Evidence map›Paper›PMID 29622037›Full record

Trial reportAlzheimer's research & therapy2018

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.

Terence Fullerton, Brendon Binneman, William David, Marielle Delnomdedieu, James Kupiec, Peter Lockwood, Jessica Mancuso, Jeffrey Miceli, Joanne Bell

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01712074 (A Randomized, 18-week, Placebo-controlled, Double-blind, Parallel Group Study Of The Safety And Efficacy Of Pf-05212377), which is not on this map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01712074 phase2terminatednot on this map

A Randomized, 18-week, Placebo-controlled, Double-blind, Parallel Group Study Of The Safety And Efficacy 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

TypeinterventionalSponsorPfizerRan2012 to 2015Enrolled186ConditionsAlzheimer's DiseaseArmsPF-05212377 (SAM-760), Placebo
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. PolyfunctionalizedInternational journal of molecular sciences · 2026
    Article
  4. Review
  5. Review
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  9. Article
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  11. Review
  12. Molecules (Basel, Switzerland) · 2021
    Article
  13. Sulfur-containing therapeutics in the treatment of Alzheimer's disease.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021
    Article
  14. Review
  15. Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Terence FullertonPfizer Global Product Development, 445 Eastern Point Rd., MS8260-2228, Groton, CT, 06355, USA. terence.fullerton@pfizer.com.
Brendon BinnemanPfizer Internal Medicine Research Unit, Cambridge, MA, USA.
William DavidPfizer Internal Medicine Research Unit, Cambridge, MA, USA.
Marielle DelnomdedieuPfizer Internal Medicine Research Unit, Cambridge, MA, USA.
James KupiecPfizer Global Product Development, 445 Eastern Point Rd., MS8260-2228, Groton, CT, 06355, USA.
Peter LockwoodPfizer Global Product Development, 445 Eastern Point Rd., MS8260-2228, Groton, CT, 06355, USA.
Jessica MancusoPfizer Early Clinical Research, Cambridge, MA, USA.
Jeffrey MiceliPfizer Internal Medicine Research Unit, Cambridge, MA, USA.
Joanne BellPfizer Global Product Development, 445 Eastern Point Rd., MS8260-2228, Groton, CT, 06355, USA.
Pfizer (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSymptomatic benefits have been reported for 5-HT

methodsThis was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial evaluating the efficacy and safety of SAM-760 30 mg once daily (QD) for 12 weeks in subjects with AD on a stable regimen of donepezil 5 to 10 mg QD. The study included an interim analysis with stopping rules for futility or efficacy after 180 subjects completed the week 12 visit. Up to 342 subjects with AD (Mini-Mental State Examination (MMSE) score 10-24) and neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI) total score ≥ 10) were to be enrolled if the study continued after the interim analysis. After a 4-week, single-blind, placebo run-in period, subjects entered the 12-week double-blind period and were randomized to either SAM-760 or placebo. The primary and key secondary efficacy endpoints were the change from baseline in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog13) and NPI total scores. Mixed models for repeated measures were used to analyze the data.

resultsAt the interim analysis, when 186 subjects had been randomized and 163 had completed the week 12 visit, the study met futility criteria and was stopped. The mean week 12 treatment difference was 0.70 points (P = 0.43) for ADAS-cog13 and 2.19 points (P = 0.20) for NPI score, both of which were numerically in favor of placebo. Other secondary endpoints did not demonstrate any significant benefit for SAM-760. In total, 46.2% of SAM-760 subjects reported adverse events (AE) versus 44.7% for placebo, and there were 5 (5.5%) serious AEs in the SAM-760 group versus 3 (3.2%) for placebo. There were two deaths, one prior to randomization and one in the SAM-760 group (due to a traffic accident during washout of active treatment).

conclusionsSAM-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-HT

trial registrationClinicaltrials.gov, NCT01712074 . Registered 19 October 2012.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseBayes TheoremCholinesterase InhibitorsCognition DisordersDonepezilDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansImidazolesMalePiperazinesProtein Kinase InhibitorsPsychiatric Status Rating ScalesCholinesterase InhibitorsDonepezilImidazolesPiperazinesProtein Kinase InhibitorsSAM-760Serotonin Antagonists5-HTAlzheimer’s DiseaseSerotonin

Identifiers

PMID29622037
PMCPMC5887246
OpenAlexW2800293813

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.