Icahn School of Medicine at Mount Sinai, New York, New York.
Wills Eye Hospital, Philadelphia, Pennsylvania.
Am J Ophthalmol. 2018 Feb;186:116-127. doi: 10.1016/j.ajo.2017.11.019. Epub 2017 Dec 1.
To evaluate the efficacy and ocular and systemic safety of netarsudil 0.02% ophthalmic solution, a rho-kinase inhibitor and norepinephrine transporter inhibitor, in patients with open-angle glaucoma and ocular hypertension.
Double-masked, randomized noninferiority clinical trials: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).
After a washout of all pre-study ocular hypotensive medications, eligible patients were randomized to receive netarsudil 0.02% once daily (q.d.), timolol 0.5% twice a day (b.i.d.), and (ROCKET-2 only) netarsudil 0.02% b.i.d. Data through 3 months from both studies are provided in this report.
Enrolled into the 2 studies were 1167 patients. Treatment with netarsudil q.d. produced clinically and statistically significant reductions from baseline intraocular pressure (P < .001), and was noninferior to timolol in the per-protocol population with maximum baseline IOP < 25 mm Hg in both studies (ROCKET-2, primary outcome measure and population, ROCKET-1, post hoc outcome measure). Netarsudil b.i.d. was also noninferior to timolol (ROCKET-2). The most frequent adverse event was conjunctival hyperemia, the incidence of which ranged from 50% (126/251, ROCKET-2) to 53% (108/203, ROCKET-1) for netarsudil q.d., 59% (149/253, ROCKET-2) for netarsudil b.i.d., and 8% (17/208, ROCKET-1) to 11% (27/251, ROCKET-2) for timolol (P < .0001 for netarsudil vs timolol).
In 2 large, randomized, double-masked trials reported here, once-daily dosing of netarsudil 0.02% was found to be effective and well tolerated for the treatment of patients with ocular hypertension and open-angle glaucoma. The novel pharmacology and aqueous humor dynamic effects of this molecule suggest it may be a useful addition to the armamentarium of ocular hypotensive medications.
评估 rho 激酶抑制剂和去甲肾上腺素转运体抑制剂奈立定（netarsudil）0.02%滴眼剂治疗开角型青光眼和高眼压症患者的疗效和眼安全性及全身安全性。
双盲、随机非劣效性临床试验：Rho 激酶升高眼压治疗试验 1 和 2（ROCKET-1 和 ROCKET-2）。
在所有研究前降眼压药物洗脱后，符合条件的患者被随机分配接受奈立定 0.02%，每日 1 次（q.d.），噻吗洛尔 0.5%，每日 2 次（b.i.d.）和（仅 ROCKET-2）奈立定 0.02%，每日 2 次（b.i.d.）。本报告提供了这两项研究中 3 个月的数据。
共有 1167 名患者入组这两项研究。奈立定 q.d.治疗从基线眼压（IOP）产生了临床和统计学显著降低（P <.001），在两项研究中最大基线 IOP < 25mm Hg 的方案人群中，与噻吗洛尔相比具有非劣效性（ROCKET-2，主要结局指标和人群，ROCKET-1，事后结局指标）。奈立定 b.i.d.也与噻吗洛尔具有非劣效性（ROCKET-2）。最常见的不良反应是结膜充血，发生率范围为奈立定 q.d.组 50%（126/251，ROCKET-2）至 53%（108/203，ROCKET-1），奈立定 b.i.d.组 59%（149/253，ROCKET-2），噻吗洛尔组 8%（17/208，ROCKET-1）至 11%（27/251，ROCKET-2）（与噻吗洛尔相比，奈立定的 P <.0001）。
在本报告的两项大型、随机、双盲试验中，每天 1 次使用奈立定 0.02%滴眼剂治疗高眼压症和开角型青光眼患者，结果显示有效且耐受良好。该分子的新型药理学和房水动力学效应表明，它可能是眼降压药物治疗的有用选择。
