Neuroscience
A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease.
Neurology. 2011 Sep 14;
Authors: Salloway S, Sperling R, Keren R, Porsteinsson AP, van Dyck CH, Tariot PN, Gilman S, Arnold D, Abushakra S, Hernandez C, Crans G, Liang E, Quinn G, Bairu M, Pastrak A, Cedarbaum JM.
Abstract
OBJECTIVE:This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD). METHODS:A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n = 84) to placebo (n = 82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups. RESULTS:The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p = 0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF Aβx-42 was decreased significantly compared to placebo (p = 0.009). CONCLUSIONS:Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD.Classification of evidence:Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005.
PMID: 21917766 [PubMed - as supplied by publisher]
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Neuroscience
Neuropsychology Abstract of the Day: Alzheimer's Disease
A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease.
Neurology. 2011 Sep 14;
Authors: Salloway S, Sperling R, Keren R, Porsteinsson AP, van Dyck CH, Tariot PN, Gilman S, Arnold D, Abushakra S, Hernandez C, Crans G, Liang E, Quinn G, Bairu M, Pastrak A, Cedarbaum JM.
Abstract
OBJECTIVE:This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD). METHODS:A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n = 84) to placebo (n = 82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups. RESULTS:The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p = 0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF Aβx-42 was decreased significantly compared to placebo (p = 0.009). CONCLUSIONS:Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD.Classification of evidence:Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005.
PMID: 21917766 [PubMed - as supplied by publisher]
- Alzheimer Disease: Targacept's Failed Tc-1734 Phase 2b Trial
From a Targacept press release:Targacept Phase 2b Clinical Trial in Alzheimer’s Disease Does Not Show Superiority of TC-1734 Over Donepezil July 14, 2014 "Winston-Salem, NC – Targacept, Inc. (NASDAQ: TRGT), a clinical-stage biopharmaceutical company...
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Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study of the Oral γ-Secretase Inhibitor BMS-708163 (Avagacestat): Tolerability Profile, Pharmacokinetic Parameters, and Pharmacodynamic Markers Clin Ther. 2012 Feb 28; Tong...
- Neuropsychology Abstract Of The Day: Simvastatin Clinical Trial In Alzheimer's Disease
A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology. 2011 Aug 9;77(6):556-63 Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, Aisen PS Abstract BACKGROUND: Lowering cholesterol is associated...
- Alzheimer Disease: Dimebon Results
A press release from earlier today by Pfizer: Pfizer And Medivation Announce Results From Two Phase 3 Studies In Dimebon (latrepirdine) Alzheimer’s Disease Clinical Development Program [snip] "About the CONNECTION Study "CONNECTION is a Phase 3, multi-national,...
- Abstract Of The Day: Alzheimer Disease Drug Treatments
Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25; (1): CD005593. BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI) in 1997, most clinicians and probably most patients...