Delving into the Latest Updates on MK-0249 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

H3 receptor

Mechanism

H3 receptor inverse agonists(Histamine H3 receptor inverse agonists)

Therapeutic Areas

Nervous System DiseasesRespiratory DiseasesOther Diseases+ [1]

Active Indication-

Inactive Indication

Alzheimer DiseaseAttention Deficit Disorder With HyperactivityCognitive Dysfunction+ [7]

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization-

Inactive Organization

Merck Sharp & Dohme Corp.Merck GmbH

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC23H24F3N3O2

InChIKeyDDDZBLNULGDPGA-UHFFFAOYSA-N

CAS Registry862309-06-6

This study will evaluate acute symptomatic improvements in cognitive performance in healthy elderly participants with mild-to-moderate Alzheimer's disease. A four-week pilot study will first evaluate the CogState computerized cognitive battery in participants who are not receiving treatment. After completion of the pilot study, participants will be randomized to receive Placebo, Donepezil 5 mg, MK-0249 7.5 mg, and MK-0249 25 mg. After each drug administration the participants will be given the CogState computerized cognitive battery to assess cognitive performance. The primary hypotheses are that cognitive performance in participants with Alzheimer's disease, or in healthy participants, is improved by the administration of a single oral 5 mg dose of Donepezil as compared to placebo.

Start Date06 Apr 2009

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT00620659 / TerminatedPhase 2

Phase IIa, Randomized, Double-blind, Placebo-controlled, 3-period Crossover, Adaptive Dose Design, Clinical Trial to Evaluate Safety & Efficacy of MK0249 in Treating Refractory Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea/Hypopnea Syndrome Appropriately Using nCPAP Therapy.

The purpose of this study is to determine the safety and efficacy of MK0249 in treating refractory excessive daytime sleepiness (EDS) in patients with Obstructive Sleep Apnea/Hypopnea Syndrome (OSA/HS) using nasal continuous positive airway pressure (nCPAP) therapy.

Start Date01 Feb 2008

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT00506077 / CompletedPhase 2

A Phase IIa, Randomized, Double-Blind, Placebo-Controlled, 2-Period, Cross-Over Clinical Trial to Study the Safety and Efficacy of MK0249 for the Treatment of Cognitive Impairment in Patients With Schizophrenia

The purpose of this study is to determine the safety and effectiveness of an investigational drug MK0249 for the treatment of the cognitive impairment in patients with schizophrenia.

Start Date01 Dec 2007

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with MK-0249

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100 Translational Medicine associated with MK-0249

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100 Patents (Medical) associated with MK-0249

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10

Literatures (Medical) associated with MK-0249

01 Jan 2014·Journal of Nuclear MedicineQ1 · MEDICINE

¹¹C-MK-8278 PET as a Tool for Pharmacodynamic Brain Occupancy of Histamine 3 Receptor Inverse Agonists

Q1 · MEDICINE

Article

Author: de Hoon, Jan ; Han, Lingling ; Iannone, Robert ; Van Laere, Koenraad J. ; Koole, Michel ; Mozley, David P. ; Cerchio, Kristine ; Bormans, Guy ; Van Hecken, Anne ; Plalcza, John ; Burns, Donald H. ; Renger, John ; Hamill, Terence G. ; Hargreaves, Richard J. ; Sanabria-Bohrquez, Sandra M. ; Depre, Marleen ; De Lepeleire, Inge

The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity.METHODSUsing PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y). The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further investigated in 15 healthy male volunteers (age, 18-40 y) with up to 3 PET scans and 3 subjects per dose level.RESULTSThe mean effective dose for (11)C-MK-8278 was 5.4 ± 1.1 μSv/MBq. Human brain kinetics showed rapid high uptake and fast washout. Binding potential values can be assessed using the pons as a reference region, with a test-retest repeatability of 7%. Drug RO data showed low interindividual variability per dose (mean RO SD, 2.1%), and a targeted 90% RO can be reached for both IAs at clinically feasible doses.CONCLUSION(11)C-MK-8278 is a useful novel PET radioligand for determination of human cerebral H3 receptor binding and allows highly reproducible in vivo brain occupancy of H3-targeting drugs, hereby enabling the evaluation of novel compounds in early development to select doses and schedules.

01 Oct 2013·Sleep MedicineQ3 · MEDICINE

Alertness and psychomotor performance effects of the histamine-3 inverse agonist MK-0249 in obstructive sleep apnea patients on continuous positive airway pressure therapy with excessive daytime sleepiness: a randomized adaptive crossover study

Q3 · MEDICINE

Article

Author: Thomas Roth ; Paulette Ceesay ; David Michelson ; Ellen Snyder ; Jill Hutzelmann ; W. Joseph Herring ; Kenneth Liu ; Duane Snavely ; Christopher Lines

OBJECTIVESWe aimed to evaluate the efficacy of the selective H3 receptor inverse agonist MK-0249 to treat excessive daytime sleepiness (EDS).METHODSIn this three-period, double-blind, crossover study, 125 patients (100 men, 25 women; mean age, 48.6 years) with obstructive sleep apnea receiving nasal continuous positive airway pressure therapy who had refractory EDS were randomized to 2 weeks each of daily MK-0249 (5, 8, 10, or 12 mg, adaptively assigned), modafinil 200 mg, and placebo. At baseline and after each treatment period, six maintenance of wakefulness tests (MWT) and Psychomotor Vigilance Tasks (PVT) were conducted at 2-h intervals, beginning 1h postdose (∼09:00). The Epworth sleepiness scale (ESS), Clinical Global Impression of Severity (CGIS) and Digit Symbol Substitution Test (DSST) also were assessed. The primary end point was MWT sleep latency averaged over the first four time points (MWT-early).RESULTSMWT-early mean change from baseline sleep latency at week 2 was 1.2 min for placebo, 2.1 min for MK-0249 (top two doses pooled; P>.05 vs. placebo), and 5.9 min for modafinil (P < or = .001 vs. placebo). MK-0249 showed improvements vs placebo on secondary and exploratory end points of ESS, CGIS, PVT, and DSST. Insomnia adverse events (AEs) were greater for MK-0249 (combined doses, 17.5%) than for placebo (0.9%) or modafinil (1.8%).CONCLUSIONMK-0249 did not significantly affect MWT sleep latency. However, the pattern of improvement on subjective ratings and psychomotor performance end points suggested that MK-0249 was associated with changes in aspects of cognition and performance not captured by the MWT.

