Aims

Diabetic gastroparesis may be associated with impaired nitric oxide metabolism and reduced tetrahydrobiopterin (BH₄) synthesis. Oral treatment with CNSA-001 (sepiapterin, currently known as PTC923) increased BH₄ levels in humans in a previous study. This Phase 2 study evaluated CNSA-001 in women with diabetic gastroparesis.

Methods

Non-pregnant diabetic women with moderate/severe symptomatic gastroparesis, delayed gastric emptying, and impaired gastric accommodation (nutrient satiety testing) were randomized to 10 mg/kg BID CNSA-001 or matching placebo for 14 days. The primary endpoint was change in gastric accommodation (maximal tolerated liquid meal volume) at 14- and 28-days' follow-up.

Results

Gastric accommodation improved in CNSA-001-treated vs. placebo-treated subjects at 28 days (least squares mean [LSM] difference: 98 [95% CI 36 to 161], p = 0.0042). Subjects' ratings of bloating, fullness, nausea, and pain were lower vs. baseline in the CNSA-001 group at 14 and 28 days, though these improvements were not observed consistently in placebo-treated subjects. There were no significant group differences in upper gastrointestinal symptom scores, and in gastric emptying breath test parameters. CNSA-001 was well tolerated, with no withdrawals for adverse events.

Conclusions

CNSA-001 improved gastric accommodation in women with diabetic gastroparesis. Further evaluation of CNSA-001 in gastroparesis is warranted; ClinicalTrials.gov number, NCT03712124.

中文翻译：

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口服 CNSA-001（sepipterin，PTC923）对糖尿病性胃轻瘫女性胃调节的影响：一项随机、安慰剂对照、2 期试验

目标

糖尿病性胃轻瘫可能与一氧化氮代谢受损和四氢生物蝶呤 (BH ₄ ) 合成减少有关。在之前的一项研究中，使用 CNSA-001（sepiaterin，目前称为 PTC923）进行口服治疗会增加人体 BH ₄水平。这项 2 期研究评估了 CNSA-001 在患有糖尿病性胃轻瘫的女性中的作用。

方法

患有中度/重度症状性胃轻瘫、胃排空延迟和胃调节功能受损（营养饱腹感测试）的非妊娠糖尿病女性随机接受 10  mg/kg BID CNSA-001 或匹配安慰剂治疗 14 天。主要终点是在 14 天和 28 天的随访中胃适应能力（最大耐受液体膳食量）的变化。

结果

在 28 天时，接受 CNSA-001 治疗的受试者与接受安慰剂治疗的受试者相比，胃调节得到改善 （最小二乘平均 [LSM] 差异：98 [95% CI 36 至 161]，p  =  0.0042）。在第 14 天和第 28 天，CNSA-001 组受试者的腹胀、饱胀、恶心和疼痛评分低于基线 ，尽管在安慰剂治疗的受试者中并未始终观察到这些改善。上消化道症状评分和胃排空呼气试验参数无显着组间差异。CNSA-001 耐受性良好，没有因不良事件而退出。

结论

CNSA-001 改善了糖尿病性胃轻瘫女性的胃适应能力。有必要进一步评估 CNSA-001 在胃轻瘫中的作用；ClinicalTrials.gov 编号，NCT03712124。