A 1-Year Study to Compare the Efficacy and Safety of Once-Daily Travoprost 0.004%/Timolol 0.5% to Once-Daily Latanoprost 0.005%/Timolol 0.5% in Patients with Open-Angle Glaucoma or Ocular Hypertension
Authors: Topouzis F. , Melamed S. , Danesh-meyer H. , Wells A.P. , Kozobolis V. , Wieland H. , Andrew R. , Wells D. ,   THE INTERNATIONAL TRAVOPROST/TIMOLOL STUDY GROUP, Kozobolis Vassilios P. , Maskaleris George , Detorakis Efstathios , Topouzis Fotis , Anastasopoulos Eleftherios , Pappas Theofanis , Kandarakis Artemios , Koutroumanos John , Aspiotis Miltiadis , Pappa Chrisavgi , Vaikoussis Emmanuel , Paschalidis Thrassyvoulos , Bournas Panagiotis , Kazatzis Nikos , Goldberg Ivan , Graham Stuart , Healey Paul , Rait Julian Lockhart , Bank Allan , Healey Paul R. , Crowston Jonathan , Guzowski Magdalena , Covar Ranier , Lee Anne , Wan Jen , Azar Domit , Stadion Paul , Lizin François , De Groot Veva , Schraepen Patrick , Reyntjens Bruno , Kestelynstevens Anna-Maria , Witters Fien , Teesalu Pait , Kuus Imbi , Oll Maris , Aamer Ulle , Alas Elo , Pastak Marko , Delbosc Bernard Y.C. , Gerstenberger Albrecht , Jungmann Peter , Hamacher Ludwig T. , Hellmair Ursula , Bayer Andreas U.M. , Foerster Wolfgang , Christ Thomas , Reibaldi Alfredo , Uva Maurizio , Longo Antonio , Lombardo Daniela , Trimarchi Fernando , Milano Giovanni , Clemente Antonella , Rossi M. Gemma , Scatassi Ilaria , Montemurro Francesca , Grignolo Federico M. , Brogliatti Beatrice , Rolle Teresa , Favero Cristina , Giacosa Elisabetta , Fornero Angela , Melamed Sh-lomo , Goldenfeld Mordehai , Verbin Hani , Vilner Zohar , Knaan Ran , Moroz Iris , Geyer Orna , Segev Eitan , Kurtz Shimon , Neudorfer Meira , Shemesh Gabi , Zayit Shiri , Volksone Lasma , Karlsone Lija , Laganovska Guna , Baumane Kristine , Egite Ilze , Januleviciene Ingrida , Kuzmiene Loreta , Danesh-Meyer Helen , Wells Anthony P. , Riley Andrew , Bedggood Anthony , Long Helen , Ashraff Nina , Abrantes Pedro A.L. , Reina Maria , Silva Jose Pedro , Ilharco Joao , Chew Paul Tec Kwan , Thean Lennard , Ang Lim Boon , Manuel Joseph , Chee Loon Seng , Tan Clement , Ming Yeong Suet , Seah Steve Kah Leng , Oen Francis , Ang Lim Boon , Husain Rahat , Tian Hoh Sek , Tin Aung , Sánchez Garcia Julián , Feijoo Julián García , Martínez de La Casa José María , Gómez Alfredo Castillo , López Francisco Manuel Honrubia , Llorens Vicente Polo , Júlvez Luis Pablo , Luisa Maria , Martínez Gómez , Manuel José , Póvez Larrosa , Arias-Puente Alfonso , Carrasco Carmen , del Carmen Maria , Yolanda García , Alba Andrés , Gurdiel Elena , Dorronzoro Emilio , Muniesa Maria Jesús , Lu Da-Wen , Clearkin Louis G. , Patwala Yogesh 
Published: January 2018

Purpose

The objective of the study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004%/timolol 0.5% ophthalmic solution (Trav/Tim) to latanoprost 0.005%/timolol 0.5% ophthalmic solution (Lat/Tim), dosed once daily in the morning, in patients with open-angle glaucoma (OAG) or ocular hypertension (OH).

Methods

This was a randomized, double-masked, multicenter, parallel group, active-controlled study conducted at 41 sites. At the eligibility visit the patients were randomized (1:1) to the assigned masked medication if they met inclusion/exclusion criteria, and the mean IOP values in the eligible eyes were ≥24 mmHg at 9 AM and ≥21 mmHg at 11 AM and 4 PM. Patients were excluded if the mean IOP in either eye was >36 mmHg. Patients were instructed to administer the assigned medication each morning at 9 AM. During the treatment phase of the study, IOP was measured at 9 AM at week 2, week 6, month 3, and month 9. At the month 6 and month 12 visits, IOP was measured at 9 AM, 11 AM, and 4 PM. Statistical methods included a repeated measures analysis of variance (ANOVA); to test for noninferiority, a 95% confidence interval for the treatment group difference was constructed based on the ANOVA results for each time point at month 12.

Results

Patients (n=408) with OAG or OH were enrolled at 41 sites. One patient withdrew prior to receiving medication so 207 in the Trav/Tim group and 200 in the Lat/Tim group were evaluable for safety. Baseline demographic characteristics as well as IOP values showed no statistical differences between the two groups. Trav/Tim provided lower mean IOP values than Lat/Tim that were statistically significant at the week 2 9 AM (p=0.0081), month 6 9 AM (p=0.0056), and month 6 11 AM (p=0.0128) time points and at 9 AM time point pooled across all visits (p=0.0235) when mean IOP was 0.6 mmHg lower in the Trav/Tim group. Treatment-related adverse events were mild in both groups. Although hyperemia was reported from a higher percentage of patients in Trav/Tim group, differences in average hyperemia scores between the two groups were not considered clinically relevant.

Conclusions

Travoprost 0.004%/timolol 0.5% ophthalmic solution produced mean IOP levels that are statistically noninferior to latanoprost 0.005%/timolol 0.5% ophthalmic solution. Furthermore, at 9:00 AM, 24 hours after dosing, IOP was statistically lower for travoprost 0.004%/timolol 0.5% pooled across all visits. Travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution is an effective treatment for reducing IOP and it is safe and well-tolerated in patients with OAG or OH. (Eur J Ophthalmol 2007; 17: 183–90)