Brimonidine-purite 0.1% versus brimonidine-purite 0.15% twice daily in glaucoma or ocular hypertension: a 12-month randomized trial*

ABSTRACT

Objective: To compare the safety and intraocular pressure (IOP)-lowering effects of brimonidine-purite^? 0.1% with the marketed formulation of brimonidine-purite 0.15% (Alphagan P^§ 0.15%) when used twice daily (BID) by patients with glaucoma or ocular hypertension previously treated with brimonidine-purite 0.15% for at least 6 weeks.

Methods: In a 12-month, randomized, double-masked, multicenter, parallel group, non-inferiority study, patients with glaucoma or ocular hypertension who were treated with brimonidine-purite 0.15% BID were randomly assigned to continue brimonidine-purite 0.15% (n = 102) or to administer brimonidine-purite 0.1% (n = 105) BID for 12 months. IOP was measured at approximately 8 a.m. (hour 0) and 10 a.m. (hour 2).

Main outcome measures: Mean change from baseline IOP and adverse events.

Results: Demographics and baseline characteristics were similar between treatment groups. Treated-baseline mean IOPs at both timepoints were similar between groups (p ≥ 0.606). Brimonidine-purite 0.1% provided IOP-lowering that was non-inferior to brimonidine-purite 0.15% at each of the 12 follow-up timepoints, and there were no statistically significant between-group differences at any timepoint. The most commonly reported adverse event was conjunctival hyperemia (13.5% for brimonidine-purite 0.1%; 10.8% for brimonidine-purite 0.15%). No significant differences in the incidence of adverse events were noted between the two formulations.

Conclusions: Brimonidine-purite 0.1% BID is as effective as brimonidine-purite 0.15% BID in lowering IOP in patients with glaucoma or ocular hypertension who were previously treated with brimonidine-purite 0.15%, and both formulations are well tolerated. Limitations of the study include enrollment of only patients who were already on treatment with brimonidine-purite 0.15%. The 0.1% formulation of brimonidine-purite allows for decreased exposure to brimonidine while providing an IOP-lowering effect comparable to that of the 0.15% formulation. Clinical trial registered at clinicaltrials.gov; identifier: NCT00168363.     

Efficacy and safety of brimonidine and dorzolamide for intraocular pressure lowering in glaucoma and ocular hypertension

ABSTRACT

Background: Brimonidine and dorzolamide are intraocular pressure (IOP)-lowering medications most commonly used in second-line treatment of glaucoma and ocular hypertension.

Scope: An evidence-based review of comparative clinical trials of brimonidine and dorzolamide was undertaken to determine the relative efficacy and safety of these drugs in reducing IOP. Using the keywords ‘brimonidine’ and ‘dorzolamide’, all articles describing such trials from September 1966 to July 2007 were found in MEDLINE and EMBASE.

Findings: In all identified studies, brimonidine and dorzolamide were both found to provide significant IOP reduction from treated or untreated baseline levels. Results of eight trials reported to date indicate that brimonidine produced either a lower treated IOP or greater pressure reduction from baseline than dorzolamide at one or more measured timepoints, and provided comparable IOP lowering over all other measurements. Differences between the IOP reductions provided by brimonidine and dorzolamide were more pronounced when the medications were used adjunctively with other classes of drugs. Six other trials showed similar efficacy, and one additional monotherapy study showed lower IOP with dorzolamide treatment. Ocular burning was noted with dorzolamide more than any other adverse event with either drug. Trials ranged widely in duration of therapy and the time of day IOP measurements were taken, and many were too small for sufficient statistical power.

Conclusion: Brimonidine and dorzolamide are both efficacious and reasonably well tolerated. Possible overall distinctions in efficacy were obscured by differences in study designs and treatment regimens, but adjunctive therapy with brimonidine may reduce IOP as effectively or more effectively than adjunctive or fixed combination dorzolamide therapy. In certain patients with glaucoma and ocular hypertension brimonidine may be a better choice than dorzolamide for second-line treatment.     

