To assess clinical antimicrobial efficacy results obtained with besifloxacin ophthalmic suspension, 0.6%, administered three times a day (TID) for 5 days, integrated across three clinical trials of ...bacterial conjunctivitis and to investigate any microbiological eradication failures.
Clinical microbiological eradication data from three randomized, double-masked, parallel group studies of patients with bacterial conjunctivitis (two vehicle controlled; one active controlled with moxifloxacin ophthalmic solution, 0.5%) were integrated. All bacterial samples isolated at baseline above the species-specific threshold value were subjected to antimicrobial susceptibility testing. Samples isolated at subsequent visits were subjected to susceptibility testing and pulsed-field gel electrophoresis (PFGE) to investigate the cause of eradication failures and the potential for drug resistance development.
Visit 2 (day 4 or 5) and visit 3 (day 8) overall microbiological eradication rates were 92.2% and 88.4% for besifloxacin ophthalmic suspension compared with 61.4% and 72.5% for vehicle and 91.6% and 85.7% for moxifloxacin ophthalmic solution. Visit 2 and visit 3 microbiological eradication rates for Gram-positive and Gram-negative isolates and for individual species were consistent with the overall eradication rates. The majority of observed eradication failures in any treatment group were due to the persistence of the pathogen isolated at baseline. Eradication failures in the besifloxacin treatment group were not associated with lower antimicrobial susceptibility at baseline. PFGE data showed that the majority of bacterial strains in eyes with eradication failures were identical to the strain isolated at baseline; these eradication failures were not associated with a lower antimicrobial susceptibility at the follow-up visit.
Treatment with besifloxacin ophthalmic suspension, 0.6%, administered TID for 5 days resulted in microbiological eradication rates that were ≥ 90% across the three clinical studies for the common pathogens of bacterial conjunctivitis. The few eradication failures were not due to fluoroquinolone resistance at baseline and/or resistance development during treatment.
Background: Besifloxacin is a novel fluoroquinolone, specifically a chloro-fluoroquinolone, with potent broad-spectrum bactericidal activity for the topical treatment of bacterial conjunctivitis. ...Objective: The objective of this report was to provide a comprehensive assessment of the safety and tolerability of besifloxacin ophthalmic suspension 0.6% across clinical and phase I safety studies. Methods: Data were drawn from two phase I safety studies in healthy adults, an open-label, phase II pharmacokinetic study of patients with bacterial conjunctivitis and from integrated data from three randomized, doublemasked, parallel-group, safety and efficacy studies of patients with bacterial conjunctivitis (two were vehicle controlled and one was active controlled with moxifloxacin ophthalmic solution 0.5%, as base). Safety assessments included changes in visual acuity, ocular assessments with ophthalmoscopy and biomicroscopy, and assessment of adverse events (AEs). Results: Safety data for besifloxacin ophthalmic suspension 0.6% were available for 1350 patients, including 1192 patients (1810 eyes) in the integrated analysis. Systemic exposure following topical administration of besifloxacin ophthalmic suspension 0.6% was negligible. No changes were seen in corneal endothelial cell density. In the integrated safety analysis of the three safety and efficacy studies, the most commonly reported ocular AEs in study eyes receiving besifloxacin ophthalmic suspension 0.6% were blurred vision (2.1%), eye pain (1.8%), eye irritation (1.4%), nonspecific conjunctivitis (1.2%) and eye pruritus (1.1%). Blurred vision, eye irritation and nonspecific conjunctivitis occurred in significantly fewer besifloxacin-treated patients than in vehicle-treated patients (p 0.05 less than or equal to). Headache (1.8%) was the most frequently reported non-ocular AE. Most AEs were mild in severity and there were no treatment-related serious AEs. Besifloxacin ophthalmic suspension 0.6% did not significantly affect visual acuity, biomicroscopy or ophthalmoscopy compared with vehicle or moxifloxacin. Conclusion: The results from this comprehensive data set of 1350 patients demonstrate that besifloxacin ophthalmic suspension 0.6% has a favourable safety profile and is well tolerated.
ABSTRACT
Objective: To compare the ocular comfort and tolerability of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T; Zylet*) with dexamethasone 0.1%/tobramycin 0.3% (DM/T; TobraDex†) in healthy ...volunteers.
