Delving into the Latest Updates on Preladenant with Synapse

The purpose of this study is to evaluate the safety and preliminary efficacy of preladenant (MK-3814A) alone and in combination with pembrolizumab (MK-3475) (pembro) in participants with advanced solid tumors that have not responded to prior therapy. This study will be done in 2 parts. Part 1 will identify and confirm the recommended Phase 2 dose (RP2D) of preladenant when given alone or in combination with pembrolizumab. Part 2 of the study will determine the safety and efficacy of preladenant in combination with pembrolizumab at the RP2D in participants with select solid tumors .

Start Date27 Jun 2017

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT01465412

/ CompletedPhase 1

An Open-label, Single Dose, Oral Administration, Sequential Two Parts Study to Compare the Pharmacokinetics of SCH 420814 / MK-3814 in Subjects With Mild and Moderate Chronic Hepatic Impairment With Their Respectively Matching Healthy Volunteers

The purpose of this study is to compare the pharmacokinetics (PK) of preladenant after administration of a single 5 mg oral dose of preladenant in participants with hepatic impairment and healthy volunteers. Part 1 of this study compares healthy volunteers with participants with mild hepatic impairment. Part 2 compares healthy volunteers with participants with moderate hepatic impairment. Healthy volunteers in each part of this study are to be matched with participants with hepatic impairment by race, age, gender, and body mass index (BMI). The primary hypotheses are that in participants with mild or moderate HI, the area under the concentration-time curve from time 0 extrapolated to time of the last quantifiable concentration (AUC0-t) of preladenant is similar to that observed in matched healthy volunteers, so that the mean ratio of hepatic impaired/healthy is contained within the interval [0.50, 2.00].

Start Date10 Nov 2011

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT01323855

/ CompletedPhase 1

A Study to Assess Pharmacokinetics of Preladenant in Subjects With Chronic Renal Impairment

This is a two part study to compare the PK of preladenant administered to participants with CRI to the PK of preladenant administered to healthy participants. Part 1 will compare the PK of participants with severe CRI to healthy participants. Part 2 will compare the PK of participants with moderate CRI and participants with mild CRI to healthy participants. The primary hypotheses are that the plasma area under the concentration-time curve from time 0 to infinity after single dosing (AUC0-∞) of preladenant in participants with either severe, moderate or mild CRI is similar to that of matched healthy participants.

Start Date28 Mar 2011

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with Preladenant

Login to view more data

100 Translational Medicine associated with Preladenant

Login to view more data

100 Patents (Medical) associated with Preladenant

Login to view more data

45

Literatures (Medical) associated with Preladenant

01 Dec 2024·IBRO Neuroscience Reports

Efficacy of preladenant in improving motor symptoms in Parkinson's disease: A systematic review and meta-analysis

Review

Author: Firouz, Narges Safar ; Aziz, Mahsa ; Belbasi, Mohaddeseh ; Ghajari, Alireza ; Kohnehshahri, Ata Akhtari ; Deravi, Niloofar ; Mohammadvand, Behnaz ; Bidares, Matin ; Janeshin, Kimia ; Naziri, Mahdyieh ; Darvishi, Afra ; Etemadi, Mohammad Hossein ; Motlagh, Hossein Ashkpour ; Asgarzadeh, Shafagh ; Mazhari, Seyed Amirhossein ; Khademi, Reza ; Abbasalizadeh, Mohammad ; Karimi, Mohammad Amin ; Sadat-Madani, Sayedeh-Fatemeh ; Shendi, Zahra Jafari

BackgroundParkinson's disease (PD) is a complex neurodegenerative disorder characterized by dopamine depletion and severe motor impairments. Preladenant, an adenosine A2 receptor antagonist, is an investigational treatment for PD. This systematic review and meta-analysis aimed to critically evaluate the efficacy of Preladenant in improving motor symptoms in patients with PD.MethodsA comprehensive literature search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to March 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing Preladenant with placebo in PD patients were included. The primary outcome was the change in daily ON time without troublesome dyskinesia. Secondary outcomes included the change in daily OFF time and adverse events. The risk of bias was assessed using the Cochrane Risk of Bias tool.ResultsFour RCTs with a total of 2097 PD patients were included. Pooled analysis showed that Preladenant could generally increase daily ON time (pooled effect 0.15 and 95 % CI: -0.19-0.48) and reduce daily OFF time (pooled effect -0.04 and 95 % CI: -0.43-0.36) compared to placebo, however it was not significant. The included studies had moderate to high heterogeneity. No significant differences in adverse events were observed between Preladenant and placebo.ConclusionThis meta-analysis suggests that Preladenant may improve motor fluctuations in PD patients by increasing ON time and reducing OFF time. However, the high heterogeneity among studies warrants further large-scale, high-quality RCTs to confirm these findings and establish the long-term safety and efficacy of Preladenant in PD management.