Intraocular pressure lowering effect of brinzolamide 1.0% as adjunctive therapy to latanoprost 0.005% in patients with open angle glaucoma or ocular hypertension: an uncontrolled, open-label study

PURPOSE: A prospective study was conducted to evaluate the intraocular pressure (IOP) lowering effect of brinzolamide 1.0% ophthalmic suspension as an adjunctive therapy with latanoprost 0.005% ophthalmic solution in patients with open angle glaucoma or ocular hypertension. PATIENTS AND METHODS: Fourteen patients with open angle glaucoma (OAG) or ocular hypertension (OH) who had been using latanoprost 0.005% for more than 6 months were initiated on adjunctive brinzolamide therapy. The IOP values at 1 month, 2 months, and 3 months were compared with those measured immediately before adding brinzolamide to the regimen (baseline). The incidence of adverse events such as conjunctival hyperemia and corneal epithelial defect were also examined. RESULTS: The baseline IOP was 21.1 +/- 4.8 mmHg (mean +/- standard deviation). After 1 month, 2 months, and 3 months of therapy IOP was 16.9 +/- 4.5 mmHg, 16.6 +/- 4.0 mmHg, and 15.9 +/- 3.1 mmHg, respectively, showing significant reductions in IOP at all the measuring time-points during the study compared with the baseline value (p < 0.01). Conjunctival hyperemia developed in one patient after 1 month and in another after 2 months; however, both were mild, and therapy was continued. Corneal epithelium defect was observed in 3 patients. One of them had mild defect before brinzolamide was added to the regimen. Increase of eye discharge was seen in one patient. No serious side effects were otherwise observed. CONCLUSION: The addition of brinzolamide to a latanoprost 0.005% regimen may further lower intraocular pressure in patients with open angle glaucoma or ocular hypertension.     

IOP-lowering efficacy and tolerability of preservative-free tafluprost 0.0015% among patients with ocular hypertension or glaucoma

Abstract

Objective:

Tafluprost, the first preservative-free prostaglandin analogue for topical ophthalmic use to lower IOP, was introduced in Germany in 2008. After the approval for ophthalmic use, an open-label, multicentre, observational study was conducted between October 2008 and April 2009. Major objectives of this study were to evaluate the real world efficacy, local tolerability and safety of this first in class preservative-free prostaglandin preparation in patients with ocular hypertension and glaucoma.     

0.15%阿法根P治疗开角型青光眼或高眼压症患者临床应用观察

目的 分析比较0.15%阿法根P(0.15%酒石酸溴莫尼定滴眼液)和阿法根(0.2%酒石酸溴莫尼定滴眼液)治疗开角型青光眼或高眼压症患者的应用临床效果.方法 随机分组,观察组32例患者(0.15%阿法根P,Bid)和对照组35例(阿法根,bid),随访1年.结果 0.15%阿法根P的降眼压疗效与阿法根相同,而0.15%阿法根P的安全性和耐受性优于阿法根.结论 0.15%阿法根P在临床中应用安全有效,优于阿法根.     

Intraocular pressure reduction with travoprost/timolol fixed combination,with and without adjunctive brinzolamide,in glaucoma

ABSTRACT

Objective: To investigate if combined intraocular pressure (IOP)-lowering medication with travoprost/timolol fixed combination and a carbonic anhydrase inhibitor, brinzolamide, is superior to both travoprost monotherapy and travoprost/timolol fixed-combination therapy in primary open-angle glaucoma and ocular hypertension.

Methods: Following a 4-week wash-out period and using 4-week long treatment periods, 20 primary open-angle glaucoma or ocular hypertension patients were treated with evening travoprost 0.004?%?, then switched to evening travoprost 0.004?%?/timolol 0.5?%?fixed combination, and finally the treatment was combined with adjunctive twice-daily brinzolamide 1?%?ophthalmic suspension. Both eyes were treated, but only one eye per patient (the eye with the higher mean diurnal IOP at baseline), was evaluated. IOP was measured at 8 a.m., 12 noon and 4 p.m. at baseline and at the end of each treatment period.

