PF-05212377 / Pfizer - LARVOL DELTA

Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders. (PubMed, Biomolecules) - "Several 5-HT receptor antagonists (idalopirdine, intepirdine and latrepirdine) showed efficacy in alleviating cognitive deficits associated with AD in the proof-of-concept clinical studies; however, the outcomes of the subsequent phase 3 studies were largely disappointing...Masupirdine, a selective 5-HT receptor antagonist, reduced agitation/aggression-like behaviors in animal models, and a post hoc analysis of a phase 2 trial suggested potential beneficial effects on agitation/aggression and psychosis in AD. This agent will be assessed in additional trials, and the outcome of the trials will inform the use of 5-HT receptor antagonists in the treatment of agitation in dementia of the Alzheimer's type."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Psychiatry • Schizophrenia

Investigating CNS distribution of PF-05212377, a P-glycoprotein substrate, by translation of 5-HT receptor occupancy from non-human primates to humans. (PubMed, Biopharm Drug Dispos) - P1 | "In humans, PF-05212377 demonstrated dose and concentration dependent increases in 5-HT RO; maximal 5-HT6 RO of ?80% was measured in humans at doses of ?15 mg with an estimated unbound plasma EC of 0.37 nM (which was similar to the in vitro human 5HT6 binding K 0.32 nM). In conclusion, cumulative evidence from NHP and human PET RO assessments confirmed that NHP is more appropriate than rat for the prediction of human brain penetration of PF-05212377, a P-gp/non-BCRP substrate."

Journal • Alzheimer's Disease • CNS Disorders

Study Evaluating TheSafety And Efficacy Of PF-05212377 Or Placebo In Subjects With Alzheimer's Disease With Existing Neuropsychiatric Symptoms On Donepezil (clinicaltrials.gov) - P2; N=342; Recruiting; Sponsor: Pfizer; Trial primary completion date: Dec 2016 ->Sep 2015

Trial primary completion date • Alzheimer's Disease • Biosimilar

A Phase 2 clinical trial of PF-05212377 (SAM-760) in subjects with mild to moderate Alzheimer's disease with existing neuropsychiatric symptoms on a stable daily dose of donepezil. (PubMed, Alzheimers Res Ther) - P2; "SAM-760 was safe and well tolerated, but there was no benefit of SAM-760 on measures of cognition, neuropsychiatric symptoms, or daily function. Differences in trial design, study population, region, or pharmacological profile may explain differences in outcome compared with other 5-HTreceptor antagonists."

Clinical • Journal • P2 data