Study of the analgesic effect of lanepitant in patients with osteoarthritis pain

Objective: Lanepitant selectively blocks substance P binding to the neuroki nin-l receptor, preventing neurogenic inflammation and pain transmission. S ubstance P is present in synovial fluid and in excess in cerebral spinal fl uid. We investigated the effect of lanepitant on pain caused by osteoarthri tis to evaluate the role of neurokinin-1 blockade. Methods: Outpatients (n = 214) with moderate to severe lower-limb osteoarth ritis pain were treated for 3 weeks in a parallel, randomized double-blind study with initial doses of 20, 60, 200, or 600 mg lanepitant, 375 mg napro xen, or placebo, followed by 10, 30, 100, or 300 mg lanepitant twice a day, 375 mg naproxen twice a day, or placebo twice a day in the multiple-dose p eriod. Pain intensity, pain relief, patient global impression, and adjuncti ve analgesic use were compared across treatments. Safety was evaluated with adverse events, vital signs, and laboratory assessments. Results: There was no statistically significant difference in efficacy or s afety across treatments for the initial dose assessment. After 1 week of th erapy naproxen was statistically significantly (P < .05) better than placeb o and lanepitant in reducing average pain. During the second and third week s of therapy patients receiving naproxen continued to have statistically si gnificantly (P < .05) less pain than those receiving placebo or lanepitant despite using significantly less adjunctive analgesic medication. There wer e no statistically significant differences in rates of discontinuation acro ss treatments. Lanepitant treatment was associated with diarrhea, whereas n aproxen treatment was associated with gastric discomfort. There were no cli nically relevant changes in vital signs or laboratory analytes for any of t he treatments. Conclusion: Lanepitant was ineffective in relieving osteoarthritis pain, po ssibly because neurokinin-l binding of substance P does not play a signific ant role in osteoarthritis pain or because lanepitant fails to adequately p enetrate the blood-brain barrier to affect central pain perception.