SYN120 a Dual 5-HT6/5-HT2A Antagonist Proof of Concept Study to Evaluate Its Safety, Tolerability and Efficacy in Parkinson's Disease Dementia (SYNAPSE)

The purpose of this study placebo-controlled, randomized, double-blind study is to assess the safety and efficacy of SYN120 in patients with Parkinson's disease dementia (PDD) already treated with a stable dose of a cholinesterase inhibitor.

开始日期2014-12-22

申办/合作机构

Biotie Therapies Oy

[+3]

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项与 Landipirdine 相关的文献（医药）

2023-09-01·Parkinsonism & related disorders

Safety, tolerability, and preliminary efficacy of SYN120, a dual 5-HT6/5-HT2A antagonist, for the treatment of Parkinson disease dementia: A randomized, controlled, proof-of-concept trial.

Article

作者: Litvan, Irene ; Eberling, Jamie ; Macklin, Eric ; Videnovic, Aleksandar ; Weintraub, Daniel ; Fernandez, Hubert H ; Schwarzschild, Michael A ; Kenney, Christopher J

BACKGROUNDSYN120 is a dual serotonin receptor (5-HT6/5-HT2A) antagonist hypothesized to improve cognition and psychiatric symptoms.OBJECTIVESWe evaluated the safety, tolerability, and efficacy of SYN120 in patients with Parkinson disease dementia (PDD).METHODSIn a multicenter, double-blind, parallel-group, 16-week phase 2a proof-of-concept trial in PDD with concomitant cholinesterase inhibitor use, eligible patients were randomized to oral SYN120 (100 mg/day) or placebo. Adverse events (AEs), Unified Parkinson's Disease Rating Scale (UPDRS) scores, and discontinuations assessed safety and tolerability. The primary and key secondary efficacy measures were the Cognitive Drug Research (CDR) computerized assessment system Continuity of Attention and Quality of Episodic Memory scores. Other efficacy measures were: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC), Brief Penn Parkinson's Daily Activity Questionnaire-15 (PDAQ-15), Scales for Outcomes in Parkinson's Disease-Sleep Scale (SCOPA-Sleep), and Neuropsychiatric Inventory (NPI).RESULTSEighty-two patients were randomized to SYN120 (N = 38) or placebo (N = 44), AEs occurred in 74% and 77% of patients, and treatment discontinuation in both groups was 16%. Nausea and vomiting were more frequent, and motor symptoms (UPDRS) worsened in the SYN120 group. At week 16, the SYN120 and placebo groups did not differ significantly for any cognitive assessment. Cognitive activities of daily living (PDAQ-15) and the NPI-Apathy/Indifference scores improved nominally in the SYN120 group compared with placebo (unadjusted p = 0.029 and 0.028).CONCLUSIONSSYN120 was adequately tolerated, mild worsening of motor symptoms was noted and it did not improve cognition in PDD patients. Its potential benefits for cognitive activities of daily living and apathy warrant further study.REGISTRATIONClinicaltrials.gov as NCT02258152.

2017-05-17·ACS Chemical Neuroscience3区 · 医学

Serotonergic Approaches in Parkinson’s Disease: Translational Perspectives, an Update

3区 · 医学

Review

作者: Fox, Susan H. ; Huot, Philippe ; Sgambato-Faure, Véronique ; McCreary, Andrew C.

Parkinson's disease (PD) has long been seen as a disorder caused by degeneration of the dopaminergic system, leading to the classic motor manifestations of the disease. However, there is now overwhelming evidence that PD is more than a disease merely caused by dopamine depletion. It is well-known that a myriad of other neurotransmitters are affected by the disease process. One such neurotransmitter is serotonin (5-HT). 5-HT has been shown to play a role in several motor and nonmotor manifestations of PD, including tremor, cognition, depression and psychosis. 5-HT also seems to play a critical role in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. A breadth of preclinical studies and clinical trials have been conducted that aimed at modulating the 5-HT system in order to alleviate depression, cognitive deficits, psychosis, and dyskinesia. In this Review, we summarize recent advances in the 5-HT field in PD, but with a translational emphasis. We start by presenting a novel nonhuman primate model of PD that presents with dual dopamine and 5-HT lesions. We then present preclinical and clinical data that introduce new concepts, such as the use of biased and partial agonists, as well as molecules recently introduced to the field of PD, such as eltoprazine, pimavanserin, nelotanserin, and SYN-120, to enhance therapeutic benefit while minimizing adverse events, notably on parkinsonian disability.

