HealthDay News — High-dose VX-548, an oral, highly selective inhibitor of the Nav1.8 voltage-gated sodium channel, reduces acute pain over 48 hours after abdominoplasty and bunionectomy, according to a study published in the Aug. 3 issue of the New England Journal of Medicine.
Jim Jones, M.D., Pharm.D., from Vertex Pharmaceuticals in Boston, and colleagues conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, 303 patients were randomly assigned to receive a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every six hours); or oral placebo every six hours in a 1:1:1:1 ratio. In the bunionectomy trial, 274 participants were randomly assigned to receive oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen; or oral placebo every six hours in a 2:2:1:2:2 ratio.
The researchers found that in the time-weighted sum of the pain-intensity difference during the 48-hour period, the least-squares mean difference between the high-dose VX-548 and placebo groups was 37.8 and 36.8 after abdominoplasty and bunionectomy, respectively. In both trials, results were similar for those receiving lower doses of VX-548 and placebo. Common adverse events with VX-548 were headache and constipation.
“In two phase 2 clinical trials of postoperative pain, as compared with placebo, the highest dose, but not lower doses, of VX-548 reduced pain over a 48-hour period,” the authors write.
Several authors disclosed ties to pharmaceutical companies, including Vertex Pharmaceuticals, the developer of VX-548.