Phase 2b Trial of a NaV1.8 Inhibitor for Acute Pain.

Previous trials of NaV1.8 inhibitors have shown effectiveness in reducing postoperative pain.

先前的Nav1.8抑制剂试验已经显示出在减轻术后疼痛方面的有效性。

Methods

We conducted a phase 2b, double-blind, randomized, placebo-controlledtrial to evaluate LTG-001, a selective Nav1.8 inhibitor, in patients with moderate-to-severe pain after abdominoplasty.

我们开展了一项2b期、双盲、随机、安慰剂对照试验，以评估选择性Nav1.8抑制剂LTG-001在 abdominoplasty术后中度至重度疼痛患者中的疗效。

Patients were randomly assigned in a 1:1:1:1 ratio to receive a 300-mg loading dose of LTG-001, followed by 150 mg every 12 hours (low-dose group); a 450-mg loading dose of LTG-001, followed by 300 mg every 12 hours (high-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen) every 6 hours; or placebo every 6 hours.

患者按1:1:1:1的比例随机分配，接受300毫克的LTG-001负荷剂量，随后每12小时150毫克（低剂量组）；接受450毫克的LTG-001负荷剂量，随后每12小时300毫克（高剂量组）；每6小时接受一次盐酸羟考酮-对乙酰氨基酚（5毫克盐酸羟考酮和325毫克对乙酰氨基酚）；或每6小时接受一次安慰剂。

All doses were administered orally over a 48-hour period.

所有剂量在48小时内通过口服给药。

The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour treatment period (SPID48), based on scores on the Numeric Pain Rating Scale (range, 0 to 10, with higher values indicating more severe pain; higher SPID48 values indicate greater pain reduction).

主要终点是基于数字疼痛评分量表（范围，0至10，数值越高表示疼痛越严重；SPID48值越高表示疼痛减轻越多）在48小时治疗期间疼痛强度差的时间加权总和（SPID48）。

Secondary end points included the amount of opioid rescue medication consumed in morphine milligram equivalents (MME) and no receipt of opioid rescue medication.

次要终点包括以吗啡毫克当量(MME)计算的阿片类药物救急用药的消耗量以及未接受阿片类药物救急用药的情况。

Results

A total of 343 patients underwent randomization.

共有343名患者进行了随机分组。

The least-squares mean SPID48 was 161.05 (95% confidence interval[CI], 142.93 to 179.16) in the low-dose group, 185.30 (95% CI, 167.26 to 203.34) in the high-dose group, 164.08 (95% CI, 146.02 to 182.14) in the hydrocodone bitartrate-acetaminophen group, and 123.22 (95% CI, 105.23 to 141.21) in the placebo group.

在低剂量组中，最小二乘法平均SPID48为161.05（95%置信区间[CI]，142.93至179.16），高剂量组为185.30（95% CI，167.26至203.34），盐酸羟考酮-对乙酰氨基酚组为164.08（95% CI，146.02至182.14），安慰剂组为123.22（95% CI，105.23至141.21）。

The least-squares mean difference in the SPID48 between LTG-001 and placebo was significant for each dose (low dose: 37.82 [P = 0.003]; high dose: 62.08 [P<0.001]), and that between hydrocodone bitartrate-acetaminophen and placebo was 40.86.

LTG-001与安慰剂之间的SPID48最小二乘法平均差异在每个剂量组中都是显著的（低剂量：37.82 [P = 0.003]；高剂量：62.08 [P<0.001]），而盐酸羟考酮-对乙酰氨基酚与安慰剂之间的差异为40.86。

High-dose LTG-001, but not low-dose LTG-001, was associated with significantly lower opioid use than placebo (11.00 MME vs. 18.35 MME, P = 0.01), as well as a significantly higher percentage of patients who received no opioid rescue medication (52% vs. 22%, P<0.001).

高剂量LTG-001与安慰剂相比，显著降低了阿片类药物的使用量（11.00 MME vs. 18.35 MME, P = 0.01），并且显著提高了未使用阿片类药物救急治疗的患者比例（52% vs. 22%, P<0.001）。

High-dose LTG-001 was associated with a higher incidenceof pyrexia than placebo (7% vs. 2%) and a higher incidenceof presyncope (6% vs. 1%).

高剂量LTG-001与安慰剂相比，发热的发生率更高（7% vs. 2%），以及晕厥前兆的发生率更高（6% vs. 1%）。

Conclusions

LTG-001 led to significantly greater reductions in pain scores than placebo over the course of 48 hours after abdominoplasty.

在腹部整形术后48小时内，LTG-001相较于安慰剂显著降低了疼痛评分。

(Funded by Latigo Biotherapeutics; LTG-001-010 ClinicalTrials.gov number, NCT07102459.).

该研究由Latigo Biotherapeutics资助；LTG-001-010的ClinicalTrials.gov编号为NCT07102459。