Purpose

To evaluate the efficacy and safety of OC-01 (varenicline solution) nasal spray for treatment of patients with dry eye disease.

Design

Randomized, multicenter, double-masked, vehicle-controlled, phase 3 study.

Participants

Adults 22 years of age or older with a diagnosis of dry eye disease, artificial tear use, Ocular Surface Disease Index score of 23 or more, and Schirmer test score (STS) of 10 mm or less. Eligibility was not restricted by eye dryness score (EDS).

Methods

Patients (N = 758) were randomized in a 1:1:1 ratio to twice-daily treatment with 50-μl intranasal spray in each nostril of OC-01 0.03 mg (n = 260), OC-01 0.06 mg (n = 246), or vehicle (control; n = 252) for 4 weeks (ClinicalTrials.gov identifier, NCT04036292).

Main Outcome Measures

The primary efficacy end point was the percentage of patients achieving a 10-mm improvement or more in STS at week 4. Secondary end points included change from baseline to week 4 in STS and EDS in a controlled adverse environment (CAE) chamber and in the clinic. Treatment-emergent adverse events (TEAEs) were assessed.

Results

A statistically significantly greater percentage of patients achieved the primary end point in both OC-01 treatment groups compared with the vehicle group (OC-01 0.03 mg, 47.3%; OC-01 0.06 mg, 49.2%; vehicle, 27.8%; P < 0.0001 for both doses). Change from baseline in STS at week 4 was statistically significantly greater for patients receiving OC-01 than vehicle (P < 0.0001 for both doses). Eye dryness score assessed at week 4 improved with OC-01 treatment compared with vehicle, although the difference was not significant for EDS measured in the CAE chamber and showed (nominal) significance in the clinic. Overall, 86.5% of patients (654/756) reported at least 1 TEAE during the treatment period; most were mild, nonocular (sneezing, cough, throat irritation, and instillation site irritation) and were reported by fewer patients in the vehicle group than in the OC-01 treatment groups (OC-01 0.03 mg, 97.3%; OC-01 0.06 mg, 99.2%; vehicle, 57%).

Conclusions

OC-01 nasal spray was well tolerated and showed a clinically meaningful effect on signs and symptoms of dry eye disease.

中文翻译：

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OC-01（伐尼克兰溶液）鼻喷雾剂对干眼症体征和症状的疗效和安全性

目的

评价OC-01（伐尼克兰溶液）鼻喷雾剂治疗干眼症患者的疗效和安全性。

设计

随机、多中心、双盲、车辆控制的 3 期研究。

参与者

诊断为干眼症、使用人工泪液、眼表疾病指数评分为 23 或更高、Schirmer 测试评分 (STS) 为 10 毫米或更低的 22 岁或以上的成年人。资格不受眼干评分（EDS）的限制。

方法

患者 (N = 758) 以 1:1:1 的比例随机分组，每天两次使用 50 μl 的 OC-01 0.03 mg (n = 260)、OC-01 0.06 mg (n = 246），或车辆（对照；n = 252）4 周（ClinicalTrials.gov 标识符，NCT04036292）。

主要观察指标

主要疗效终点是第 4 周 STS 改善 10 mm 或更多的患者百分比。次要终点包括在受控不利环境 (CAE) 室和在 STS 和 EDS 中从基线到第 4 周的变化。诊所。评估了治疗中出现的不良事件（TEAE）。

结果

与载体组相比，两个 OC-01 治疗组中达到主要终点的患者比例在统计学上显着增加（OC-01 0.03 mg，47.3%；OC-01 0.06 mg，49.2%；载体，27.8%；P <两种剂量均为 0.0001）。接受 OC-01 的患者在第 4 周时 STS 从基线的变化在统计学上显着大于载体（P< 0.0001 两种剂量）。OC-01 治疗与载体相比，在第 4 周评估的眼干评分有所改善，尽管在 CAE 室中测量的 EDS 差异不显着，并且在临床中显示（标称）显着性。总体而言，86.5% 的患者 (654/756) 在治疗期间报告了至少 1 次 TEAE；大多数是轻微的、非眼部的（打喷嚏、咳嗽、喉咙刺激和滴注部位刺激），并且载体组报告的患者少于 OC-01 治疗组（OC-01 0.03 mg，97.3%；OC-01 0.06毫克，99.2%；载体，57%）。

结论

OC-01 鼻喷雾剂耐受性良好，对干眼症的体征和症状具有临床意义。