目的:已经发现二氢乳清酸脱氢酶(DHODH)的抑制剂是有效的抗炎剂。最近,已经开发了DHODH抑制剂的局部制剂(KIO-101滴眼剂)。本研究的目的是评估KIO-101滴眼液在健康志愿者(HV)和结膜充血患者中的安全性和耐受性。
方法:这项研究是在双掩模中进行的,安慰剂对照,随机化,由两部分组成的平行组设计。在第一部分,HV接受单次和多次滴注(每天四次,连续12天)递增剂量为0.05%的KIO-101滴眼液,0.15%,和0.30%,分别。第II部分在结膜充血患者中进行,该患者连续12天每天两次接受0.15%KIO-101滴眼液。对所有参与者进行眼科和全身安全性检查。在第二部分,进行了眼部充血分级和眼表疾病指数(OSDI)问卷。
结果:第一部分有24例HV,第二部分有21例患者。KIO-101滴眼液在所有受试者中均具有良好的耐受性。无严重不良事件(SAE)发生,报告的所有AE均为一过性,被认为是轻度至中度。在最高剂量队列(0.30%),多次滴注后,两名受试者发生鼻出血。在第二部分,用0.15%KIO-101治疗12天后,治疗组结膜充血减少-1.1±0.27分,安慰剂组减少-0.6±0.79分(p=0.0385).治疗组OSDI由47.9±18.7降至27.6±19.13分,而在安慰剂组,发生了从41.3±12.08到27.3±18.63点的变化。
结论:在HVs和结膜充血患者中,采用低剂量和中等剂量的局部KIO-101滴眼液的12天治疗方案是安全且耐受性良好的。获得的结果表明结膜充血减少的早期迹象。
OBJECTIVE: Inhibitors of dihydroorotate dehydrogenase (DHODH) have been found to be potent anti-inflammatory agents. Recently, a topical formulation (KIO-101 eye drops) of a DHODH inhibitor has been developed. The aim of the present study was to evaluate the safety and tolerability of KIO-101 eye drops in Healthy Volunteers (HVs) and patients with conjunctival hyperemia.
METHODS: The study was carried out in a double-masked, placebo-controlled, randomized, parallel-group design with two parts. In part I, HVs received single and multiple instillations (four times daily for 12 consecutive days) of KIO-101 eye drops in ascending doses of 0.05%, 0.15%, and 0.30%, respectively. Part II was conducted in patients with conjunctival hyperemia who received 0.15% KIO-101 eye drops twice daily for 12 consecutive days. Ophthalmic and systemic safety examinations were performed on all participants. In part II, ocular hyperemia grading and an ocular surface disease index (OSDI) questionnaire were performed.
RESULTS: 24 HVs participated in part I and 21 patients in part II. KIO-101 eye drops were well tolerated in all subjects. No serious adverse events (SAEs) occurred, and all AEs that were reported were transient and considered mild to moderate. In the highest dose cohort (0.30%), epistaxis occurred in two subjects after multiple instillations. In part II, after 12 days treatment with 0.15% KIO-101, conjunctival hyperemia decreased by -1.1 ± 0.27 points in the treatment and -0.6 ± 0.79 points in the placebo group (p = 0.0385). OSDI decreased from 47.9 ± 18.7 to 27.6 ± 19.13 points in the treatment group, while in the placebo group, a change from 41.3 ± 12.08 to 27.3 ± 18.63 points occurred.
CONCLUSIONS: A 12-day treatment regimen with topical KIO-101 eye drops at low and mid doses was safe and well tolerated in both HVs and patients with conjunctival hyperemia. The obtained results point towards an early sign of reduction in conjunctival hyperemia.