Name: PF-05212377
Synonyms: PF-5212377, WYE-103760, SAM-760
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Inactive)
Company: Pfizer


SAM-760 is an orally available antagonist of the serotonin 6 receptor (5-HT6). By modulating serotonin levels in the brain, 5-HT6 antagonists are thought to lead to secondary increases in the levels of the neurotransmitters acetylcholine and glutamate, benefitting learning and memory. Wyeth originally developed PF 5212377 as WYE 103760, also known as as SAM 760, before becoming a subsidiary of Pfizer in 2009.


Between 2009 and 2014, Wyeth and then Pfizer conducted four Phase 1 trials of PF-05212377 in about 230 healthy volunteers. One trial, conducted in France, evaluated the effect of a single dose of PF 5212377 on scopolamine-induced cognitive impairments for its ability to improve performance in the Groton Maze Learning Task. Also in France, a multiple-ascending-dose study assessed safety, tolerability, and pharmacokinetics of once-daily dosing for 14 days, and a similar study evaluated ascending single doses of PF 5212377. A U.S. trial using positron emission tomography (PET) correlated plasma drug levels and 5-HT6 receptor binding in the brain following a single dose.

In November 2012, Pfizer initiated a Phase 2 study to assess the efficacy of a 30 mg capsule of PF 5212377, taken once daily, in mild to moderate Alzheimer's patients with neuropsychiatric symptoms who are on a stable dose of donepezil (NCT01712074). Change on the ADAS-cog 13 was the primary outcome measure, change on the NPI the secondary outcome. This trial was intended to enroll 342 patients from the United States, but stopped after 186. In October 2015, Pfizer terminated this study because a futility analysis indicated lack of efficacy. 

In November 2013, Pfizer started a Phase 1 study in 4 healthy volunteers to determine 5HT6 receptor occupancy levels achieved with single oral doses of 70 mg of PF 5212377 and less. News coverage of the trial's termination included claims of receptor occupancy needed to achieve efficacy (see Feb 2016 FierceBiotech story).

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026
Pfizer NCT01712074


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External Citations

  1. NCT01712074
  2. FierceBiotech

Further Reading

No Available Further Reading