Results: Mean diurnal IOP (mean (SD)) at baseline was 28.5 (7.3) mmHg which decreased to 22.3 (6.3) mmHg on travoprost, 19.2 (3.4) mmHg on travoprost/timolol fixed combination and 17.3 (3.4) mmHg when the brinzolamide was added to the travoprost/timolol combination (ANOVA, contrast test, p?<?0.003 for all comparisons). The individual time point IOP values showed similar and significant stepwise differences.

Conclusion: Adjunctive brinzolamide medication provided further IOP decrease in patients receiving evening-dosed travoprost/timolol fixed combination. The travoprost/timolol fixed combination was significantly more effective in IOP reduction than travoprost monotherapy, which by itself induced a significant IOP decrease compared to the untreated baseline value. The results of this open label study suggest that combined therapy with travoprost/timolol fixed combination and brinzolamide is clinically useful for IOP-lowering in primary open-angle glaucoma and ocular hypertension.     

Comparison of the efficacy and safety of travoprost with a fixed-combination of dorzolamide and timolol in patients with open-angle glaucoma or ocular hypertension

ABSTRACT

Purpose: The purpose of this study was to compare travoprost (TRAV; travoprost 0.004%) and the fixed-combination of dorzolamide/timolol (DTFC; dorzolamide 2.0%/timolol maleate 0.5%) ophthalmic solutions for reducing intraocular pressure (IOP) in patients with primary open-angle glaucoma (OAG) or ocular hypertension (OHT).

Methods: This was a randomized single masked, study with parallel controls. The TRAV group (n = 29) dosed once daily at 9:00 PM while the DTFC group (n = 27) dosed twice daily at 9:00 AM and 9:00 PM. IOP was measured at baseline, and following 3 weeks and 6 weeks of treatment at 8:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM.

Results: Mean average IOP reductions from baseline during the course of the day were 7.5 (32.7%) and 7.1 (30.7%)?mmHg for TRAV and 4.8 (23.1%) and 4.5 (21.7%)?mmHg for DTFC at 3 weeks and 6 weeks, respectively. The greater IOP reduction for patients receiving TRAV was statistically significant at both the 3 and 6 week visits when averaged across all four time points (?p < 0.01). The two products were well-tolerated over the course of the 6 week study. Some factors such as taste perversion were reported more often in the DTFC group.

Conclusions: Travoprost monotherapy provided better efficacy in terms of IOP reduction and per-centage of IOP reduction compared to dorzolamide 2.0%/timolol maleate 0.5% fixed combination.     

Preservative-free versus preserved latanoprost eye drops in patients with open-angle glaucoma or ocular hypertension

Objective: This study compared the efficacy, safety, and pharmacokinetics of a preservative-free latanoprost formulation to an established, benzalkonium chloride (BAK) containing formulation for the treatment of open-angle glaucoma or ocular hypertension.

Methods: This was a phase II, randomized, cross-over, investigator-masked, multi-center, pilot study (NCT01494753). A total of 30 untreated adult patients (aged ≥18 years) with primary open angle glaucoma, pseudo-exfoliative glaucoma, pigmentary glaucoma, or ocular hypertension received either preservative-free or preserved latanoprost once daily in both eyes for 6 weeks, before crossing over to receive the other treatment. Efficacy (intraocular pressure [IOP] at 8 am, midday, 4?pm and 8?pm, and global efficacy assessment by investigator), safety (adverse events, ocular symptoms and global tolerance, slit lamp examination, funduscopy, visual field examination, visual acuity, and heart rate), and pharmacokinetics were assessed at Days 0, 42, and 84.

Results: Both treatments resulted in a reduction in IOP that was similar for the preservative-free and the preserved formulation at all time points. Similarly, the overall diurnal reduction was similar in both groups (6.3?mmHg [27.9% reduction] and 6.4?mmHg [28.1% reduction] for preserved and preservative-free latanoprost, respectively). There were no differences in global efficacy assessment or in the safety and tolerance of each treatment. Systemic concentrations of latanoprost were very low; AUC_0–30 and C_max were lower and t_max was longer for preservative-free latanoprost.

Conclusions: Preservative-free latanoprost showed similar efficacy at all time points compared to BAK preservative containing formulation, with no difference in tolerance, allowing progression to phase III clinical development.     

