Evaluation of travoprost as adjunctive therapy in patients with uncontrolled intraocular pressure while using timolol 0.5%

This study was presented in part at the Annual Meeting of the American Glaucoma Society, Newport Beach, California, March 2, 2001, and at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, May 2, 2001.
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Abstract

PURPOSE: To evaluate the intraocular pressure-lowering efficacy and safety of travoprost 0.0015% and 0.004%, dosed daily in the evening compared with vehicle, in patients with open-angle glaucoma or ocular hypertension, whose intraocular pressure was not adequately controlled on timolol 0.5% twice daily (twice daily).

METHODS: Subjects who qualified at screening began a run-in period dosing timolol twice daily for 3 weeks. If the subjects had an intraocular pressure of 24 to 36 mm Hg at 8 am and 21 to 36 mm Hg at 10 am and 4 pm in at least one eye on timolol, they were randomized to one of two concentrations of travoprost (0.0015% or 0.004%) or vehicle solution every day and were followed for 6 months. Four hundred twenty-six subjects were randomized. The mean intraocular pressure at 8 am, 10 am, and 4 pm in the patient’s eye with the higher intraocular pressure was used for the analysis.

RESULTS: Mean baseline values (25 mm Hg) for subjects at eligibility (while maintained on timolol) were not significantly different (P < .0001) among the treatment groups. The intraocular pressure was lowered an additional −5.7 to −7.2 mm Hg and −5.1 to −6.7 mm Hg in the travoprost 0.004% and 0.0015% concentrations, respectively. These changes were significantly (P ≤ .0001) different from the vehicle group (−1.3 to −2.8 mm Hg). The intraocular pressure range on treatment at all visit times over the 6-month treatment period ranged from 17.9 to 19.2 mm Hg for travoprost 0.004% and 18.3 to 20.1 mm Hg for travoprost 0.0015% compared with 22.4 to 24.1 mm Hg for vehicle. Average hyperemia scores ranged from trace to mild (mean 0.5 on a scale of 0 = none/trace; 1= mild; 2 = moderate; 3 = severe) for all treatment groups. No iris pigmentation changes were observed in any patient during this study. There were no clinically or statistically significant changes from baseline in visual acuity, ocular cells and flare, fundus parameter, cup-to-disk ratio and visual field between the treatment groups. There were no serious adverse events reported for any treatment group.

CONCLUSIONS: Travoprost produced clinically relevant and statistically significant additional intraocular pressure reductions from baseline when used adjunctively with timolol in subjects with open-angle glaucoma or ocular hypertension.

Section snippets

Methods

This prospective, multicenter, double-masked, randomized, parallel group study was conducted in accordance with the principles set forth in the Declaration of Helsinki. Subjects or their legal representative read, signed, and dated an institutional review board-approved consent form before undergoing a screening examination and participation in the study.

The study population consisted of subjects of any race and either sex. Women were required to be 1 year postmenopausal or to have been

Results

Four hundred twenty-seven subjects were randomized to travoprost 0.0015% (n = 142), travoprost 0.004% (n = 145), and vehicle (n = 139). Seventeen subjects had no data recorded while on treatment and thus were excluded from the intent-to-treat analysis (three in 0.0015%, nine in 0.004%, and five in vehicle groups).

Sixty-five subjects were excluded from the per protocol analysis because of protocol violations (20 in 0.0015%, 23 in 0.004%, and 22 in vehicle groups), which included nonqualifying

Discussion

To our knowledge, this is the largest and longest controlled, clinical trial assessing the ability of a prostaglandin analogue to further lower intraocular pressure when used adjunctively with timolol. Significant additional intraocular pressure reductions from baseline of up to 28% were observed with both concentrations of travoprost in subjects whose intraocular pressure remained high despite timolol therapy.

Although the mechanism(s) of action of travoprost has not been determined, it is

Travoprost study group investigators

Walter Atlas, MD, Nalle Clinic, Charlotte, NC 28207; Mark G. Bearman, MD, Eastern Ophthalmic Associates, Inc, Birmingham, AL 35235; Donald Brotherman, MD, Texas Eye Care Associates, Dallas, TX 75234; Delmar Caldwell, MD, Tulane University Medical Center, New Orleans, LA 02112; Robert Caine, MD, Access Eye Centers, Fredericksburg, VA 22405; Hersh Chopra, MD, Georgia Eye Specialists, Marietta, GA 30060; Charles Eugene Cox, MD, Fort Myers, FL 33901; E. Randy Craven, MD, Glaucoma Consultants of CO,

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This study was supported by Alcon Research, Ltd. Dr Orengo-Nania was a clinical investigator for this study and has no proprietary interest in travoprost or any other product in this manuscript. Proprietary rights for travoprost are retained by Alcon Research, Ltd., 6201 S. Freeway, Fort Worth, Texas 76134.

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