Advertisement

Advances in Therapy

, Volume 35, Issue 6, pp 796–808 | Cite as

Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension

  • Katsuyoshi SuzukiEmail author
  • Naomi Otsuka
  • Hiroko Hizaki
  • Masayo Hashimoto
  • Yasuaki Kuwayama
  • On behalf of the Tafluprost/Timolol Versus Latanoprost/Timolol (TTVLT) Study Group
Original Research

Abstract

Introduction

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).

Methods

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.

Results

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.

Conclusion

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.

Trial Registration

UMIN Clinical Trials Registry Identifier, UMIN000023862.

Funding

Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Keywords

Beta-blocker Efficacy Intraocular pressure Latanoprost Ocular hypertension Ophthalmology Primary open-angle glaucoma Prostaglandin Safety Tafluprost 

Notes

Acknowledgements

We wish to express our gratitude to the participants of the study.

Funding

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.

Medical Writing

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.

Authorship

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.

Authorship Contributions

Please refer to Supplementary Table 1 for the full list of participants in the Tafluprost/Timolol Versus Latanoprost/Timolol (TTVLT) Study Group.

Disclosures

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).

Data Availability

The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

12325_2018_718_MOESM1_ESM.pdf (184 kb)
Supplementary material 1 (PDF 183 kb)