Comparison of morning versus evening dosing and 24-h post-dose efficacy of travoprost compared with latanoprost in patients with open-angle glaucoma

ABSTRACT

Objective: To compare the IOP-lowering efficacy of a.m.-dosed travoprost and latanoprost at 24-h post-dose.

Research design and methods: Open-angle glaucoma patients not naïve to prostaglandin therapy and currently controlled on p.m.-dosed (2100) latanoprost (n?=?21) or travoprost (n?=?30) had baseline IOPs measured at 0900. In a randomized, single-masked, crossover design, patients received travoprost (Travatan) or latanoprost (Xalatan) at 0900 for 4?weeks, then were crossed over to receive the second prostaglandin for another 4?weeks. Treatment IOP was measured at 0900 prior to morning dose at both 4 and 8?week visits. Patient dosing preference (a.m./p.m.) was surveyed on exit.

Main outcome measure: Intraocular pressure (IOP).

Results: The mean IOP in the first period when all patients were dosed in the evening was assessed 12?h after dosing at 09:00 and it was similar in the two treatment groups (mean?±?standard deviation: 17.9?±?2.7?mmHg for travoprost versus 17.7?±?2.5?mmHg for latanoprost, p?=?0.812). In the a.m.-dosing crossover comparison, the 24-h post-dose IOP was significantly lower (?p?<?0.001) on travoprost (16.9?±?3.1?mmHg) compared to latanoprost (18.6?±?3.3?mmHg). In the exit survey, 51% of patients preferred a.m.-dosing.

Conclusions: a.m.-dosed travoprost is superior to a.m.-dosed latanoprost by 1.7?mmHg at 24-h post-dose.     

Ocular hypotensive efficacy and safety of brinzolamide ophthalmic suspension 1% added to travoprost ophthalmic solution 0.004% therapy in patients with open-angle glaucoma or ocular hypertension

OBJECTIVE: The primary objective of this study was to determine if combined travoprost ophthalmic solution 0.004% and brinzolamide ophthalmic suspension 1% therapy is superior in lowering intraocular pressure (IOP) compared to travoprost monotherapy for patients with open angle glaucoma or ocular hypertension. The secondary objective was to measure the percentage of patients achieving IOP levels of 18 mmHg or less. STUDY DESIGN AND METHODS: Single arm, open-label. PARTICIPANTS: eighty-two patients with inadequate IOP control with travoprost monotherapy. INTERVENTION: the addition of brinzolamide ophthalmic suspension 1% twice daily. MAIN OUTCOME MEASURES: The primary endpoint was mean IOP reduction from baseline at 4 and 12 weeks. The percentage of patients who achieved IOP values 相似文献   

Latanoprostene bunod ophthalmic solution 0.024% for IOP lowering in glaucoma and ocular hypertension

Introduction: Intraocular pressure (IOP)-lowering has been demonstrated to slow the progression or onset of visual field loss in open-angle glaucoma (OAG) or ocular hypertension (OHT). Pharmacological lowering of IOP is the most common initial intervention in patients with OAG or OHT, however, many patients will require more than one therapy to achieve target IOP. Latanoprostene bunod is a novel nitric oxide (NO)-donating prostaglandin F2α analog for the reduction of IOP.

Areas covered: Current knowledge concerning the mechanism of action of latanoprostene bunod is presented. Additionally, clinical safety and efficacy data from published Phase 1 (KRONUS), Phase 2 (VOYAGER, CONSTELLATION) and Phase 3 (APOLLO, LUNAR, JUPITER) studies are reviewed.

Expert opinion: Latanoprostene bunod is a dual mechanism, dual pathway molecule, consisting of latanoprost acid, which is known to enhance uveoscleral (unconventional) outflow by upregulating matrix metalloproteinase expression and remodeling of the ciliary muscle’s extracellular matrix, linked to an NO-donating moiety, which enhances trabecular meshwork/Schlemm’s canal (conventional) outflow by inducing cytoskeletal relaxation via the soluble guanylyl cyclase-cyclic guanosine monophosphate (sGC-cGMP) signaling pathway. Latanoprostene bunod 0.024% solution applied topically once daily appears more effective in reducing IOP in OHT and OAG subjects than either latanoprost or timolol, with a side effect profile similar to that of latanoprost.     

