Once-Daily Netarsudil Versus Twice-Daily Timolol in Patients With Elevated Intraocular Pressure: The Randomized Phase 3 ROCKET-4 Study

被引：67

作者：

Khouri, Albert S. ^{[1
]}

Serle, Janet B. ^{[2
]}

Bacharach, Jason ^{[3
,9
]}

Usner, Dale W. ^{[4
]}

Lewis, Richard A. ^{[5
,6
,7
,8
]}

Braswell, Puiwah ^{[5
,6
,7
]}

Kopczynski, Casey C. ^{[5
,6
,7
]}

Heah, Theresa ^{[5
,6
,7
]}

Bacharach, Jason ^{[3
,9
]}

Benza, Robert ^{[10
]}

Boyle, John W. ^{[11
]}

Butler, Michelle ^{[12
]}

Cacioppo, Leonard Robert ^{[13
]}

Cardona, Jose F. ^{[14
]}

Colborn, Valerie A. ^{[15
]}

Day, Douglas G. ^{[16
]}

Douglass, David T. ^{[17
]}

El-Harazi, Sherif M. ^{[18
]}

Ghate, Deepta ^{[19
]}

Hartman, Carl ^{[20
]}

Haverly, Robert F. ^{[21
]}

Katzman, Barry ^{[22
]}

Kim, Max ^{[23
]}

Koo, Edward Y. ^{[24
]}

Korenfeld, Michael S. ^{[25
]}

Kwapiszeski, Bradley ^{[26
]}

Lane, Lydia ^{[27
]}

Lin, Christopher ^{[28
]}

Logan, Andrew Gardner ^{[29
]}

Lozier, Jeffrey Raymond ^{[30
]}

McQuirter, Henry ^{[31
]}

Mundorf, Thomas K. ^{[32
]}

Olander, Kenneth ^{[33
]}

Ou, Richard J. ^{[34
]}

Panzo, Gregory J. ^{[35
]}

Peace, James H. ^{[36
]}

Protzko, Eugene E. ^{[37
]}

Ritch, Robert ^{[38
]}

Sall, Kenneth ^{[39
]}

Schechter, Barry A. ^{[40
]}

Seltzer, Samuel Eric ^{[41
]}

Shah, Pankajkumar G. ^{[42
]}

Sharpe, Elizabeth ^{[43
]}

Shettle, Philip Lee ^{[44
]}

Shulman, David G.

Singh, Inder Paul ^{[45
]}

Smith, Stacy R. ^{[46
]}

Smith, Stephen E. ^{[47
]}

Smyth-Medina, Robert John ^{[48
]}

Sorenson, Robert C. ^{[49
]}

机构：

[1] Rutgers New Jersey Sch Med, Newark, NJ USA

[2] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[3] North Bay Eye Associates, Sonoma Cty, CA USA

