Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension
This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM).
This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire.
In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n = 60) or LAT/TIM (n = 55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4–6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group.
TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores.
UMIN Clinical Trials Registry Identifier, UMIN000023862.
Santen Pharmaceutical Co., Ltd., Osaka, Japan.
KeywordsBeta-blocker Efficacy Intraocular pressure Latanoprost Ocular hypertension Ophthalmology Primary open-angle glaucoma Prostaglandin Safety Tafluprost
We wish to express our gratitude to the participants of the study.
Sponsorship for this study and article processing charges were funded by Santen Pharmaceutical Co., Ltd., Osaka, Japan. All authors had full access to all of the data in these studies and take complete responsibility for the integrity of the data and accuracy of the data analysis.
We would like to thank Sheridan Henness, Sarah Greig, and Georgii Filatov, inScience Communications, Springer Healthcare, who wrote the outline and the first draft of this manuscript. This medical writing assistance was funded by Santen Pharmaceutical Co., Ltd.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.
Please refer to Supplementary Table 1 for the full list of participants in the Tafluprost/Timolol Versus Latanoprost/Timolol (TTVLT) Study Group.
Katsuyoshi Suzuki has received research grants and consultant fees from Alcon Pharmaceuticals, Kowa Pharmaceutical Co., Ltd., Nitten Pharmaceutical Co., Ltd., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., and Senju Pharmaceutical Co., Ltd.; lecture fees from Alcon Pharmaceuticals, AMO Japan, Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., and Senju Pharmaceutical Co., Ltd.; writing fees from Alcon Pharmaceuticals, Pfizer Japan Inc., and Santen Pharmaceutical Co., Ltd.; and non-financial support from Alcon Pharmaceuticals, AMO Japan, Kowa Pharmaceutical Co., Ltd., Nitten Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., and Senju Pharmaceutical Co., Ltd. Yasuaki Kuwayama has received consultant fees from Alcon Pharmaceuticals, Kowa Company, Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Santen Pharmaceutical Co., Ltd.; and lecture fees from Alcon Japan, Alcon Pharmaceuticals, Glaukos Corporation, Kowa Company, Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., and Senju Pharmaceutical Co., Ltd. Masayo Hashimoto is an employee of Santen Pharmaceutical Co., Ltd. Naomi Otsuka is an employee of Santen Pharmaceutical Co., Ltd. Hiroko Hizaki is an employee of Santen Pharmaceutical Co., Ltd.
Compliance with Ethics Guidelines
The ethics review boards of Santen Pharmaceutical Co., Ltd. and at study sites reviewed and approved the study protocol. All procedures performed in studies involving human participants were in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects (Ministry of Health, Labour and Welfare, Japan, 2014), the ethical standards of the institutional and/or national research committee, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study prior to commencement of any study procedures (visit 1; week − 4 ± 2 weeks).
The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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