A 6-Month Study Comparing Efficacy, Safety, and Tolerability of the Preservative-free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% versus Each of Its Individual Preservative-Free Components

Abstract

IntroductionThe efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015% and timolol 0.5% (once daily) were compared to those of the individual components (PF tafluprost 0.0015% once daily and PF timolol 0.5% twice daily) in patients with open-angle glaucoma or ocular hypertension inadequately controlled on prior timolol or prostaglandin monotherapy for 6 months.MethodsA stratified, double-masked, randomized, multicenter phase III study was conducted. A total of 189 prior timolol users were randomized within the timolol stratum (TS) to receive either FC (n = 95) or timolol 0.5% (TIM; n = 94). Furthermore, a total of 375 prior prostaglandin analog (PGA) users were randomized within the prostaglandin stratum (PS) to receive either FC (n = 188) or tafluprost 0.0015% (TAF; n = 187). To be eligible for participation in the study, the patients were required to have an intraocular pressure (IOP) of ≥22 mmHg when on timolol (TIM) or of ≥20 mmHg when on PGA in either treated eye at the screening and end-of-run-in visits. In addition to these, the study included visits at baseline, 2 and 6 weeks, 3 and 6 months and at a post-study visit. IOP was measured at 8 a.m., 10 a.m., 4 p.m., and 8 p.m.ResultsIn the TS, a significant reduction from baseline IOP was seen with FC and TIM throughout the study. Average diurnal IOP change from baseline at month 3 was −8.55 mmHg (32%) for FC and −7.35 mmHg (28%) for TIM. The model-based treatment difference (FC–TIM) was −0.885 mmHg [95% confidence interval (CI) −1.745 to −0.024; p = 0.044] demonstrating the superiority of FC over TIM. In the PS, a significant reduction in IOP was seen with both FC and TAF throughout the study. The average diurnal IOP change from baseline at month 3 was −8.61 mmHg (33%) for FC and −7.23 mmHg (28%) for TAF. The model-based treatment difference (FC–TAF) was −1.516 mmHg (95% CI −2.044 to −0.988; p < 0.001) demonstrating the superiority of FC over TAF. In the TS, related ocular adverse events (AEs) were more frequent for patients treated with FC compared to TIM (16.8% versus 6.4%), whereas related non-ocular AEs were more frequent with TIM compared to FC (2.1% versus 0.0%). In the PS, AEs were similarly distributed between FC and TAF. The frequency of conjunctival hyperemia of FC was low (6.4%).ConclusionThe preservative-free fixed combination of tafluprost and timolol provided a substantial and significant IOP reduction in both strata. The IOP reduction was superior to both tafluprost 0.0015% and timolol 0.5% when given as monotherapies. Overall, the study treatments were safe and well tolerated.FundingSanten Oy, Tampere, Finland.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0163-3) contains supplementary material, which is available to authorized users.

Tafluprost/Timolol: A Review in Open-Angle Glaucoma or Ocular Hypertension

“…4.1) or concomitant therapy with preservative-free tafluprost plus preservativefree timolol (Sect. 4.2) in adults with open-angle glaucoma or ocular hypertension [16,17]. Both studies used a double-blind, double-dummy design and enrolled patients aged C18 years with either open-angle glaucoma (primary openangle, pseudoexfoliative or pigmentary glaucoma) or ocular hypertension in at least one eye and a best corrected visual acuity no worse than ?0.6 logarithm of the minimal angle of resolution in both eyes.…”

“…Both studies used a double-blind, double-dummy design and enrolled patients aged C18 years with either open-angle glaucoma (primary openangle, pseudoexfoliative or pigmentary glaucoma) or ocular hypertension in at least one eye and a best corrected visual acuity no worse than ?0.6 logarithm of the minimal angle of resolution in both eyes. Key exclusion criteria included anticipated progression during the study period, advanced visual field defects in either eye, prior ocular surgery [including intraocular laser procedures within 6 months of screening in the study eye(s)], risk for angle closure, and the use of contact lenses [16,17].…”

“…Patients were required to have previously received therapy with either a prostaglandin analogue or timolol 0.5 % and to have an IOP in either treated eye at screening of C20 mmHg (with a prostaglandin analogue) or C22 mmHg (with timolol) [16]. Patients were stratified by previous therapy and underwent a 2-week nonblind run-in period with preservative-free tafluprost 0.0015 % once daily (for patients previously receiving a prostaglandin analogue) [prostaglandin analogue stratum] or preservative-free timolol 0.5 % twice daily (for patients previously receiving timolol 0.5 %) [timolol stratum] followed by a C4-week washout period.…”

“…Those with an increase of C2 mmHg in average diurnal IOP (measured at 8 a.m., 10 a.m., 4 p.m. and 8 p.m.) from the end of the run-in period to the end of the washout period (i.e. baseline) were randomized to receive tafluprost/timolol once daily (n = 188) or preservative-free tafluprost 0.0015 % once daily (n = 187) [prostaglandin analogue stratum] or tafluprost/timolol once daily (n = 95) or preservative-free timolol 0.5 % twice daily (n = 94) [timolol stratum] for 6 months [16].…”

Taflotan, the first preservative-free prostaglandin F2α analogue: treatment advantages in primary open-angle glaucoma patients

“…В РФ на сегодняшний день в распоряже-нии практического офтальмолога имеется всего три гипотензивных препарата без консерванта: Тимолол-ПОС® в системе COMOD ® , Ксонеф ® БК (бетаксолол в монодозах) и единственный ана-лог простагландина-F2α -Тафлотан ® . В декаб-ре 2015 года зарегистрирован комбинированный гипотензивный препарат Таптиком ® (тафлупрост с тимололом без консерванта), получивший поло-жительные отзывы зарубежных и отечественных специалистов [32]. Его появление в аптечной сети ожидается в ближайшее время.…”