Evidence map›Paper›PMID 30915991›Full record

Trial reportBritish journal of anaesthesia2019

Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABA

Guido van Amerongen, Pieter S Siebenga, Rachel Gurrell, Pinky Dua, Mark Whitlock, Donal Gorman, Pieter Okkerse, Justin L Hay, Richard P Butt, Geert Jan Groeneveld

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in British journal of anaesthesia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02238717 (A Double Blind, Double Dummy, Randomized, Placebo-controlled, 4 Period Cross-over Study To Examine The Effect Of Pf-06372865 On Evoked Pain Endpoints In Healthy Volunteers Using Pregabalin As A Positive Control), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.3field-weighted citation impact, top 11% 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.

NCT02238717 phase1completednot on this map

A Double Blind, Double Dummy, Randomized, Placebo-controlled, 4 Period Cross-over Study To Examine The Effect Of Pf-06372865 On Evoked Pain Endpoints In Healthy Volunteers Using Pregabalin As A Positive Control

TypeinterventionalSponsorPfizerRan2014 to 2014Enrolled20ConditionsHealthyArmsPF-06372865 (65mg), PF-06372865 (15mg), Pregabalin, Placebo
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 28 citations in OpenAlex.

  1. Antinociceptive Effects ofThe Journal of pharmacology and experimental therapeutics · 2024
    Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. The efficacy of γ-aminobutyric acid type A receptor (GABAToxicology and applied pharmacology · 2021
    Article
  7. 5-International journal of molecular sciences · 2021
    Article
  8. Review
  9. Progress in pain medicine: where are we now?British journal of anaesthesia · 2019
    Article
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

10 authors at 2 institutions in 2 countries.

Guido van AmerongenCentre for Human Drug Research (CHDR), Leiden, the Netherlands. Electronic address: GvAmerongen@chdr.nl.
Pieter S SiebengaCentre for Human Drug Research (CHDR), Leiden, the Netherlands.
Rachel GurrellEarly Clinical Development, Pfizer WRD, Cambridge, UK.
Pinky DuaEarly Clinical Development, Pfizer WRD, Cambridge, UK.
Mark WhitlockEarly Clinical Development, Pfizer WRD, Cambridge, UK.
Donal GormanEarly Clinical Development, Pfizer WRD, Cambridge, UK.
Pieter OkkerseCentre for Human Drug Research (CHDR), Leiden, the Netherlands.
Justin L HayCentre for Human Drug Research (CHDR), Leiden, the Netherlands.
Richard P ButtEarly Clinical Development, Pfizer WRD, Cambridge, UK.
Geert Jan GroeneveldCentre for Human Drug Research (CHDR), Leiden, the Netherlands.
Centre for Human Drug Research · NLPfizer (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThis study investigated the analgesic effects of two doses (15 and 65 mg) of PF-06372865, a novel α2/α3/α5 gamma-aminobutyric acid A (GABA

methodsWe performed a randomised placebo-controlled crossover study (NCT02238717) in 20 healthy subjects, using a battery of pain tasks (electrical, pressure, heat, cold and inflammatory pain, including a paradigm of conditioned pain modulation). Pharmacodynamic measurements were performed at baseline and up to 10 h after dose.

resultsA dose of 15 mg PF-06372865 increased pain tolerance thresholds (PTTs) for pressure pain at a ratio of 1.11 (90% confidence interval [CI]: 1.02, 1.22) compared with placebo. A dose of 65 mg PF-06372865 led to an increase in PTT for the cold pressor at a ratio of 1.17 (90% CI: 1.03, 1.32), and pressure pain task: 1.11 (90% CI: 1.01, 1.21). Pregabalin showed an increase in PTT for pressure pain at a ratio of 1.15 (95% CI: 1.06, 1.26) and cold pressor task: 1.31 (90% CI: 1.16, 1.48).

conclusionWe conclude that PF-06372865 has analgesic potential at doses that do not induce significant sedation or other intolerable adverse events limiting its clinical use. In addition, the present study established the potential role for this battery of pain tasks as a tool in the development of analgesics with a novel mechanism of action, for the treatment of various pain states including neuropathic pain and to establish proof-of-concept. CLINICAL TRIALS REGISTRATION: NCT0223871.

Indexed as

AdultAnalgesicsCross-Over StudiesDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansImidazolesMalePainPyridazinesAnalgesicsImidazolesPF-06372865PyridazinesanalgesiaanalgesicsGABA-A receptorneuropathic painpainpositive allosteric modulator

Identifiers

PMID30915991
PMCPMC6676245
OpenAlexW2911232074

What OpenQuestion holds

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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.