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8 Diseases |  |
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23 News |  |
- ||| MK-7622 / Merck (MSD)
Journal, Adverse events: Investigating Drivers for M Muscarinic Acetylcholine Receptor-Mediated Adverse Events by M Positive Allosteric Modulators. (Pubmed Central) - May 14, 2022
Gα , Gα and b-arrestin 1/2 influence binding affinity and functional properties for both ACh and M PAMs. These transductors affect M PAMs with observed AEs more than the M PAM without AEs, VU0486846, and thus playing a potential role in driving AEs.
- ||| donepezil / Generic mfg.
Journal, Adverse events: T-495, a novel low cooperative M receptor positive allosteric modulator, improves memory deficits associated with cholinergic dysfunction and is characterized by low gastrointestinal side effect risk. (Pubmed Central) - Oct 27, 2020
Here, we describe the pharmacological characteristics of a novel low cooperative M R PAM T-495 (α-value of 170), using the clinically tested higher cooperative M R PAM MK-7622 (α-value of 511) as a control...Additionally, in mice with reduced acetylcholine levels in the forebrain via overexpression of A53T α-synuclein (ie, a mouse model of dementia with Lewy bodies and Parkinson's disease with dementia), T-495, like donepezil, reversed the memory deficits in the contextual fear conditioning test and Y-maze task. Thus, low cooperative M R PAMs are promising agents for the treatment of memory deficits associated with cholinergic dysfunction.
- || risperidone / Generic mfg., Egis
Clinical, Journal: A novel M1 PAM VU0486846 exerts efficacy in cognition models without displaying agonist activity or cholinergic toxicity. (Pubmed Central) - Dec 21, 2019
These findings further strengthen the argument that compounds with modest in vitro M1 PAM activity (EC50s > 100 nM) and pure-PAM activity in native tissues display robust pro-cognitive efficacy without AEs mediated by excessive activation of M1. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.
- | MK-7622 / Merck (MSD)
Preclinical, Journal: Preclinical to Human Translational Pharmacology of the Novel MPositive Allosteric Modulator MK-7622. (Pubmed Central) - Oct 16, 2019
Additionally, there were differences in the spectral power changes produced by MK-7622 in rhesus vs. human. In sum, these results are the first to demonstrate translation of preclinical cognition and target modulation to clinical effects in man for a selective M1 muscarinic receptor positive allosteric modulator.
- MK-7622 / Merck (MSD)
Phase classification: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Aug 17, 2016
P2a/2b, N=240, Terminated, Sponsor: Merck Sharp & Dohme Corp.
In sum, these results are the first to demonstrate translation of preclinical cognition and target modulation to clinical effects in man for a selective M1 muscarinic receptor positive allosteric modulator. Phase classification: P2a --> P2a/2b
- | MK-7622 / Merck (MSD)
Enrollment change, Trial termination: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Apr 19, 2016
P2a, N=240, Terminated, Sponsor: Merck Sharp & Dohme Corp.
N=830 --> 240 | Active, not recruiting --> Terminated; Stage 1 interim analysis of efficacy met the criteria for early trial termination (futility). The trial was terminated at Stage 1; did not proceed to Stage 2.
- || MK-7622 / Merck (MSD)
Trial primary completion date: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Mar 25, 2016
P2a, N=830, Active, not recruiting, Sponsor: Merck Sharp & Dohme Corp.
The trial was terminated at Stage 1; did not proceed to Stage 2. Trial primary completion date: Apr 2018 --> Apr 2016
- ||| MK-7622 / Merck (MSD)
Enrollment closed: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Mar 4, 2016
P2a, N=830, Active, not recruiting, Sponsor: Merck Sharp & Dohme Corp.
Trial primary completion date: Apr 2018 --> Apr 2016 Recruiting --> Active, not recruiting
- || MK-7622 / Merck (MSD)
Trial primary completion date: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Jan 17, 2016
P2a, N=830, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Recruiting --> Active, not recruiting Trial primary completion date: Dec 2019 --> Apr 2018
- || MK-7622 / Merck (MSD)
Trial primary completion date: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Oct 23, 2015
P2a, N=830, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Trial primary completion date: Dec 2019 --> Apr 2018 Trial primary completion date: Apr 2020 --> Dec 2019
- || MK-7622 / Merck (MSD)
Trial primary completion date: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Jan 22, 2015
P2a, N=830, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Trial primary completion date: Apr 2020 --> Dec 2019 Trial primary completion date: Aug 2017 --> Apr 2020
- |||| MK-7622 / Merck (MSD)
Enrollment open: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Nov 4, 2013
P2a, N=830, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Trial primary completion date: Aug 2017 --> Apr 2020 Not yet recruiting --> Recruiting
- ||| MK-7622 / Merck (MSD)
Enrollment change: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Sep 29, 2013
P2a, N=830, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
Not yet recruiting --> Recruiting N=640 --> 830
- ||| MK-7622 / Merck (MSD)
Trial initiation date: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - Jul 8, 2013
P2a, N=830, Recruiting, Sponsor: Merck Sharp & Dohme Corp.
N=640 --> 830 Initiation date: May 2013 --> Oct 2013
- ||||| MK-7622 / Merck (MSD)
New P2a trial: Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (clinicaltrials.gov) - May 9, 2013
P2a, N=830, Recruiting, Sponsor: Merck Sharp & Dohme Corp.