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.

OBJECTIVE

To evaluate the analgesic potential, safety, tolerability, and pharmacokinetics of VX-150, a pro-drug of a highly selective NaV1.8 inhibitor, in healthy subjects.

DESIGN

This was a randomized, double-blind, placebo-controlled, crossover study in healthy subjects.

SUBJECTS

Twenty 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.

METHODS

Subjects 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.

RESULTS

VX-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.

CONCLUSION

Results 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.