Evidence map›Paper›PMID 26849844›Full record

Trial reportCNS neuroscience & therapeutics2016

Exploratory Biomarker Study of the Triple Reuptake Inhibitor SEP-432 Compared to the Dual Reuptake Inhibitor Duloxetine in Healthy Normal Subjects.

John J Sramek, Larry W Hardy, Peter Bieck, Cynthia Zamora, Mark Versavel, Jahnavi Kharidia, Todd Grinnell, Yu-Luan Chen, Michael Sullivan, Hong Ding and 1 more

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in CNS neuroscience & therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.2field-weighted citation impact, top 41% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. 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

11 authors at 2 institutions in 2 countries.

John J SramekWorldwide Clinical Trials, Beverly Hills, CA, USA.
Larry W HardySunovion Pharmaceuticals, Marlborough, MA, USA.
Peter BieckWorldwide Clinical Trials, Beverly Hills, CA, USA.
Cynthia ZamoraWorldwide Clinical Trials, Drug Development Solutions, San Antonio and Austin, TX, USA.
Mark VersavelSunovion Pharmaceuticals, Marlborough, MA, USA.
Jahnavi KharidiaSunovion Pharmaceuticals, Marlborough, MA, USA.
Todd GrinnellSunovion Pharmaceuticals, Marlborough, MA, USA.
Yu-Luan ChenSunovion Pharmaceuticals, Marlborough, MA, USA.
Michael SullivanWorldwide Clinical Trials, Drug Development Solutions, San Antonio and Austin, TX, USA.
Hong DingWorldwide Clinical Trials, Beverly Hills, CA, USA.
Neal R CutlerWorldwide Clinical Trials, Beverly Hills, CA, USA.
Worldwide Clinical Trials (United States) · USSunovion (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSEP-432 is a triple monoamine reuptake inhibitor of norepinephrine (NE), serotonin (5-HT), and dopamine (DA), based on in vitro binding studies. We sought evidence that SEP-432 engages these monoamine systems by measuring concentrations of monoamines and/or their main metabolites in cerebrospinal fluid (CSF) and plasma and comparing results to duloxetine, a dual reuptake inhibitor of NE and 5-HT.

methodsEighteen healthy normal subjects received either SEP-432 (300 mg/day), duloxetine (60 mg/day), or placebo for 14 days in-clinic (double blind) with CSF and plasma collections at baseline (single lumbar puncture) and Day 14 (24-h CSF and plasma collection). Concentrations of monoamines and their metabolites, as well as pharmacokinetic concentrations of SEP-432 and metabolite, were quantified by liquid chromatography-tandem mass spectrometry.

resultsCompared to placebo in the Day 14 area under the curve 24-h (AUC0-24 h ) analysis, SEP-432 significantly (P < 0.05) decreased the NE metabolite dihydroxyphenylglycol (DHPG) in CSF and plasma, decreased 5-HT in plasma, and did not affect DA metabolites, while duloxetine had significant effects on DHPG and 5-HT. Time-matched baseline to Day 14 biomarker comparisons confirmed these findings.

conclusionCSF monoamine biomarkers confirmed central NET activity for SEP-432 and duloxetine's dual reuptake inhibition.

Indexed as

AdultBiogenic MonoaminesBiomarkers, PharmacologicalChromatography, High Pressure LiquidCyclohexanolsDimethylaminesDose-Response Relationship, DrugDouble-Blind MethodDuloxetine HydrochlorideElectrocardiographyFemaleHealthy VolunteersHumansMaleMethoxyhydroxyphenylglycolMiddle Aged3,4-dihydroxyphenylglycol4-(3,4-dichlorophenyl)-4-((dimethylamino)methyl)-1-methylcyclohexanolBiogenic MonoaminesBiomarkers, PharmacologicalCyclohexanolsDimethylaminesDuloxetine HydrochlorideMethoxyhydroxyphenylglycolNeurotransmitter AgentsNeurotransmitter Uptake InhibitorsBiomarkersCerebrospinal fluidDuloxetineMonoamine reuptake inhibitorSEP-432

Identifiers

PMID26849844
PMCPMC6492792
OpenAlexW2278805889

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.