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Comparison of the Safety and Efficacy between Preserved and Preservative-Free Latanoprost and Preservative-Free Tafluprost.

ABSTRACT: In this study, we investigated the effect of preservative-free (PF) 0.0015% tafluprost (TA), to the preservative containing (PC) and the PF 0.005% latanoprost (LA) in Korean subjects. This study was conducted as a multi-center, randomized, investigator-blind, active controlled, parallel-group, clinical trial in adult patients (≥19 years) with open-angle glaucoma (OAG) and ocular hypertension (OHT). After a washout period, patients with an IOP between 15 and 35 mmHg were enrolled and evaluated the efficacy, safety, and compliance at 4, 8 and 12 weeks after the first administration. A total of 137 OAG and OHT patients were randomized. Statistically significant reductions in IOP were observed in all groups. Twelve weeks after each eye drop instillation, the mean IOP reduction was -4.59 ± 2.70 mmHg (-24.57 ± 13.49%) in the PC-LA group, -4.52 ± 2.17 mmHg (-24.41 ± 11.38%) in the PF-LA, and -3.14 ± 2.83 mmHg (-17.22 ± 14.57%) in the PF-TA group. The PF-LA showed significantly better responsiveness than did PF-TA. PF-LA was better tolerated than was PC-LA. There were no adverse events that led to cessation of eye drop use in any of the groups. In conclusion, IOP decreased similarly across the groups. PF-LA may provide a good choice for OAG patients with ocular surface diseases.

SUBMITTER: Kim JM

PROVIDER: S-EPMC8225154 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD). METHODS:Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period. RESULTS:Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001). CONCLUSIONS:In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy. TRIAL REGISTRATION:ClinicalTrials.gov (NCT02802137). FUNDING:Santen.

Project description: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.

Project description:To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity.The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1-30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated.The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4-8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24-30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24-30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs.Taf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC.

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Comparison of the Safety and Efficacy between Preserved and Preservative-Free Latanoprost and Preservative-Free Tafluprost.

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