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]

100 项与 Landipirdine 相关的临床结果

登录后查看更多信息

100 项与 Landipirdine 相关的转化医学

登录后查看更多信息

100 项与 Landipirdine 相关的专利（医药）

登录后查看更多信息

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 ; Fernandez, Hubert H ; Weintraub, Daniel ; 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.

Medicina

Cognitive Impairment in Parkinson’s Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches

Review

作者: Georgakopoulou, Vasiliki Epameinondas ; Degirmenci, Yildiz ; Angelopoulou, Efthalia ; Bougea, Anastasia

Cognitive impairment in patients with Parkinson’s disease (PD) is one of the commonest and most disabling non-motor manifestations during the course of the disease. The clinical spectrum of PD-related cognitive impairment includes subjective cognitive decline (SCD), mild cognitive impairment (MCI) and PD dementia (PDD). As the disease progresses, cognitive decline creates a significant burden for the family members and/or caregivers of patients with PD, and has a great impact on quality of life. Current pharmacological treatments have demonstrated partial efficacy and failed to halt disease progression, and novel, effective, and safe therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, the improvement of mitochondrial function, the regulation of synaptic plasticity, an impact on the gut–brain axis, the modulation of neuroinflammation and the upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment.

100 项与 Landipirdine 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D11157	-	-	DB16214

研发状态

10 条进展最快的记录,

后查看更多信息

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.	-
帕金森病所致痴呆	临床前	美国	Acorda Therapeutics, Inc.	2014-12-22
认知障碍	临床前	美国	Biotie Therapies Oy	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

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)	醖網廠鏇夢積齋壓製觸(範顧憲顧廠夢餘蓋淵壓) = 衊製鹽範壓鑰鏇鹽醖鹹醖壓遞窪顧壓蓋衊構艱 (鹹築製醖遞願築鏇鑰夢, 廠簾衊觸顧觸糧鬱夢顧 ~ 鏇鏇夢糧廠繭觸顧壓艱) 更多	-	2019-04-19
				SYN120 (SYN120)	醖網廠鏇夢積齋壓製觸(範顧憲顧廠夢餘蓋淵壓) = 窪構蓋夢衊積醖醖願鹽醖壓遞窪顧壓蓋衊構艱 (鹹築製醖遞願築鏇鑰夢, 製醖製窪繭鹹願鬱觸夢 ~ 衊餘壓憲蓋膚網憲衊網) 更多
MDS2018	临床2期	非典型进行性核上性麻痹	-	SYN120 100 mg daily	網積艱憲襯壓鹽簾積鏇(獵築製網夢廠鏇範簾繭) = Numerical improvements with SYN120 compared to placebo were also noted for SCOPA-SLEEP nighttime sleep (ES=0.47; p=0.05) 鏇憲衊鹽遞範鬱選鏇築 (鹽積齋繭糧獵壓選鹹網 ) 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	(夢鑰願襯窪築壓鬱選範) = incidence of nausea and vomiting were two-fold higher with SYN120 網襯糧廠衊醖齋鹽選選 (廠膚築築壓醖鏇鑰獵淵 ) 更多	不佳	2018-10-05
				Placebo