Sodium-channel blocker LTG-001 reduced pain after surgery in a 343-patient phase 2b trial

What happened

NaV1.8 is a voltage-gated sodium channel found in peripheral nerves that plays a critical part in pain signalling. This double-blind, randomised, placebo-controlled phase 2b trial tested LTG-001, a selective NaV1.8 inhibitor taken by mouth, in 343 patients with moderate-to-severe pain after abdominoplasty. Patients received a low dose, a high dose, hydrocodone–acetaminophen or placebo for 48 hours.

The primary end point was a time-weighted sum of pain-intensity differences over 48 hours (SPID48), where higher is better. Least-squares means were 161.05 for the low dose, 185.30 for the high dose, 164.08 for hydrocodone–acetaminophen and 123.22 for placebo. Both doses beat placebo (differences of 37.82, P = 0.003, and 62.08, P < 0.001). Patients on the high dose used less opioid rescue medication than those on placebo (11.00 versus 18.35 morphine milligram equivalents) and more of them needed none (52% versus 22%).

Why it matters

Earlier trials of NaV1.8 inhibitors had shown reduced postoperative pain. Another selective inhibitor showing an effect in a controlled trial, with the high dose numerically ahead of an opioid combination, strengthens the case that blocking this peripheral-nerve channel is a workable approach to acute pain.

Caveats

The trial was funded by Latigo Biotherapeutics, the developer of LTG-001, and the first and last authors are affiliated with the company. It is a phase 2b study in one type of surgery, with 48 hours of treatment. The comparison with hydrocodone–acetaminophen was not reported as a statistical test in the abstract. The high dose was associated with more pyrexia (7% versus 2%) and presyncope (6% versus 1%) than placebo. This entry is based on the abstract.