Relieving postoperative pain using a novel NaV1.8 voltage-gated sodium channel inhibitor
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Reviewed by Nhi Phuong Quynh Le, B.A
Translated by Dat Tien Nguyen, B.A, ScM. |
Posted on September 15th, 2023
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NaV1.8 voltage-gated sodium channel is responsible for transmitting nociceptive signals in the peripheral nervous system. Previous studies have shown that VX-548 can selectively inhibit the NaV1.8 channel in vitro and reduce acute pain in vivo. Thus, researchers conducted a study to examine the effectiveness and safety of using oral VX-548 in patients who are experiencing postoperative acute pain.
The two phase 2 trials included 577 participants who were experiencing acute pain after abdominoplasty and bunionectomy. In the abdominoplasty trial, study participants were randomly assigned to receive one of the following over a 48-hour period: a 100-mg oral of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg of VX-548, followed by a 30-mg maintenance dose every 12 hours (the moderate-dose group); 5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours (the standard therapy group); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; moderate-dose VX-548; low-dose VX-548 (a 20-mg dose, followed by a 10-mg maintenance dose every 12 hours); the standard therapy group; or oral placebo every 6 hours. Researchers used the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48) the Numeric Pain Rating Scale (range from 0 to 10) to assess the patient’s pain level. Researchers found that the mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8% in those who had an abdominoplasty performed and 36.8% in those who had a bunionectomy performed. Compared with placebo, VX-548 at the highest dose, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. Most of the adverse events reported by the participants in both trials were mild to moderate. In both trials, the safety profile was similar between participants who were given the low doses of VX-548 and those who were given placebo. Those who were given VX-548 experienced a higher frequency of headache and constipation.
The two phase 2 trials included 577 participants who were experiencing acute pain after abdominoplasty and bunionectomy. In the abdominoplasty trial, study participants were randomly assigned to receive one of the following over a 48-hour period: a 100-mg oral of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg of VX-548, followed by a 30-mg maintenance dose every 12 hours (the moderate-dose group); 5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours (the standard therapy group); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; moderate-dose VX-548; low-dose VX-548 (a 20-mg dose, followed by a 10-mg maintenance dose every 12 hours); the standard therapy group; or oral placebo every 6 hours. Researchers used the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48) the Numeric Pain Rating Scale (range from 0 to 10) to assess the patient’s pain level. Researchers found that the mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8% in those who had an abdominoplasty performed and 36.8% in those who had a bunionectomy performed. Compared with placebo, VX-548 at the highest dose, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. Most of the adverse events reported by the participants in both trials were mild to moderate. In both trials, the safety profile was similar between participants who were given the low doses of VX-548 and those who were given placebo. Those who were given VX-548 experienced a higher frequency of headache and constipation.