Trial reportBritish journal of clinical pharmacology2018
Demonstration of an anti-hyperalgesic effect of a novel pan-Trk inhibitor PF-06273340 in a battery of human evoked pain models.
Trial report in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02260947 (A Double Blind, Double Dummy, Randomized, Placebocontrolled, 5 Period Cross-over Study To Examine The Effect of Pf-06273340 On Evoked Pain Endpoints In Healthy Volunteers Using Pregabalin And Ibuprofen As Positive Controls), which is not on this map. Cited by 13 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
A Double Blind, Double Dummy, Randomized, Placebocontrolled, 5 Period Cross-over Study To Examine The Effect of Pf-06273340 On Evoked Pain Endpoints In Healthy Volunteers Using Pregabalin And Ibuprofen As Positive Controls
Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Pooled it
- Methodology and applicability of the human contact burn injury model: A systematic review.PloS one · 2021Pooled it
- Randomized, placebo-controlled study on the effects of intravenous GSK3858279 (anti-CCL17) on a battery of evoked pain tests in healthy participants.Clinical and translational science · 2024Trial
- First-in-human trial to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of STR-324, a dual enkephalinase inhibitor for pain management.British journal of clinical pharmacology · 2022Trial
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults.Pain medicine (Malden, Mass.) · 2021Trial
- Lack of Detection of the Analgesic Properties of PF-05089771, a Selective NaClinical and translational science · 2020Trial
- Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABABritish journal of anaesthesia · 2019Trial
- Demonstration of an anti-hyperalgesic effect of a novel pan-Trk inhibitor PF-06273340 in a battery of human evoked pain models.British journal of clinical pharmacology · 2018Trial
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
- Mechanism-based nonopioid analgesic targets.The Journal of clinical investigation · 2025Review
- Does In Vitro Potency Predict Clinically Efficacious Concentrations?Clinical pharmacology and therapeutics · 2020Article
- The ultraviolet B inflammation model: Postinflammatory hyperpigmentation and validation of a reduced UVB exposure paradigm for inducing hyperalgesia in healthy subjects.European journal of pain (London, England) · 2019Article
- Quantitative Systems Pharmacology and Empirical Models: Friends or Foes?CPT: pharmacometrics & systems pharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimInhibitors of nerve growth factor (NGF) reduce pain in several chronic pain indications. NGF signals through tyrosine kinase receptors of the tropomyosin-related kinase (Trk) family and the unrelated p75 receptor. PF-06273340 is a small molecule inhibitor of Trks A, B and C that reduces pain in nonclinical models, and the present study aimed to investigate the pharmacodynamics of this first-in-class molecule in humans.
methodsA randomized, double-blind, single-dose, placebo- and active-controlled five-period crossover study was conducted in healthy human subjects (NCT02260947). Subjects received five treatments: PF-06273340 50 mg, PF-06273340 400 mg, pregabalin 300 mg, ibuprofen 600 mg and placebo. The five primary endpoints were the pain detection threshold for the thermal pain tests and the pain tolerance threshold for the cold pressor, electrical stair and pressure pain tests. The trial had predefined decision rules based on 95% confidence that the PF-06273340 effect was better than that of placebo.
resultsTwenty subjects entered the study, with 18 completing all five periods. The high dose of PF-06273340 met the decision rules on the ultraviolet (UV) B skin thermal pain endpoint [least squares (LS) mean vs. placebo: 1.13, 95% confidence interval: 0.64-1.61], but not on the other four primary endpoints. The low dose did not meet the decision criteria for any of the five primary endpoints. Pregabalin (cold pressor and electrical stair tests) and ibuprofen (UVB thermal pain) showed significant analgesic effects on expected endpoints.
conclusionsThe study demonstrated, for the first time, the translation of nonclinical effects into man in an inflammatory pain analgesic pharmacodynamic endpoint using a pan-Trk inhibitor.
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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.