Comparison of Topical Travoprost Eye Drops Given Once Daily and Timolol 0.5% Given Twice Daily in Patients with Open-Angle Glaucoma or Ocular Hypertension *Ivan Goldberg, FRANZCO, †José Cunha-Vaz, MD, ‡Jan-Erik Jakobsen, MD, §Jean-Philippe Nordmann, MD, PhD,  Elisabeth Trost, MSc,  E. Kenneth Sullivan, PhD, and the International Travoprost Study Group *Sydney Eye Hospital, Sydney, Australia; †Associac ¸ao para investigac ¸ao biomedica e inovac ¸ao em luz e imagem, Coimbra, Portugal; ‡Ullevål Sykehus, Oslo, Norway; §Hôpital des Quinze-Vingts, Paris, France,  Alcon Research Limited, Fort Worth, Texas Purpose: This 9-month study compared the intraocular pressure (IOP)-lowering efficacy and safety of once-daily travoprost ophthalmic solutions (0.0015% and 0.004%) with twice-daily timolol 0.5%. Patients and Methods: This study was conducted using a double-masked, ran- domized, parallel-group design; adult patients with open-angle glaucoma or ocular hypertension (IOP between 24 and 36 mm Hg, inclusive at 9 AM and between 21 and 36 mm Hg, inclusive, at 11 AM and 4 PM on two eligibility visits after an appropriate washout of previous treatments). In both eyes, the travoprost vehicle (placebo) was instilled at 9 AM and travoprost (0.0015% or 0.004%) was instilled at 9 PM, or timolol 0.5% was instilled at both times. The primary efficacy variable was mean IOP mea- sured at 9 AM, 11 AM, and 4 PM at baseline and follow-up visits. Results: Five hundred seventy-three patients were randomized to the study treat- ments. Mean IOP, which was combined across study visits, was lower with travoprost 0.004% than with timolol 0.5% at 9 AM (P  0.0246), 11 AM (P  0.0039), and 4 PM (P  0.0004). Intraocular pressure was lower with travoprost 0.004% than with travoprost 0.0015% at 11 AM (P  0.0314), the time of peak drug activity. Mean IOP was consistently lower with travoprost 0.0015% than with timolol 0.5%. Mean IOP reductions from baseline were significantly (P  0.0001) greater with travoprost 0.004% (8.0–8.9 mm Hg) than with timolol 0.5% (6.3–7.9 mm Hg). The most frequent related adverse events were hyperemia, pruritus, discomfort, pain, and iris pigmenta- tion changes. The local tolerance was better in the timolol group compared with patients receiving travoprost. There were no serious unexpected treatment-related ad- verse events in any group. Conclusions: Travoprost 0.004% reduced diurnal mean intraocular pressure sig- nificantly more than timolol 0.5%. Both concentrations of travoprost were well toler- ated and safe for use in patients with open-angle glaucoma or ocular hypertension. Key Words: Glaucoma—Ocular hypertension—Timolol—Travoprost. Prostaglandin (PGF 2 ) analogues comprise a new class of ocular hypotensive agents. They reduce intraoc- ular pressure (IOP) at least as effectively as -adrenergic antagonists, which are the standard treatment for open- angle glaucoma and ocular hypertension, but lack their undesirable systemic effects. 1 Travoprost is an esterified PGF 2 analogue that on instillation is hydrolyzed in the cornea to the biologically active free acid. The ester prodrug enhances penetration of the free acid into aqueous humor. 2 The free-acid par- ent of travoprost (AL-5848, which is structurally similar to fluprostenol and other prostaglandin PGF 2 ana- logues) manifests preferential affinity and full agonist Received February 19, 2001; accepted for publication April 24, 2001. Supported financially by Alcon Research Limited, Fort Worth, TX. Address correspondence and reprint requests to Dr. Ivan Goldberg, Floor 4, 187 Macquarie Street, Sydney NSW 2000, Australia Journal of Glaucoma 10:414–422 © 2001 Lippincott Williams & Wilkins, Inc. 414