Safety of unoprostone isopropyl as mono- or adjunctive therapy in patients with primary open-angle glaucoma or ocular hypertension.

This review summarises the safety of unoprostone isopropyl (both at the 0.12 and 0.15% concentrations) instilled twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). For unoprostone 0.15%, combined data from two 12-month comparative monotherapy studies are reported, as well as data from three adjunctive therapy studies and two special population studies. With unoprostone monotherapy, most adverse events were mild or moderate and transient in nature. Less than 7% of unoprostone-treated patients discontinued therapy due to an adverse event. The most common adverse events associated with unoprostone were burning/stinging, burning/stinging directly upon drug instillation, ocular itching, and conjunctival hyperaemia. Unoprostone had no clinically notable effects on vital signs, laboratory profiles, or comprehensive ophthalmic examinations. One of 659 unoprostone 0.15%-treated patients had a change in iris colour after 12 months of monotherapy. Except for a higher incidence of burning/stinging and burning/stinging upon instillation, unoprostone was comparable to timolol 0.5% twice daily and betaxolol 0.5% twice daily. No safety concerns were raised with use of unoprostone as adjunctive therapy. Unoprostone had no significant effect on exercise-induced heart rate in healthy subjects or on pulmonary function in patients with mild-to-moderate asthma. The safety profile of unoprostone 0.15% was consistent with published information on the 0.12% formulation. In conclusion, unoprostone has an excellent safety profile in patients with POAG or OH.     

Evaluation of eye drop administration technique in patients with glaucoma or ocular hypertension

Abstract

Objective:

To evaluate eye drop administration by patients at multiple visits in the setting of a randomized controlled trial.     

Estimated comparative costs of achieving a 20% reduction in intraocular pressure with bimatoprost or latanoprost in patients with glaucoma or ocular hypertension

BACKGROUND: Although the probability of treatment success should be the primary factor guiding the choice of an intraocular pressure (IOP)-lowering medication, treatment cost is also important to physicians, patients and third-party payers. The objective of the present study was to compare the cost effectiveness of bimatoprost with that of latanoprost in the treatment of glaucoma and ocular hypertension. METHODS: Estimated yearly costs and cost per treatment success for bimatoprost ophthalmic solution 0.03% once daily (Lumigan), Allergan, Inc., Irvine, CA, USA) were compared with those for latanoprost ophthalmic solution 0.005% once daily (Xalatan), Pfizer, Inc., New York, NY, USA). The pharmacoeconomic model was based on medical resource costs and the percentage of patients achieving > or =20% decrease in IOP from baseline at 8:00 am, 12:00 pm and 4:00 pm after 6 months of treatment (clinical success rate). Calculations were also made using the average success rate throughout the day and the average success rate minus the percentage of patients who withdrew from treatment as a result of adverse events. RESULTS: After 6 months of treatment, the clinical success rates were significantly higher with bimatoprost than with latanoprost (p < or = 0.003). The average expected yearly cost per patient was similar for bimatoprost (US1151 dollars) and latanoprost (US1193 dollars). The cost per treatment success, however, averaged US568 dollars less with bimatoprost (US1501 dollars/success) than with latanoprost (US2069 dollars/success). This was true even when the percentage of patients who withdrew from treatment as a result of adverse events was subtracted from the clinical success rate. CONCLUSION: The greater efficacy of bimatoprost resulted in a lower cost per treatment success than was seen with latanoprost. This remained true even when responder rates were adjusted by subtracting the percentage of patients who withdrew from treatment as a result of adverse events.     

Efficacy and safety of tafluprost 0.0015% and timolol maleate 0.5% fixed combination in patients with ocular hypertension or open-angle glaucoma

Introduction: Lowering intraocular pressure (IOP) is at present the only therapeutic approach to the treatment of glaucoma proven to be successful. The choice of therapy must take into account efficacy, tolerability, safety, quality of life, adherence and cost. Monotherapy fails to achieve a satisfactory IOP reduction in 40 – 75% of glaucoma patients after > 2 years of therapy. So far, three prostaglandin/timolol maleate 0.5% fixed combinations (FCs) are available.

