Pharmacokinetics, Efficacy, and Safety of the Preservative-free Fixed Combination of Tafluprost 0.0015 % and Timolol 0.5 % in Healthy Volunteers: A Phase I Comparison vs. the Corresponding Preservative-free Monotherapies

Ikäheimo, Kirsi; Mannermaa, Eliisa; Ropo, Auli

doi:10.1007/s40262-015-0331-x

Cited by 18 publications

(13 citation statements)

References 39 publications

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“…Time to timolol C max was 15.0 and 22.5 min following a single dose and 37.5 and 30.0 min following multiple doses of tafluprost/timolol and timolol alone, respectively, with quantifiable timolol concentrations present 12-h post dose on days 1 and 8. Of note, as expected, timolol concentrations pre-dose on day 8 were significantly higher in the timolol alone group than the tafluprost/timolol group (234.7 vs. 37.5 pg/mL; p \ 0.001), likely reflecting the once-daily administration of timolol as part of combination therapy versus twicedaily administration as monotherapy [7].…”

Section: Pharmacokinetic Properties Of Tafluprost/ Timololsupporting

confidence: 67%

“…When used in combination, they provide an additional IOP-lowering effect compared with monotherapy with the individual components [6]. For instance, in 14 healthy volunteers participating in a randomized, three-period crossover study, preservative-free tafluprost/timolol once daily, preservative-free tafluprost 0.0015 % once daily and preservative-free timolol 0.5 % twice daily (each administered for 8 days) all demonstrated an IOP-lowering effect, with a significant (p \ 0.05) between-group difference (tafluprost/timolol vs. both monotherapies) in mean IOP over both eyes observed 2 h after dosing on day 8 [7]. Tafluprost is a fluorinated analogue of prostaglandin F 2a , which is an agonist of the human prostaglandin F (FP) receptor [6,8].…”

Section: Pharmacodynamic Properties Of Tafluprost/ Timololmentioning

confidence: 99%

“…In vitro, it is highly bound (99 % at 500 ng/ ml tafluprost acid) to human serum albumin [6]. Preservative-free tafluprost/timolol demonstrated generally similar systemic pharmacokinetic parameters to its individual components in healthy volunteers [7]. Following both single (day 1) and multiple (day 8) doses, there was no significant difference between tafluprost/timolol and preservative-free tafluprost 0.0015 % once daily in mean area under the plasma concentration-time curve (from time 0 to the last quantifiable timepoint) [AUC last ] and mean maximum plasma concentration (C max ) values for tafluprost acid.…”

Section: Pharmacokinetic Properties Of Tafluprost/ Timololmentioning

confidence: 99%

“…Cytochrome P450 (CYP) is not involved in the metabolism of tafluprost acid [6]. The elimination half-life (t ) of tafluprost acid could not be calculated in healthy volunteers as concentrations fell below the lower limit of quantification (\10 pg/mL) 30 min post dose [7]. Timolol is extensively metabolized in the liver (predominately by CYP2D6) to inactive metabolites, which are excreted primarily through the kidneys [6].…”

Section: Pharmacokinetic Properties Of Tafluprost/ Timololmentioning

confidence: 99%

“…Timolol is extensively metabolized in the liver (predominately by CYP2D6) to inactive metabolites, which are excreted primarily through the kidneys [6]. The t of timolol from human plasma is 4 h [7].…”

Section: Pharmacokinetic Properties Of Tafluprost/ Timololmentioning

confidence: 99%

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

Hoy

2015

Drugs

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A once-daily preservative-free fixed combination ophthalmic solution containing tafluprost 0.0015 % and timolol 0.5 % (hereafter referred to as tafluprost/timolol) [Taptiqom(®)] has been developed to lower intraocular pressure (IOP) whilst avoiding damage to the ocular surface associated with preservatives such as benzalkonium chloride. Tafluprost/timolol is available in various EU countries for the reduction of IOP in adults with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical monotherapy with β-adrenergic receptor antagonists or prostaglandin analogues and require a combination therapy, and who would benefit from preservative-free eye drops. In two multinational, phase III studies, tafluprost/timolol was superior to monotherapy with either preservative-free tafluprost 0.0015 % once daily or preservative-free timolol 0.5 % twice daily, and noninferior to concomitant therapy with preservative-free tafluprost 0.0015 % once daily plus preservative-free timolol 0.5 % twice daily in lowering IOP in adults with open-angle glaucoma or ocular hypertension. Tafluprost/timolol was well tolerated in these studies, with a tolerability profile consistent with that of its individual components and with no new adverse reactions observed. Thus, preservative-free fixed combination tafluprost/timolol is an effective treatment option for the reduction of IOP in adults with open-angle glaucoma or ocular hypertension, providing a useful alternative for those patients who would benefit from preservative-free eye drops.

