Purpose

Dry eye disease (DED) symptoms can negatively impact quality of life (QoL). AR-15512, a transient receptor potential melastatin 8 (TRPM8) agonist, was evaluated as a potential therapy for DED.

Methods

In a Phase 2b study, patients with DED were randomized 1:1:1 to 0.0014% AR-15512, 0.003% AR-15512, or vehicle twice daily for 12 weeks. Eligibility criteria included DED signs and symptoms of prespecified severity levels. Outcomes assessed were DED signs (Schirmer score ± anesthetic, ocular surface staining, hyperemia), symptoms (Ocular Discomfort [ODS-VAS], Symptoms Assessment iN Dry Eye [SANDE], Eye Dryness-VAS, Ocular Pain-VAS), QoL-VAS, and adverse events. Co-primary endpoints were changes from baseline in ODS-VAS and anesthetized Schirmer score at Day 28.

Results

0.003% AR-15512 (n = 122) was associated with early and sustained improvements in unanesthetized Schirmer score (Days 1 and 14, p < 0.0001), as well as improvements in ocular surface staining (Days 14 and 84, p ≤ 0.0365) and hyperemia (Day 84, p < 0.0215). Statistically significant improvements in symptoms were observed for the 0.003% concentration on SANDE (Days 14, 28, and 84, p ≤ 0.0254), ODS-VAS (Day 84, p = 0.0281), Eye Dryness-VAS (Day 84, p = 0.0302), and multiple QoL measures (Days 14, 28, and 84, p < 0.05). There were no significant differences between active and vehicle groups for the co-primary endpoints. The most common adverse events were burning and stinging upon instillation.

Conclusions

Although predefined co-primary study endpoints were not met, AR-15512 demonstrated statistically significant improvements in DED signs, symptoms, and disease-related QoL.

中文翻译：

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两种浓度的 TRPM8 受体激动剂 AR-15512 治疗干眼症 (COMET-1) 的随机、载体对照、2b 期研究

目的

干眼病 (DED) 症状会对生活质量 (QoL) 产生负面影响。AR-15512 是一种瞬时受体电位 melastatin 8 (TRPM8) 激动剂，被评估为 DED 的潜在疗法。

方法

在 2b 期研究中，DED 患者以 1:1:1 的比例随机分配至 0.0014% AR-15512、0.003% AR-15512 或载体，每天两次，持续 12 周。资格标准包括预先指定的严重程度级别的 DED 体征和症状。评估的结果是 DED 体征（Schirmer 评分±麻醉剂、眼表染色、充血）、症状（眼部不适 [ODS-VAS]、干眼症状评估 [SANDE]、眼干-VAS、眼痛-VAS）、QoL- VAS 和不良事件。共同主要终点是第 28 天 ODS-VAS 和麻醉 Schirmer 评分相对于基线的变化。

结果

0.003% AR-15512 (n = 122) 与未麻醉 Schirmer 评分的早期和持续改善（第 1 天和第 14 天，p < 0.0001）以及眼表染色的改善（第 14 天和第 84 天，p ≤ 0.0365）相关和充血（第 84 天，p < 0.0215）。在 SANDE（第 14、28 和 84 天，p ≤ 0.0254）、ODS-VAS（第 84 天，p = 0.0281）、眼睛干涩-VAS（第 84 天，p = 0.0302) 和多项 QoL 措施（第 14、28 和 84 天，p < 0.05）。对于共同主要终点，活性组和载体组之间没有显着差异。最常见的不良事件是滴注时灼痛和刺痛。

结论

尽管未达到预定义的共同主要研究终点，但 AR-15512 在 DED 体征、症状和疾病相关 QoL 方面表现出统计学上的显着改善。