Oral LPCN 1148 improves sarcopenia and hepatic encephalopathy in male patients with cirrhosis: A randomized, placebo-controlled phase 2 trial.

Androgen receptor agonists, androgen receptor agonists, can address these conditions through multimodal mechanisms of action; however, their safety and efficacy in patients with cirrhosis have not been well established.

雄激素受体激动剂可以通过多种作用机制解决这些问题；然而，它们在肝硬化患者中的安全性和有效性尚未得到充分确立。

approach_and_results

In this multicenter, double-blind, phase 2 trial, men with sarcopenia and cirrhosis awaiting liver transplant were randomized 1:1 to receive either oral Androgen Receptor Agonist LPCN 1148 or placebo for 24 weeks (NCT04874350).

在这项多中心、双盲、二期临床试验中，等待肝移植的肌肉减少症和肝硬化男性患者按1:1的比例随机接受口服雄激素受体激动剂LPCN 1148或安慰剂治疗，为期24周（NCT04874350）。

The primary end point was the change from baseline to 24 weeks in skeletal muscle index measured by a CT scan of the L3 region, analyzed with a prespecified modified intent-to-treat population.

主要终点是从基线到24周通过L3区域的CT扫描测量的骨骼肌指数的变化，分析采用预先设定的修改意向治疗人群。

The secondary end point was the number of overt HE events.

次要终点是明显肝性脑病（HE）事件的数量。

Twenty-nine participants (mean age=59 y, MELD=17) received at least 1 dose of LPCN 1148 (n=15) or placebo (n=14).

29名参与者（平均年龄59岁，MELD评分为17）至少接受了1剂LPCN 1148（n=15）或安慰剂（n=14）。

Baseline characteristics were similar between groups.

两组基线特征相似。

Primary end point analysis demonstrated an increase in L3-skeletal muscle index measured by a CT scan of the L3 region in the LPCN 1148 group (n=15) compared to placebo (n=10), with a mean group difference of 4.4 cm 2 /m 2 (95% CI: 1.3-7.4 cm 2 /m 2 , p =0.007).

主要终点分析显示，在L3区域通过CT扫描测量的L3骨骼肌指数在LPCN 1148组（n=15）中比安慰剂组（n=10）有所增加，两组平均差异为4.4 cm 2 /m 2（95%置信区间：1.3-7.4 cm 2 /m 2，p=0.007）。

Participants in LPCN 1148 experienced fewer episodes of overt HE (Common Terminology Criteria for Adverse Events grade ≥2; p =0.02) than placebo.

LPCN 1148的参与者经历的明显肝性脑病发作（不良事件通用术语标准等级≥2）的次数少于安慰剂组（p=0.02）。

The number and severity of treatment-emergent adverse events were similar between arms.

两组间治疗相关不良事件的数量和严重程度相似。

Conclusions

LPCN 1148 treatment improved sarcopenia and reduced the number of overt HE episodes in men with cirrhosis and sarcopenia awaiting liver transplant.

LPCN 1148治疗改善了肝硬化和肌肉消瘦男性患者的肌肉消瘦状况，并减少了明显肝性脑病发作的次数，这些患者正在等待肝脏移植。

These findings support additional research on the efficacy of LPCN 1148 in treating sarcopenia and preventing HE recurrence.

这些发现支持了对LPCN 1148在治疗肌肉消瘦和预防肝性脑病复发方面的疗效进行进一步研究。