03 Jul 2023·Pharmaceutical Development and Technology

Combination immunotherapy of PEG-modified preladenant thermosensitive liposomes and PD-1 inhibitor effectively enhances the anti-tumor immune response and therapeutic effects

Article

Author: Zhou, Jianwen ; Sui, Xiaoyu ; Ma, Xiaoxing ; Han, Cuiyan ; Zhu, Wenquan ; Tong, Yao

Immunotherapy is a promising cancer treatment strategy. In contrast, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors are associated with low response rates and are only useful in a small group of cancer patients. A combination of treatments may be effective for overcoming this clinical issue. Preladenant is an adenosine (ADO) receptor inhibitor that can block the ADO pathway and improve the tumor microenvironment (TME), thereby enhancing the immunotherapeutic effect of PD-1 inhibitors. However, its poor water solubility and low targeting limit its clinical applications. We designed a PEG-modified thermosensitive-liposome (pTSL) loaded with ADO small molecule inhibitor preladenant (P-pTSL) to overcome these problems and enhance the effect of PD-1 inhibitor on breast cancer immunotherapy. The prepared P-pTSL was round and uniformly distributed with a particle size of (138.9 ± 1.22) nm, PDI: 0.134 ± 0.031, and zeta potential (-10.1 ± 1.63) mV; preladenant was released slowly at 37 °C but released fast at 42 °C from P-pTSL, which was 76.52 ± 0.44%. P-pTSL has good long-term and serum stability and excellent tumor-targeting ability in mice. Moreover, the combination with PD-1 inhibitor significantly enhanced the anti-tumor effect, and the improvement of related factors in serum and lymph was more obvious under the condition of 42 °C thermotherapy in vitro.

23 May 2022·Angewandte Chemie International EditionQ1 · CHEMISTRY

Single Stabilizing Point Mutation Enables High‐Resolution Co‐Crystal Structures of the Adenosine A_2A Receptor with Preladenant Conjugates

Q1 · CHEMISTRY

Article

Author: Voß, Jan H. ; Tiruttani Subhramanyam, Udaya K. ; Labahn, Jörg ; Vaaßen, Victoria J. ; Claff, Tobias ; Schlegel, Jonathan G. ; Klapschinski, Tim A. ; Müller, Christa E. ; Vielmuth, Christin

AbstractThe G protein‐coupled adenosine A2A receptor (A2AAR) is an important new (potential) drug target in immuno‐oncology, and for neurodegenerative diseases. Preladenant and its derivatives belong to the most potent A2AAR antagonists displaying exceptional selectivity. While crystal structures of the human A2AAR have been solved, mostly using the A2A‐StaR2 protein that bears 9 point mutations, co‐crystallization with Preladenant derivatives has so far been elusive. We developed a new A2AAR construct harboring a single point mutation (S913.39K) which renders it extremely thermostable. This allowed the co‐crystallization of two novel Preladenant derivatives, the polyethylene glycol‐conjugated (PEGylated) PSB‐2113, and the fluorophore‐labeled PSB‐2115. The obtained crystal structures (2.25 Å and 2.6 Å resolution) provide explanations for the high potency and selectivity of Preladenant derivatives. They represent the first crystal structures of a GPCR in complex with PEG‐ and fluorophore‐conjugated ligands. The applied strategy is predicted to be applicable to further class A GPCRs.