[4] Stat & Data Corp, Tempe, AZ USA

[5] Aerie Pharmaceut Inc, Irvine, CA USA

[6] Aerie Pharmaceut Inc, Bedminster, NJ USA

[7] Aerie Pharmaceut Inc, Durham, NC USA

[8] Sacramento Eye Consultants, Sacramento, CA USA

[9] North Bay Eye Associates Inc, Petaluma, CA USA

[10] Apex Eye, Cincinnati, OH USA

[11] Gulf South Eye Associates, Metairie, LA USA

[12] Glaucoma Associates Texas, Dallas, TX USA

[13] Hernando Eye Inst, Brooksville, FL USA

[14] Indago Res & Hlth Ctr Inc, Hialeah, FL USA

[15] Colborn Eye Care, Lillington, NC USA

[16] Coastal Res Associates LLC, Roswell, GA USA

[17] Eye Ctr Northeast, Bangor, ME USA

[18] Lugene Eye Inst, Glendale, CA USA

[19] UNMC Truhlsen Eye Inst, Omaha, NE USA

[20] Southern Calif Eye Physicians & Associates, Long Beach, CA USA

[21] Laser Eye Surg Erie, Erie, PA USA

[22] West Coast Eye Care Associates, San Diego, CA USA

[23] Arizona Glaucoma Specialists, Phoenix, AZ USA

[24] Peninsula Ophthalmol Grp, Burlingame, CA USA

[25] Comprehens Eye Care Ltd, Washington, MO USA

[26] Heart Amer Eye Care, Shawnee Mission, KS USA

[27] Little Rock Eye Clin LLP, Little Rock, AR USA

[28] Shasta Eye Med Grp Inc, Redding, CA USA

[29] Logan Ophthalm Res LLC, Tamarac, FL USA

[30] Arch Hlth Partners, Poway, CA USA

[31] Eye Specialty Grp, Memphis, TN USA

[32] Mundorf Eye Ctr, Charlotte, NC USA

[33] Univ Eye Specialists, Maryville, TN USA

[34] Houston Eye Associates, Houston, TX USA

[35] Mid Florida Eye Ctr PA, Mt Dora, FL USA

[36] United Med Res Inst, Inglewood, CA USA

[37] Seidenberg Protzko Eye Associates, Havre De Grace, MD USA

[38] New York Eye & Ear Infirm, New York, NY 10003 USA

[39] Sall Res Med Ctr, Artesia, CA USA

[40] Florida Eye Microsurg Inst Inc, Boynton Beach, FL USA

[41] Carolinas Ctr Sight PC, Florence, SC USA

[42] DCT Shah Res LLC, Mission, TX USA

[43] Glaucoma Consultants & Ctr Eye Res PA, Mt Pleasant, MI USA

[44] Shettle Eye Res Inc, Largo, FL USA

[45] Eye Ctr Racine & Kenosha Ltd, Kenosha, WI USA

[46] Mt Valley Eye Inst, Salt Lake City, UT USA

[47] Eye Associates Ft Myers, Ft Myers, FL USA

[48] North Valley Eye Med Grp Inc, Mission Hills, CA USA

[49] Inland Eye Specialists, Hemet, CA USA

[50] Ophthalm Consultants Long Isl, Lynbrook, NY USA

来源：

AMERICAN JOURNAL OF OPHTHALMOLOGY | 2019年 / 204卷

关键词：

GLAUCOMA PROGRESSION; OCULAR HYPERTENSION; LATANOPROST; AR-13324; EFFICACY; SAFETY;

D O I：

10.1016/j.ajo.2019.03.002

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety of netarsudil once daily (QD) and timolol twice daily (BID). DESIGN: Double-masked, randomized, phase 3, noninferiority study. METHODS: Patients with open-angle glaucoma or ocular hypertension (unmedicated baseline IOP > 20 to < 30 mm Hg at 8:00 AM) were randomized to netarsudil ophthalmic solution 0.02% QD (PM) or timolol ophthalmic solution 0.5% BID. The primary endpoint was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3 in patients with baseline IOP < 25 mm Hg (per-protocol population). Safety was recorded over the 6-month treatment period. RESULTS: A total of 186 patients from each treatment arm were included in the primary efficacy analysis. Netarsudil QD met the criteria for noninferiority to timolol BID. Mean treated IOP ranged from 16.3 to 17.9 mm Hg for netarsudil and 16.7 to 17.6 for timolol, with mean reductions from baseline of 3.9 to 4.7 mm Hg and 3.8 to 5.2 mm Hg, respectively. In prespecified secondary analyses, netarsudil demonstrated noninferiority to timolol in patients with baseline IOP < 27 mm Hg and < 30 mm Hg. The IOP-lowering effects of netarsudil were sustained over 6 months of treatment. No treatment-related serious adverse event (AE) was reported for either study drug. However, statistically significant reductions in mean heart rate were recorded at all study visits for the timolol group. The most frequent ocular AE among netarsudil-treated patients was conjunctival hyperemia (47.9%), which was predominately mild. CONCLUSIONS: Netarsudil QD (PM), a first-in-class IOP-lowering medication, was noninferior to timolol BID and was associated with tolerable ocular AEs. (Am J Ophthalmol 2019;204:97-104. (C) 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

引用

页码：97 / 104

页数：8

共 31 条

[1]

Aerie Pharmaceuticals Inc,, 2017, RHOPRESSA NET OPHTH

[2]

Alward WL, 1998, AM J OPHTHALMOL, V126, P498

[3]

[Anonymous], 2017, CORDARONE AM HCI PRE

[4]

[Anonymous], 2016, TIMOPTIC 0 25 0 5 TI