Behavioral Sciences

Treatment of Parkinson’s Disease with Cognitive Impairment: Current Approaches and Future Directions

Review

作者: Sun, Chichun ; Armstrong, Melissa J.

Cognitive impairment risk in Parkinson’s disease increases with disease progression and poses a significant burden to the patients, their families and society. There are no disease-modifying therapies or preventative measures for Parkinson’s disease mild cognitive impairment (PD-MCI), or Parkinson’s disease dementia (PDD). This article reviews current and previously investigated treatments and those under investigation, including pharmacologic, non-pharmacologic and surgical procedures. There are currently no effective pharmacologic or non-pharmacologic treatments for PD-MCI. The only recommended treatment for PDD currently is rivastigmine, a cholinesterase inhibitor. Donepezil and galantamine—other cholinesterase inhibitors—are possibly useful. Memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, is considered investigational in PDD. Drug repurposing (atomoxetine, levodopa, insulin, atomoxetine for PD-MCI; ambroxol and ceftriaxone for PDD) and novel medications (SYN120, GRF6021, NYX-458 for PD-MCI; ANAVEX2-73, LY3154207, ENT-01, DAAOI-P for PDD) currently have insufficient evidence. There is growing research supporting exercise in the treatment of PD-MCI, but most non-pharmacological approaches have insufficient evidence for use in PD-MCI (cognitive rehabilitation, deep brain stimulation, transcranial direct current stimulation, transcranial ultrasound, vestibular nerve stimulation) and PDD (cognitive intervention, deep brain stimulation, transcranial alternating current stimulation, transcranial ultrasound, temporal blood brain barrier disruption). Research is needed for both disease-modifying and symptomatic treatments in PD cognitive impairment.

100 项与 Landipirdine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11157	-	-	DB16214

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
帕金森病	临床2期	-	F. Hoffmann-La Roche Ltd.	-
认知障碍	临床前	美国	Biotie Therapies Oy	-
帕金森病所致痴呆	药物发现	美国	Acorda Therapeutics, Inc.	2014-12-22

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02258152 (SYNAPSE, CTgov)	临床2期	帕金森病所致痴呆	82	Placebo (Placebo)	繭憲範夢願蓋製襯蓋簾(鬱窪餘糧窪衊衊鹹積獵) = 積餘願蓋廠顧蓋襯廠遞鹽積鬱觸廠淵餘簾繭齋 (鏇鏇淵衊積糧鹹網簾構, 齋淵築願糧網顧鬱繭壓 ~ 壓鹽築夢築鏇鹽蓋淵襯) 更多	-	2019-04-19
				SYN120 (SYN120)	繭憲範夢願蓋製襯蓋簾(鬱窪餘糧窪衊衊鹹積獵) = 遞選鬱夢衊衊鹹繭鑰網鹽積鬱觸廠淵餘簾繭齋 (鏇鏇淵衊積糧鹹網簾構, 壓鬱艱獵積繭繭糧網窪 ~ 憲艱觸膚齋築觸鹹鏇醖) 更多
MDS2018	临床2期	非典型进行性核上性麻痹	-	SYN120 100 mg daily	築築範簾餘艱淵糧鬱願(壓繭遞壓簾襯顧觸範觸) = Numerical improvements with SYN120 compared to placebo were also noted for SCOPA-SLEEP nighttime sleep (ES=0.47; p=0.05) 製選願積醖鑰築顧襯醖 (糧艱遞遞選鏇襯齋鑰獵 ) 更多	-	2018-10-05
				Placebo
SYNAPSE (MDS2018)	临床2期	非典型进行性核上性麻痹	82	SYN120 100 mg daily	(鬱鹹衊構獵選網簾淵糧) = incidence of nausea and vomiting were two-fold higher with SYN120 壓襯鹹鬱積觸構顧憲鹽 (願顧糧積願夢繭憲蓋獵 ) 更多	不佳	2018-10-05
				Placebo