01 May 2013·Schizophrenia ResearchQ2 · MEDICINE

Randomized crossover study of the histamine H3 inverse agonist MK-0249 for the treatment of cognitive impairment in patients with schizophrenia

Q2 · MEDICINE

Article

Author: Michael F. Egan ; Regina Gottwald ; Xin Zhao ; David Michelson ; Ying Zhang ; Duane Snavely ; Christopher Lines ; Lyn Harper-Mozley

BACKGROUNDCurrent antipsychotic treatments have little impact on the cognitive deficits associated with schizophrenia. It has been proposed that agents which promote histamine release may enhance cognition. We evaluated whether the H3 inverse agonist MK-0249 might improve cognitive deficits in patients with schizophrenia.METHODSOutpatients (N=55) with schizophrenia between ages 21 and 55 who were clinically stable, experienced no more than mild to moderate overall symptoms (PANSS score total 36-75), and were taking a stable dose of antipsychotic medication were randomized to MK-0249 10mg and placebo in a multi-center, randomized, double-blind, 2-period (4-weeks per period), cross-over study. The primary efficacy endpoint was the mean change from baseline at 4-weeks of treatment in the total cognitive score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. Other assessments of cognition were also performed.RESULTSA total of 46 patients completed the study. MK-0249 10mg did not demonstrate a statistically significant difference compared to placebo in the mean change from baseline in the total cognitive score on the BACS battery after 4-weeks of treatment (-0.1, 95% CI: -2.3, 2.1) or with regard to secondary measures of attention/processing speed, episodic memory, or working memory after 4-weeks of treatment. The incidence of adverse events was greater during the MK-0249 treatment period (25/52 patients, 48.1%) compared to the placebo treatment period (15/51 patients, 29.4%).CONCLUSIONMK-0249 10mg once daily was not superior to placebo in the treatment of cognitive impairment in patients with schizophrenia after 4-weeks. (Clinicaltrials.gov: NCT00506077).

100 Deals associated with MK-0249

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11910

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Excessive Daytime Sleepiness	Phase 2	-	Merck Sharp & Dohme Corp.	01 Feb 2008
Hypopnea syndrome	Phase 2	-	Merck Sharp & Dohme Corp.	01 Feb 2008
Cognitive Dysfunction	Phase 2	-	Merck Sharp & Dohme Corp.	01 Dec 2007
Paranoid Schizophrenia	Phase 2	-	Merck Sharp & Dohme Corp.	01 Dec 2007
Alzheimer Disease	Phase 2	US	Merck GmbH	-
Alzheimer Disease	Phase 2	US	Merck GmbH	-
Attention Deficit Disorder With Hyperactivity	Phase 2	US	Merck GmbH	-
Attention Deficit Disorder With Hyperactivity	Phase 2	US	Merck GmbH	-
Schizophrenia	Phase 2	US	Merck GmbH	-
Sleep Apnea Syndromes	Phase 2	US	Merck GmbH	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00620659 (Pubmed \| Sleep Med)	Phase 2	Sleep Apnea, Obstructive \| Excessive Daytime Sleepiness	125	MK-0249 (5, 8, 10, or 12 mg)	(paekpfdhpq) = Insomnia adverse events (AEs) were greater for MK-0249 (combined doses, 17.5%) than for placebo (0.9%) or modafinil (1.8%) bntrrzxknn (gkmyfjjnvz )	-	01 Oct 2013
				Modafinil 200 mg
NCT00506077 (0249-016, CTgov)	Phase 2	Cognitive Dysfunction \| Paranoid Schizophrenia	55	MK0249 (MK0249)	xlvpnspaha(qwkgthmzuc) = rwjotumswl sdaifalwfo (frvfvjntqr, cfmrokevmx - wkazxvxakm) View more	-	07 Mar 2011
				Comparator: Placebo (unspecified) (Placebo)	xlvpnspaha(qwkgthmzuc) = uxorznvbtm sdaifalwfo (frvfvjntqr, gxldirijcj - clupecyfsz) View more
NCT00475735 (0249-018, CTgov)	Phase 2	Attention Deficit Disorder With Hyperactivity	72	MK0249 (MK-0249)	ghksbpeets(hirzeagomy) = ptvmucomyw sfwgvfxkbk (ndwtmmddph, ifvlaqlygb - qvhrkifark) View more	-	10 Dec 2010
				Concerta (methylphenidate) (Concerta)	ghksbpeets(hirzeagomy) = avicgwtxyg sfwgvfxkbk (ndwtmmddph, mroctbspsq - ygvjesxlop) View more
NCT00420420 (0249-011, CTgov)	Phase 2	Alzheimer Disease	144	Comparator: Placebo (unspecified)	egjgoefkya(aqbmprbtvh) = bnzhlggynp ebcntpfjhw (antppsomua, tdlcgoyvvz - wxuxfpptti) View more	-	18 Nov 2010