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J Alzheimers Dis. 2017;58(4):1217-1228. doi: 10.3233/JAD-161309.

Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD).

Author information

1
Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Switzerland.
2
Department of Neurology, Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
3
Memory Clinic ofFundació ACE, Institut Catalá de Neurociències Aplicades, Barcelona, Spain.
4
Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany.
5
RocheSafety Risk Management, Licensing & Early Development, RocheInnovation Center, NY, USA.
6
Roche Product Development, Roche Innovation Center, NY, USA.
7
Roche Products Limited, Roche Innovation Center Welwyn, Welwyn Garden City, UK.
8
Roche Product Development Neuroscience, Roche Innovation Center Basel, F.Hoffmann-La Roche Ltd, Switzerland.
9
Genentech Inc., Product Development Neuroscience, South San Francisco, CA, USA.

Abstract

BACKGROUND:

Sembragiline is a potent, selective, long-acting, and reversible MAO-B inhibitor developed as a potential treatment for Alzheimer's disease (AD).

OBJECTIVE:

To evaluate the safety, tolerability, and efficacy of sembragiline in patients with moderate AD.

METHODS:

In this Phase II study (NCT01677754), 542 patients with moderate dementia (MMSE 13-20) on background acetylcholinesterase inhibitors with/without memantine were randomized (1:1:1) to sembragiline 1 mg, 5 mg, or placebo once daily orally for 52 weeks.

RESULTS:

No differences between treated groups and placebo in adverse events or in study completion. The primary endpoint, change from baseline in ADAS-Cog11, was not met. At Week 52, the difference between sembragiline and placebo in ADAS-Cog11 change from baseline was - 0.15 (p = 0.865) and 0.90 (p = 0.312) for 1 and 5 mg groups, respectively. Relative to placebo at Week 52 (but not at prior assessment times), the 1 mg and 5 mg sembragiline groups showed differences in ADCS-ADL of 2.64 (p = 0.051) and 1.89 (p = 0.160), respectively. A treatment effect in neuropsychiatric symptoms (as assessed by the difference between sembragiline and placebo on BEHAVE-AD-FW) was also seen at Week 52 only: - 2.80 (p = 0.014; 1 mg) and - 2.64 (p = 0.019; 5 mg), respectively. A post hoc subgroup analysis revealed greater treatment effects on behavior and functioning in patients with more severe baseline behavioral symptoms (above the median).

CONCLUSIONS:

This study showed that sembragiline was well-tolerated in patients with moderate AD. The study missed its primary and secondary endpoints. Post hoc analyses suggested potential effect on neuropsychiatric symptoms and functioning in more behaviorally impaired study population at baseline.

KEYWORDS:

Alzheimer’s disease; Phase II clinical trial; dementia; monoamine oxidase B

PMID:
28550255
PMCID:
PMC5523913
DOI:
10.3233/JAD-161309
[Indexed for MEDLINE]
Free PMC Article

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