 suggested a dose response for CIBIC+ with a mean slope of -0.05 points/5-mg dose increase (95% confidence interval [CI]: -0.09, -0.01; p=0.016). The dose response slope for change from baseline in ADAS-Cog was -0.22 points/5-mg dose increase (95% CI: -0.45, 0.01; p=0.059). The adjusted mean treatment difference from placebo at Week 24 for SB-742457 35 mg (-0.31) was significant on CIBIC+ (95% CI: -0.62, -0.00; p=0.047) but non-significant on ADAS-Cog (-1.28 [95% CI: -2.96, 0.40]; p=0.135). Adverse events occurred in 24-37% in the SB-742457 groups vs 29% for placebo; 11-16% discontinued SB- 742457 vs 15% for placebo. Comments: SB-742457 was generally safe and well tolerated and may be efficacious in AD.
Keywords: SB-742457, Alzheimer's disease, serotonin, 5-HT6, cognition, global function
Current Alzheimer Research
Title: Double-Blind, Controlled Phase II Study of a 5-HT6 Receptor Antagonist, SB-742457, in Alzheimers Disease
Volume: 7 Issue: 5
Author(s): G. Maher-Edwards, M. Zvartau-Hind, A.J. Hunter, M. Gold, G. Hopton, G. Jacobs, M. Davy and P. Williams
Affiliation:
Keywords: SB-742457, Alzheimer's disease, serotonin, 5-HT6, cognition, global function
Abstract: Background: This randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of the 5-HT6 receptor antagonist, SB-742457, in subjects with mild-to-moderate probable Alzheimers disease (AD). Methods: Participating subjects had a Mini-Mental State Examination (MMSE) score of 12 to 26 after a 4-week, single-blind, placebo run-in phase, and were randomized (2:1:1:2) to receive placebo, SB-742457 5 mg, 15 mg, or 35 mg once daily for 24 weeks. Coprimary efficacy endpoints were the Clinicians Interview-Based Impression of Change with caregiver input (CIBIC+) score and change from baseline in Alzheimers Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score at Week 24, in the intent-to-treat (ITT) population. A model-based design provided 90% power to detect a linear trend in treatment response across increasing doses and ≥90% power to compare SB-742457 35 mg with placebo. Results: 371 subjects were randomized. In the ITT population (n=357), linear trend analysis at Week 24 suggested a dose response for CIBIC+ with a mean slope of -0.05 points/5-mg dose increase (95% confidence interval [CI]: -0.09, -0.01; p=0.016). The dose response slope for change from baseline in ADAS-Cog was -0.22 points/5-mg dose increase (95% CI: -0.45, 0.01; p=0.059). The adjusted mean treatment difference from placebo at Week 24 for SB-742457 35 mg (-0.31) was significant on CIBIC+ (95% CI: -0.62, -0.00; p=0.047) but non-significant on ADAS-Cog (-1.28 [95% CI: -2.96, 0.40]; p=0.135). Adverse events occurred in 24-37% in the SB-742457 groups vs 29% for placebo; 11-16% discontinued SB- 742457 vs 15% for placebo. Comments: SB-742457 was generally safe and well tolerated and may be efficacious in AD.
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Cite this article as:
Maher-Edwards G., Zvartau-Hind M., Hunter A.J., Gold M., Hopton G., Jacobs G., Davy M. and Williams P., Double-Blind, Controlled Phase II Study of a 5-HT6 Receptor Antagonist, SB-742457, in Alzheimers Disease, Current Alzheimer Research 2010; 7 (5) . https://dx.doi.org/10.2174/156720510791383831
DOI https://dx.doi.org/10.2174/156720510791383831 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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