Original article
Randomized Clinical Trial of the Efficacy and Safety of Preservative-free Tafluprost and Timolol in Patients With Open-Angle Glaucoma or Ocular Hypertension

https://doi.org/10.1016/j.ajo.2011.11.008Get rights and content

Purpose

To compare the efficacy and safety of tafluprost, a preservative-free (PF) prostaglandin analogue, with PF timolol in patients with open-angle glaucoma or ocular hypertension.

Design

Randomized, double-masked, multicenter clinical trial.

Methods

After discontinuation and washout of existing ocular hypotensive treatment, patients who had intraocular pressure (IOP) ≥23 and ≤36 mm Hg in at least 1 eye at the 08:00 hour time point were randomized 1:1 to 12 weeks of treatment with either PF tafluprost 0.0015% or PF timolol 0.5%. IOP was measured 3 times during the day (08:00, 10:00, 16:00 hours) at baseline and at weeks 2, 6, and 12. It was hypothesized that PF tafluprost would be noninferior to PF timolol over 12 weeks with regard to change from baseline IOP. The trial was powered for a noninferiority margin of 1.5 mm Hg at each of the 9 time points assessed.

Results

A total of 643 patients were randomized and 618 completed (PF tafluprost = 306, PF timolol = 312). IOPs at the 3 time points assessed during the baseline visit ranged from 23.8 to 26.1 mm Hg in the PF tafluprost group and 23.5 to 26.0 mm Hg in the PF timolol group. IOPs at the 3 time points assessed during the 12-week visit ranged from 17.4 to 18.6 mm Hg for PF tafluprost and 17.9 to 18.5 mm Hg for PF timolol. At all 9 time points, the upper limits of the 2-sided 95% confidence intervals for the difference between treatments in IOP lowering were less than the prespecified noninferiority margin. Similar percentages of PF tafluprost and PF timolol patients reported ocular pain/stinging/irritation (4.4% vs 4.6%) and pruritus (2.5% vs 1.5%). The percentages of PF tafluprost and PF timolol patients reporting conjunctival hyperemia were 4.4% vs 1.2% (nominal P = .016).

Conclusions

The IOP-lowering effect of PF tafluprost was noninferior to that of PF timolol. PF tafluprost is an efficacious and generally well-tolerated ocular hypotensive agent.

Section snippets

Design

This was a phase 3, multicenter, randomized, double-masked, parallel-group, 12-week, active comparator-controlled clinical trial comparing the efficacy and safety of PF tafluprost (0.0015%) and PF timolol maleate (0.5%) in glaucomatous or ocular hypertensive patients. The trial (Merck Protocol 001) was conducted from February 16, 2010 through September 17, 2010 at 40 sites in the United States, 6 sites in Spain, and 4 sites in Switzerland. A Scientific Advisory Committee composed of non-Merck

Patient Accounting and Demographics

The trial profile is shown in Supplemental Figure 1, (available at AJO.com). Of 643 randomized patients, 618 patients (96.1%) completed the study and 25 patients (3.9%) discontinued early. Main reasons for discontinuation were patient withdrawal (N = 12) or adverse events (N = 7; discussed below). The reasons for discontinuation were similar among the treatment groups.

A total of 31 patients were excluded from the per-protocol population used for the primary efficacy analysis, 21 in the PF

Discussion

The results from this phase 3 clinical trial in over 600 patients with open-angle glaucoma or ocular hypertension demonstrated that both PF tafluprost and PF timolol had a substantial IOP-lowering effect that was apparent after 2 weeks of treatment and was sustained throughout the 12-week assessment period. The IOP-lowering effect of PF tafluprost was noninferior to that of PF timolol at all visits and time points over 12 weeks. In addition, the upper boundary of the 95% CI was less than 0 at 4

References (34)

  • C.A. Webers et al.

    The intraocular pressure-lowering effect of prostaglandin analogs combined with topical β-blocker therapy: a systematic review and meta-analysis

    Ophthalmology

    (2010)
  • J.W. Cheng et al.

    Systematic review of intraocular pressure-lowering effects of adjunctive medications added to latanoprost

    Ophthalmic Res

    (2009)
  • S.S. Patel et al.

    LatanoprostA review of its pharmacological properties, clinical efficacy and tolerability in the management of primary open-angle glaucoma and ocular hypertension [Review]

    Drugs Aging

    (1996)
  • M.P. Curran

    Bimatoprost: a review of its use in open-angle glaucoma and ocular hypertension

    Drugs Aging

    (2009)
  • J.T. Whitson

    Travoprost - a new prostaglandin analogue for the treatment of glaucoma

    Expert Opin Pharmacother

    (2002)
  • C. Baudouin

    Detrimental effect of preservatives in eyedrops: implications for the treatment of glaucoma

    Acta Ophthalmol

    (2008)
  • P.J. Pisella et al.

    Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication

    Br J Ophthalmol

    (2002)

    • Cited by (43)

    • A comparison between the effect of topical tafluprost and latanoprost on intraocular pressure in healthy male guinea pigs

      2021, Journal of Exotic Pet Medicine
      Citation Excerpt :

      However, this reduction was significant only at 8:00 (-2.00 ± 1.15 mmHg, P-Value = 0.041), and 15:00 (-1.25 ± 0.50 mmHg, P-Value = 0.015) in the untreated eyes in group B. No significant reduction was observed in the IOP values of the untreated eyes in group A. Since the approval of tafluprost by the FDA in 2012, this drug had been introduced to the market in a BAK-preservative containing (Tapros®, Taflotan®) and a free-preservative formulation (Tapros Mini®, Taflotan-S®, Taflotan®, Saflutan®, Zioptan®) [31-33]. Although the short-term use of preservative containing ophthalmic solutions is considered to be safe with a low incidence of mild side effects, [34-36] due to the use of the glaucoma medications by patients in long-term therapy, we conducted this study using a preservative-free tafluprost solution (Zioptan®).

    • Technique

      2015, Glaucoma: Second Edition

    • Effect of Tafluprost on Endothelial Function-related Molecules and Hemorheological Parameters in Patients with Primary Open-angle Glaucoma

      2023, Research Square

    • The future of clinical trials of myopia control

      2023, Ophthalmic and Physiological Optics

    • Catania’s Primary Care of the Anterior Segment: Third Edition

      2023, Catania’s Primary Care of the Anterior Segment: Third Edition

    • Comparative efficacy and safety of preserved versus preservative-free beta-blockers in patients with glaucoma or ocular hypertension: a systematic review

      2022, Acta Ophthalmologica
    View all citing articles on Scopus

    Supplemental Material available at AJO.com.

    View full text
    Copyright © 2012 Elsevier Inc. All rights reserved.