References

  1. 1.
    Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–7.CrossRefGoogle Scholar
  2. 2.
    Marquis RE, Whitson JT. Management of glaucoma: focus on pharmacological therapy. Drugs Aging. 2005;22:1–21.CrossRefGoogle Scholar
  3. 3.
    National Institute for Health and Care Excellence. Glaucoma: diagnosis and management, NICE guideline [NG81] 2017. https://www.nice.org.uk/guidance/ng81.
  4. 4.
    Newman-Casey PA, Robin AL, Blachley T, et al. The most common barriers to glaucoma medication adherence: a cross-sectional survey. Ophthalmology. 2015;122:1308–16.CrossRefGoogle Scholar
  5. 5.
    Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311:1901–11.CrossRefGoogle Scholar
  6. 6.
    Tsai JC, McClure CA, Ramos SE, Schlundt DG, Pichert JW. Compliance barriers in glaucoma: a systematic classification. J Glaucoma. 2003;12:393–8.CrossRefGoogle Scholar
  7. 7.
    Hollo G, Topouzis F, Fechtner RD. Fixed-combination intraocular pressure-lowering therapy for glaucoma and ocular hypertension: advantages in clinical practice. Exp Opin Pharmacother. 2014;15:1737–47.CrossRefGoogle Scholar
  8. 8.
    European Glaucoma Society. Terminology and guidelines for glaucoma, 4th edition—Chapter 3. Br J Ophthalmol. 2017;101:129–91.Google Scholar
  9. 9.
    Russ HH, Nogueira-Filho PA, Barros Jde N, et al. Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial. Clinics (Sao Paulo). 2013;68:1318–24.CrossRefGoogle Scholar
  10. 10.
    Shoji T, Sato H, Mizukawa A, et al. Hypotensive effect of latanoprost/timolol versus travoprost/timolol fixed combinations in NTG patients: a randomized, multicenter, crossover clinical trial. Invest Ophthalmol Vis Sci. 2013;54:6242–7.CrossRefGoogle Scholar
  11. 11.
    Topouzis F, Melamed S, Danesh-Meyer H, et al. 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. Eur J Ophthalmol. 2007;17:183–90.CrossRefGoogle Scholar
  12. 12.
    Kanamoto T, Kiuchi Y, Tanito M, et al. Comparison of the toxicity profile of benzalkonium chloride-preserved tafluprost and SofZia-preserved travoprost applied to the ocular surface. J Ocul Pharmacol Ther. 2015;31:156–64.CrossRefGoogle Scholar
  13. 13.
    Shimmura S, Ono M, Shinozaki K, et al. Sodium hyaluronate eyedrops in the treatment of dry eyes. Br J Ophthalmol. 1995;79:1007–11.CrossRefGoogle Scholar
  14. 14.
    Li T, Lindsley K, Rouse B, et al. Comparative effectiveness of first-line medications for primary open-angle glaucoma. Ophthalmology. 2016;123:129–40.CrossRefGoogle Scholar
  15. 15.
    Aihara M. Clinical appraisal of tafluprost in the reduction of evaluated intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension. Clin Ophthalmol. 2010;4:163–70.CrossRefGoogle Scholar
  16. 16.
    Hollo G, Vuorinen J, Tuominen J, Huttunen T, Ropo A, Pfeiffer N. Fixed-dose combination of tafluprost and timolol in the treatment of open-angle glaucoma and ocular hypertension: comparison with other fixed-combination products. Adv Ther. 2014;31:932–44.CrossRefGoogle Scholar
  17. 17.
    Lou H, Wang H, Zong Y, Cheng JW, Wei RL. Efficacy and tolerability of prostaglandin-timolol fixed combinations: an updated systematic review and meta-analysis. Curr Med Res. 2015;31:1139–47.CrossRefGoogle Scholar
  18. 18.
    Konstas AG, Voudouragkaki IC, Boboridis KG, et al. 24-hour efficacy of travoprost, timolol BAK-free versus latanoprost, timolol fixed combinations in patients insufficiently controlled with latanoprost. Adv Ther. 2014;31:592–603.CrossRefGoogle Scholar
  19. 19.
    Fuwa M, Ueda K, Akaishi T, et al. Advantages of efficacy and safety of fixed-dose tafluprost/timolol combination over fixed-dose latanoprost/timolol combination. PLoS One. 2016;11:e0158797.CrossRefGoogle Scholar
  20. 20.
    Baudouin C, Labbé A, Liang H, Pauly A, Bringnole-Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010;29:312–34.CrossRefGoogle Scholar
  21. 21.
    Aihara M, Ikeda Y, Mizoue S, Arakaki Y, Kita N, Kobayashi S. Effect of switching to travoprost preserved with SofZia in glaucoma patients with chronic superficial punctate keratitis while receiving BAK-preserved latanoprost. J Glaucoma. 2016;25:e610–4.CrossRefGoogle Scholar
  22. 22.
    Aihara M, Oshima H, Araie M. Effects of SofZia-preserved travoprost and benzalkonium chloride-preserved latanoprost on the ocular surface—a multicentre randomized single-masked study. Acta Ophthalmol. 2013;91:e7–14.CrossRefGoogle Scholar
  23. 23.
    Suzuki K, Teranishi S, Sagara T, et al. Safety and efficacy of benzalkonium chloride-optimized tafluprost in Japanese glaucoma patients with existing superficial punctate keratitis. J Glaucoma. 2015;24:e145–50.CrossRefGoogle Scholar
  24. 24.
    Aihara M, Adachi M, Matsuo H, et al. Additive effects and safety of fixed combination therapy with 1% brinzolamide and 0.5% timolol versus 1% dorzolamide and 0.5% timolol in prostaglandin-treated glaucoma patients. Acta Ophthalmol. 2017;95:e720–6.CrossRefGoogle Scholar
  25. 25.
    Adriaens E, Remon JP. Mucosal irritation potential of personal lubricants relates to product osmolality as detected by the slug mucosal irritation assay. Sex Transm Dis. 2008;35:512–6.CrossRefGoogle Scholar
  26. 26.
    Tsai JC. A comprehensive perspective on patient adherence to topical glaucoma therapy. Ophthalmology. 2009;116:S30–6.CrossRefGoogle Scholar
  27. 27.
    Chen PP. Blindness in patients with treated open-angle glaucoma. Ophthalmology. 2003;110:726–33.CrossRefGoogle Scholar
  28. 28.
    Denis P, Lafuma A, Berdeaux G. Medical outcomes of glaucoma therapy from a nationwide representative survey. Clin Drug Investig. 2004;24:343–52.CrossRefGoogle Scholar
  29. 29.
    Forsman E, Kivela T, Vesti E. Lifetime visual disability in open-angle glaucoma and ocular hypertension. J Glaucoma. 2007;16:313–9.CrossRefGoogle Scholar

Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2018

Authors and Affiliations

  • Katsuyoshi Suzuki
    • 1
    Email author
  • Naomi Otsuka
    • 2
  • Hiroko Hizaki
    • 2
  • Masayo Hashimoto
    • 2
  • Yasuaki Kuwayama
    • 3
  • On behalf of the Tafluprost/Timolol Versus Latanoprost/Timolol (TTVLT) Study Group
  1. 1.Suzuki Eye ClinicYamaguchiJapan
  2. 2.Santen Pharmaceutical Co., Ltd.OsakaJapan
  3. 3.Fukushima Eye ClinicOsakaJapan

Personalised recommendations