100 Deals associated with Preladenant

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D09717	Preladenant	-	DB11864

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Young onset Parkinson disease	Phase 2	-	Merck Sharp & Dohme Corp.	06 Jul 2010
Akathisia, Drug-Induced	Phase 2	-	Merck Sharp & Dohme Corp.	10 Jul 2006
Dyskinesia, Drug-Induced	Phase 2	-	Merck Sharp & Dohme Corp.	10 Jul 2006
Schizoaffective disorder	Phase 2	-	Merck Sharp & Dohme Corp.	10 Jul 2006
Schizophrenia	Phase 2	-	Merck Sharp & Dohme Corp.	10 Jul 2006
Parkinson Disease	Phase 2	CA	Merck GmbH	-
Parkinson Disease	Phase 2	US	Merck GmbH	-
Parkinson Disease	Phase 2	EU	Merck GmbH	-
Parkinson Disease	Phase 2	TR	Merck GmbH	-
Parkinson Disease	Phase 2	IL	Merck GmbH	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03099161 (3814A-062 \| MK-3814A-062, CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	10	preladenant	axtkoavutm(ozzuvhlsgs) = pfhbccsnmm mfblxjgxss (tuvtbwujpu, hfohrzvrha - illohqbvid) View more	-	05 Jun 2019
NCT00693472 (P05145, CTgov)	Phase 2	Akathisia, Drug-Induced \| Psychotic Disorders	46	Preladenant+Anticholinergic agents or propanolol+Haloperidol (Part 1: Preladenant)	uuclurhvch(eezjxntxif) = nutjceqhkr bqlkypkiwv (pmagfkivlw, fwvxotcger - enimpxtoqx) View more	-	24 May 2017
				Placebo+Anticholinergic agents or propanolol+Haloperidol (Part 1: Placebo)	uuclurhvch(eezjxntxif) = dbnzbhgobt bqlkypkiwv (pmagfkivlw, jxuizlgufx - ziqqdqmlwp) View more
NCT00406029 (P04501, CTgov)	Phase 2	Dyskinesia, Drug-Induced \| Motor Disorders \| Parkinson Disease	253	Other Parkinson's Disease treatments+Preladenant+L-DOPA (Preladenant 1 mg BID)	tgajcnowrd(ryhostvatw) = hdbxnjjjmq balcxahvpr (sufgduzdqc, afwydsvkny - zuokmuwgrt) View more	-	08 Feb 2017
				Other Parkinson's Disease treatments+Preladenant+L-DOPA (Preladenant 2 mg BID)	tgajcnowrd(ryhostvatw) = dcegrywvvj balcxahvpr (sufgduzdqc, fgmceesdht - zthvgihfuy) View more
NCT01215227 (P06153, CTgov)	Phase 3	Parkinson Disease	839	Placebo to rasagiline+Preladenant (Preladenant 2 mg)	smmkgcnafv(bwgclgnzin) = pjdzotrxnf zwxbzsaycy (ccuowpfxlu, cxpvuhojwm - zokjkjchyw) View more	-	12 Dec 2016
				Placebo to rasagiline+Preladenant (Preladenant 5 mg)	smmkgcnafv(bwgclgnzin) = kzqnctyrcn zwxbzsaycy (ccuowpfxlu, xtoiahkopm - zjhwioeibs) View more
NCT00537017 (P05175, CTgov)	Phase 2	Parkinson Disease	140	Other Parkinson's Disease treatments+Preladenant+L-DOPA	tvfalnafuc(fkwzykoewy) = mqqrgvvncv nzbsdqvame (xkvmfoqkdd, cnguutedjw - qhrtkqbwgb) View more	-	06 Dec 2016
NCT01294800 (Pubmed \| Parkinsonism Relat Disord)	Phase 2	Parkinson Disease	111	Preladenant 2 mg	gwtdwevlwb(alngtwrzxt) = zelmaglxow hlmmivesds (cgagwxcmxw )	Negative	01 Nov 2016
				Preladenant 5 mg	gwtdwevlwb(alngtwrzxt) = biezgamohn hlmmivesds (cgagwxcmxw )
NCT01294800 (P06402, CTgov)	Phase 2	Parkinson Disease	450	Preladenant (Preladenant 2 mg)	iwmllpnxiw(omywyshhdu) = hspfbomsdn vtebbplisq (ahizyuianw, zsojhajrpx - pcdqdayjoz) View more	-	11 Oct 2016
				Preladenant (Preladenant 5 mg)	iwmllpnxiw(omywyshhdu) = oiaymywghr vtebbplisq (ahizyuianw, lpvlahylhe - pwhwrfsedh) View more
WPC2016	Not Applicable	Parkinson Disease	-	Istradefylline 20 mg/day	ovdjbyvgya(zyqszucksu) = wwsetzrceg pejmvxuldf (zjaozccpab, -1.130 to 0.155) View more	-	01 Sep 2016
				Istradefylline 40 mg/day	ovdjbyvgya(zyqszucksu) = occmyvkirs pejmvxuldf (zjaozccpab, -1.301 to 0.263) View more