An investigational oral selective Nav1.8 inhibitor called LTG-001 may be associated with greater reductions in postoperative pain compared with placebo in patients undergoing abdominoplasty in a recent study.
In a phase 2b, double-blind, randomized, placebo-controlled trial at four US centers involving 343 participants aged 18 to 65 years undergoing elective lower abdominoplasty with rectus plication, researchers randomly assigned the patients 1:1:1:1 to receive low-dose LTG-001, high-dose LTG-001, hydrocodone bitartrate–acetaminophen, or placebo for 48 hours. The patients were eligible if they reported moderate or severe pain at rest within 4 hours following surgery and had a Numeric Pain Rating Scale score of at least 5. Patients with chronic pain, current or long-term opioid use, depression, anxiety, or other psychiatric disorders were excluded if they had not been clinically stable for at least 90 days prior to surgery. The primary endpoint was the time-weighted sum of the pain-intensity difference over 48 hours (SPID48). The researchers noted that a minimum clinically important difference for SPID48 has not been established in acute pain.
Overall, 97% of the patients completed the treatment regimen, and baseline characteristics were similar across the groups. Least-squares mean SPID48 values were 161 in the low-dose LTG-001 group, 185 in the high-dose group, 164 in the hydrocodone bitartrate–acetaminophen group, and 123 in the placebo group. Compared with placebo, both LTG-001 doses were associated with statistically significant improvements in SPID48. Sensitivity analyses were generally consistent with the primary analysis. In the treatment-policy analysis, which did not impute Numeric Pain Rating Scale scores following opioid rescue treatment, the estimated treatment effects were smaller between the groups.
High-dose LTG-001, but not low-dose LTG-001, was associated with lower rescue opioid use compared with placebo. Least-squares mean rescue opioid consumption was 11 morphine milligram equivalents in the high-dose group compared with 18 in the placebo group. Compared with those receiving placebo, 52% vs. 22% of the patients receiving high-dose LTG-001 required no rescue opioid medication. The median time to a clinically meaningful reduction of at least 2 points on the Numeric Pain Rating Scale was 52 minutes with high-dose LTG-001, 60 minutes with low-dose LTG-001, 83 minutes with hydrocodone bitartrate–acetaminophen, and 88 minutes with placebo.
At least one adverse event was reported in 50% of the patients receiving high-dose LTG-001 compared with 62% of those receiving low-dose LTG-001, 63% receiving hydrocodone bitartrate–acetaminophen, and 65% receiving placebo. Most adverse events were mild or moderate. Nausea, headache, and dizziness were the most common adverse events. Pyrexia (7% vs. 2%) and presyncope (6% vs. 1%) occurred more frequently with high-dose LTG-001 compared with placebo. Serious adverse events occurred in 1 patient in each treatment group, none were considered treatment related, and no mortalities were reported. No clinically meaningful changes were observed in laboratory results, echocardiograms, vital signs, or physical examination findings. The trial did not include formal comparisons between LTG-001 and hydrocodone bitartrate–acetaminophen, so the findings do not allow conclusions about their relative efficacy.
The researchers noted that the trial evaluated LTG-001 as monotherapy rather than as part of multimodal pain management. They also noted that most participants were female undergoing abdominoplasty and that those with chronic pain conditions or previous opioid use were excluded, which may limit the applicability of the findings to other patient populations.
The trial was funded by Latigo Biotherapeutics. Disclosure forms are available with the article.