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Section: Pharmacokinetic Properties Of Tafluprost/ Timololsupporting

confidence: 67%

Section: Pharmacodynamic Properties Of Tafluprost/ Timololmentioning

confidence: 99%

Section: Pharmacokinetic Properties Of Tafluprost/ Timololmentioning

confidence: 99%

Section: Pharmacokinetic Properties Of Tafluprost/ Timololmentioning

confidence: 99%

Section: Pharmacokinetic Properties Of Tafluprost/ Timololmentioning

confidence: 99%

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

Hoy

2015

Drugs

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Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: The VISIONARY Study

et al. 2020

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Introduction: A non-interventional, multicenter, European, prospective evaluation of the effectiveness, tolerability, and safety of a topical preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) demonstrating insufficient response to topical beta-receptor blockers or prostaglandin analogue (PGA) monotherapy. Methods: Mean intraocular pressure (IOP) change from baseline was measured at study visits following a switch to PF tafluprost/timolol FC. Primary endpoint was absolute mean IOP change at month 6. Change from baseline concerning ocular signs and symptoms was also explored.Results: Analyses included 577 patients (59.6% female). Mean age (SD) was 67.8 (11.67) years. Mean (SD) IOP reduction from baseline was significant at all study visits; 5.4 (3.76) mmHg (23.7%) at week 4, 5.9 (3.90) mmHg (25.6%) at week 12, and 5.7 (4.11) mmHg (24.9%) at month 6 (p \ 0.0001 for all visits). At month 6, 69.2%, 53.6%, 40.0%, and 25.8% were responders based on C 20%, C 25%, C 30%, and C 35% cutoff values for mean IOP, respectively. Significant reductions were observed concerning corneal fluorescein staining (p \ 0.0001), dry eye symptoms, irritation, itching, and foreign body sensation (p \ 0.001 for each parameter). Conjunctival hyperemia was significantly reduced at all study visits (p \ 0.0001 at each visit). Overall, 69 treatment-related adverse events (AEs) were reported, one of which was serious (status asthmaticus). Most AEs were mild to moderate in severity, and the majority had resolved or were resolving at the end of the study period. Conclusion: In clinical practice, PF tafluprost/timolol FC provided statistically and clinically significant IOP reductions in patients with OAG and OHT insufficiently controlled on or intolerant to PGA or beta-receptor blocker monotherapy. The full IOP reduction appeared at week 4 and was maintained over the 6-month study period. Key symptoms of ocular surface health improved. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.The members of The VISIONARY Study Group are listed in Acknowledgements. Key Summary PointsWhy carry out this study?Prostaglandin analogue (PGA) and betareceptor blocker combination therapies are among the most extensively used intraocular pressure (IOP)-lowering treatments in glaucoma care. Fixed-dose combinations simplify the treatment regimen and reduce the number of daily instillations, compared with administration of the corresponding concomitant medications, and preservative-free formulations are generally considered to offer improved tolerability.The VISIONARY study aimed to provide real-world data concerning the treatment effectiveness of the preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in people with open-angle glaucoma (OAG) and ocular hypertension (OHT) who demonstrated an insufficient response ...

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Switching to Preservative-Free Tafluprost/Timolol Fixed-Dose Combination in the Treatment of Open-Angle Glaucoma or Ocular Hypertension: Subanalysis of Data from the VISIONARY Study According to Baseline Monotherapy Treatment

Oddone

Fassari

Faschinger³

et al. 2022

Adv Ther

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Introduction The VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% (PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy. Methods A European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6. Results The subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 ( p < 0.001). Mean (SD) IOP change at Month 6 was 6.6 (4.16), 6.3 (4.39), 5.6 (3.67), 4.9 (2.97), 4.6 (4.39), and 4.7 (3.64) mmHg for prior beta-blocker, preserved latanoprost, PF-latanoprost, tafluprost, bimatoprost, and travoprost subgroups, respectively. The largest IOP change was observed in the preserved latanoprost subgroup for each of the ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% IOP reduction categories at Month 6, demonstrating respective reductions of 8.06, 9.20, 10.64, and 11.55 mmHg. CFS was significantly reduced at Month 6 in the prior bimatoprost subgroup ( p = 0.0013). Conjunctival hyperemia severity was significantly reduced at each study visit for prior preserved latanoprost users ( p < 0.001). Conclusion PF tafluprost/timolol FC therapy provided statistically and clinically significant IOP reductions from Week 4 over the total 6-month period, in patients with OAG/OHT, regardless of the type of prior PGA or beta-blocker monotherapy used. Conjunctival hyperemia severity and CFS decreased significantly in prior bimatoprost and preserved latanoprost users, respectively. Clinical Study Number European Union electronic Register of Post-Authorization Studies (EU PAS) register number: EUPAS22204. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02166-6.

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Pharmacokinetics, Efficacy, and Safety of the Preservative-free Fixed Combination of Tafluprost 0.0015 % and Timolol 0.5 % in Healthy Volunteers: A Phase I Comparison vs. the Corresponding Preservative-free Monotherapies

Abstract: PF FDC demonstrated good IOP-lowering efficacy and displayed similar pharmacokinetic characteristics to the monotherapy agents. Exposure to timolol was reduced via the halved dosing.

Cited by 18 publications

References 39 publications

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

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

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: The VISIONARY Study

Switching to Preservative-Free Tafluprost/Timolol Fixed-Dose Combination in the Treatment of Open-Angle Glaucoma or Ocular Hypertension: Subanalysis of Data from the VISIONARY Study According to Baseline Monotherapy Treatment

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