*Zylet is a registered trademark of Bausch &Lomb, Inc., Tampa FL, USA
†TobraDex is a registered trademark of Alcon Laboratories, Inc., Fort Worth, TX, USA
Research design and methods: In this multicenter, randomized, double-masked, parallel-group study, healthy volunteers (n = 306) were randomized to receive LE/T or DM/T four times per day for 28 days. Subjects recorded subjective ratings for seven comfort/tolerability parameters using an electronic patient diary (EPD). The primary endpoint was the difference at week 4 from the ratings of an artificial tear at baseline in comfort/tolerability parameters between treatment groups, using a noninferiority paradigm.
Clinical trials registration: ClinicalTrials.gov, NCT 00532961.
Results: The 97.5% confidence intervals for the lower bound were within –10 for all of the seven comfort/tolerability parameters evaluated (pain, stinging/burning, irritation, itchiness, foreign-body sensation, dryness, and light sensitivity). Secondary analysis revealed small but significant within-treatment differences in pain favoring LE/T over tears and in light sensitivity favoring tears over DM/T (p < 0.01). Small between-treatment differences in the changes from baseline tear ratings to individual study visits favored LE/T for pain, stinging/burning, irritation, itchiness, foreign-body sensation, and light sensitivity at visit 4 (p ≤ 0.04); for pain, stinging/burning, and foreign-body sensation at visit 5 (p ≤ 0.03), and for dryness and light sensitivity at visit 6 (p ≤ 0.05).
Conclusions: LE/T satisfied all conditions of noninferi-ority to DM/T in comfort and tolerability. Subjects receiving LE/T were more likely to report better ocular comfort/tolerability ratings relative to baseline artificial tears than subjects receiving DM/T.
Limitations: The study population consisted of healthy volunteers.
To report the incidence and management of elevated intraocular pressure (IOP) in patients with uveitis treated with the fluocinolone acetonide (FA) intravitreal implant.
Pooled data from 3 ...multicenter, double-masked, randomized, controlled, phase 2b/3 clinical trials evaluating the safety and efficacy of the 0.59-mg or 2.1-mg FA intravitreal implant or standard therapy were analyzed.
During the 3-year follow-up, 71.0% of implanted eyes had an IOP increase of 10 mm Hg or more than baseline and 55.1%, 24.7%, and 6.2% of eyes reached an IOP of 30 mm Hg or more, 40 mm Hg or more, and 50 mm Hg or more, respectively. Topical IOP-lowering medication was administered in 74.8% of implanted eyes, and IOP-lowering surgeries, most of which were trabeculectomies (76.2%), were performed on 36.6% of implanted eyes. Intraocular pressure-lowering surgeries were considered a success (postoperative IOP of 6-21 mm Hg with or without additional IOP-lowering medication) in 85.1% of eyes at 1 year. The rate of hypotony (IOP </= 5 mm Hg) following IOP-lowering surgery (42.5%) was not different from that of implanted eyes not subjected to surgery (35.4%) (P = .09).
Elevated IOP is a significant complication with the FA intravitreal implant but may be controlled with medication and surgery.
Background Quantitative measures of alcohol intake are not always available in population studies. Methods The authors evaluated whether a question on alcohol intake embedded within a general health ...survey could be used as a surrogate marker for alcohol intake. We compared alcohol intake assessed with a food frequency questionnaire (FFQ) with alcohol intake assessed with a simple dichotomous survey question in a population-based sample. Results The study population consisted of 755 men and 1164 women from two communities in southeastern New England in the USA. There was strong agreement between the two alcohol questions for the classification of nondrinkers (98.1%). When participants were classified according to the quantity of alcohol consumed on the FFQ, the ability of the simple question to Identify drinkers Improved in a dose-response fashion. The Kappa statistic was 0.08 (P < 0.001), 0.38 (P < 0.001), and 0.81 (P < 0.001) for low, medium, and high consumers of alcohol, respectively. Conclusions These results suggest that the survey alcohol question provides a useful qualitative measure of categorizing nondrinkers and identifying drinkers who consume more than one drink per day. In population studies where quantitative measures of alcohol intake may not be available a survey alcohol question may prove useful when alcohol intake is likely to confound results, and adjustment of the data is needed.
