• Hemme J Hijma, Pieter S Siebenga, Marieke L de Kam, and GroeneveldGeert JanGJCentre for Human Drug Research, Leiden, The Netherlands.Leiden University Medical Center, Leiden, The Netherlands..
• Centre for Human Drug Research, Leiden, The Netherlands.
• Pain Med. 2021 Aug 6; 22 (8): 1814-1826.

ObjectiveTo evaluate the analgesic potential, safety, tolerability, and pharmacokinetics of VX-150, a pro-drug of a highly selective NaV1.8 inhibitor, in healthy subjects.DesignThis was a randomized, double-blind, placebo-controlled, crossover study in healthy subjects.SubjectsTwenty healthy male subjects with an age of 18-55 years, inclusive, were enrolled. Eligibility was based on general fitness, absence of current or previous medical conditions that could compromise subject safety, and a training assessment of pain tolerance across pain tests to exclude highly tolerant individuals whose tolerance could compromise the ability to detect analgesic responses. All dosed subjects completed the study.MethodsSubjects were randomized 1:1 to one of two sequences receiving a single VX-150 dose and subsequently placebo, or vice versa, with at least 7 days between dosing. A battery of pain tests (pressure, electrical stair, [capsaicin-induced] heat, and cold pressor) was administered before dosing and repetitively up to 10 h after dosing, with blood sampling up to 24 h after dosing. Safety was monitored throughout the study. Data were analyzed with a repeated-measures mixed-effects model.ResultsVX-150 induced analgesia in a variety of evoked pain tests, without affecting subject safety. Significant effects were reported for the cold pressor and heat pain thresholds. Maximum median concentration for the active moiety was 4.30 µg/mL at 4 h after dosing.ConclusionResults of this proof-of-mechanism study are supportive of the potential of VX-150, a highly selective NaV1.8 channel inhibitor, to treat various pain indications.© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.

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