Areas covered: This review provides a background on the tafluprost–timolol FC (TTFC, Santen Oy) and its individual compounds. It summarizes the data on efficacy and safety, including comparative data with prostaglandin/timolol FCs already available.

Expert opinion: Tafluprost is a preservative-free prostaglandin analog with a similar IOP efficacy when compared with other prostaglandin analogs. However, its improved adverse effect profile seems to be beneficial in patients sensitive to preservatives. The preservative-free TTFC has no market authorization yet. Only one Phase III trial was published so far, but results are promising in terms of efficacy, tolerability and safety. It is likely that the TTFC will play a role in the treatment of open-angle glaucoma and ocular hypertension.     

Changes in intraocular pressure following a switch from latanoprost monotherapy to latanoprost/timolol fixed combination therapy in patients with primary open-angle glaucoma or ocular hypertension: results from a clinical practice database

ABSTRACT

Aims: To assess the incremental change in intraocular pressure (IOP) levels in patients with primary open-angle glaucoma or ocular hypertension, insufficiently treated with topical ocular hypotensive monotherapy or combination therapy and changed to the latanoprost/timolol fixed-combination therapy (LTFC).

Methods: The glaucoma database of the Glasgow Royal Infirmary was reviewed retrospectively to identify patients ≥?18 years of age with primary open-angle glaucoma or ocular hypertension in at least one eye who had been switched to LTFC from a previous monotherapy or combination therapy. Ninety patients were identified, and 59 (66%) had changed to LTFC from latanoprost monotherapy (LM). The analysis focused on this subgroup because few patients were changed from any other single therapy. At least one documented patient visit following the change to LTFC was required. The within-subject difference in IOP levels (IOP on LM–IOP on LTFC) was calculated for each case, and the statistical significance of the mean change in IOP was analysed using a 2-sided Student's paired t-test with a 0.05 α level.

Results: The mean decrease in IOP after changing to LTFC from LM was 2.6?mmHg (95% confidence interval?=?1.6, 3.6), from 21.4 (SD?=?3.5) mmHg to 18.8 (SD?=?4.2) mmHg (p?=?0.002).

Conclusions: LTFC provides significant incremental IOP reduction in patients with primary open-angle glaucoma or ocular hypertension who require additional IOP reduction following treatment with LM.     

Switching from concomitant latanoprost 0.005% and timolol 0.5% to a fixed combination of travoprost 0.004%/timolol 0.5% in patients with primary open-angle glaucoma and ocular hypertension: a 6-month,multicenter, cohort study

Purpose: To assess the usefulness and tolerability of systematically switching glaucoma patients from latanoprost 0.005% and timolol 0.5% (Lat + Tim) to a fixed combination of travoprost 0.004%/timolol 0.5% (TTFC), and to record the effects of this switch on tear-film break-up time (TBUT). Main outcome measures: Intraocular pressure (IOP) reduction, patients reaching IOP < 18 mmHg; the rate of discontinuation; TBUT; and the onset of adverse events (AEs). Methods: Multicenter, observational cohort, 6-month study: 309 patients on concomitant Lat + Tim were switched to TTFC (evening dosage). IOP, TBUT, and AEs were recorded at baseline and after 1 and 6 months. Results: IOP was significantly decreased (from 18.3 ± 2.9 to 16.6 ± 2.7 mmHg) after substitution (p < 0.0001). Many patients (82%) reached an IOP < 18 mmHg (p < 0.0001). TBUT improved significantly (from 8.4 ± 3.6 to 9.2 ± 3.8 s, p < 0.0001). A few patients reported AEs (8.7%), which caused discontinuation in a low percentage (4.5%). Conclusion: TTFC appeared useful in this selected population. In this study, patients who underwent a regimen modification to TTFC obtained further reduction in IOP with a lower exposition to preservative toxicity. The low discontinuation rate at 6 months indicates a good tolerability profile.