To report 5-year postoperative safety data of iStent inject, including overall stability, endothelial cell density (ECD), and endothelial cell loss (ECL) in patients with mild-to-moderate primary ...open-angle glaucoma (POAG).
5-year follow-up safety study of the prospective, randomized, single-masked, concurrently controlled, multicenter iStent inject pivotal trial.
In this 5-year follow-up safety study of the 2-year iStent inject pivotal randomized controlled trial, patients receiving iStent inject placement and phacoemulsification or phacoemulsification alone were studied for the incidence of clinically relevant complications associated with iStent inject placement and stability. Corneal endothelial endpoints were mean change in ECD from screening and proportion of patients with >30% ECL from screening, from analysis of central specular endothelial images by a central image analysis reading center at several time points through 60 months postoperatively.
Of the 505 original randomized patients, 227 elected to participate (iStent inject and phacoemulsification group, n = 178; phacoemulsification-alone control group, n = 49). No specific device-related adverse events or complications were reported through month 60. No significant differences were observed in mean ECD, mean percentage change in ECD, or proportion of eyes with >30% ECL between the iStent inject and control groups at any time point; mean percentage decrease in ECD at 60 months was 14.3% ± 13.4% in the iStent inject group and 14.8% ± 10.3% in the control group (P = .8112). The annualized rate of ECD change from 3 to 60 months was neither clinically nor statistically significant between groups.
Implantation of iStent inject during phacoemulsification in patients with mild-to-moderate POAG did not produce any device-related complications or ECD safety concerns compared to phacoemulsification alone through 60 months.
Data from the Hemophilia Growth and Development Study (HGDS) were used to evaluate the association between hemophilia morbidity, measured by abnormalities in coordination and gait (CG), and ...intellectual ability and academic achievement. The CG abnormalities observed in the HGDS participants (n = 333) were primarily due to hemophilia-related morbidity. Although HGDS participants performed within the average range for age on measures of intellectual ability, there were meaningful differences between CG outcomes at baseline and throughout the 4 years of study. Participants without CG abnormalities consistently achieved higher scores than those with CG abnormalities on Reading, Spelling, and Arithmetic subtests of the Wide Range Achievement Test–Revised. Our findings suggest that lowered achievement is related to the functional severity of hemophilia. (J Pediatr 1998;133:782-7)
To assess the efficacy, safety, and tolerability of a topical water-free cyclosporine A formulation (CyclASol 0.1% ophthalmic solution) in comparison with vehicle for the treatment of dry eye disease ...(DED).
Three hundred twenty-eight patients were enrolled in this prospective, 12-week, multicenter, randomized, double-masked, confirmatory, vehicle-controlled clinical study. After a 2-week run-in period, eligible DED patients were randomized 1:1 to either CyclASol 0.1% or vehicle twice daily. The primary efficacy endpoint was change from baseline in total corneal fluorescein staining (National Eye Institute scale), and the second hierarchical primary efficacy endpoint was change from baseline in the Ocular Surface Disease Index score, both at 4 weeks. Secondary efficacy and safety assessments included conjunctival lissamine green staining (Oxford scale), visual analog scales for dry eye symptoms, and adverse event.
Treatment with CyclASol 0.1% was superior to vehicle in the primary endpoint: total corneal fluorescein staining at week 4 (Δ -0.8; 95% confidence interval, -1.3 to -0.4; P = 0.0002, analysis of covariance). This difference had already reached statistical significance after 2 weeks and was maintained throughout the study. The study did not statistically meet its second hierarchically tested primary endpoint: Ocular Surface Disease Index score (P = 0.2634). However, CyclASol 0.1% treatment showed statistically significant improvement compared with that of vehicle in the eye dryness score at week 4 (Δ -4.783; 95% confidence interval, -9.129 to -0.438; P = 0.0311).
CyclASol 0.1% was effective in treating signs and symptoms of DED. It significantly reduced corneal and conjunctival staining and improved ocular dryness compared with vehicle. CyclASol 0.1% was safe and showed excellent tolerability.
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