A Prospective, Randomized Trial of Povidone-Iodine 0.6% and Dexamethasone 0.1% Ophthalmic Suspension for Acute Bacterial Conjunctivitis.

PURPOSE: To evaluate the efficacy and safety of a topical ophthalmic suspension combination of povidone-iodine 0.6% (PVP-I) and dexamethasone 0.1% (DEX) for infectious and inflammatory components of bacterial conjunctivitis. DESIGN: Randomized, double-masked, multicenter, phase 3 clinical trial. METHODS: Subjects of all ages (those <3 months had to be full-term) with a diagnosis of bacterial conjunctivitis were randomized 3:1:3 to either PVP-I/DEX, PVP-I alone, or placebo. The primary endpoint was clinical resolution in the study eye, and the key secondary efficacy endpoint was bacterial eradication, both at the day 5 visit. Adverse events (AEs) were documented at all visits. RESULTS: Overall, 753 subjects were randomized (intent-to-treat [ITT] population; PVP-I/DEX [n = 324]; PVP-I [n = 108]; placebo [n = 321]); mean and standard deviation (SD) age was 44.3 (22.9) years, and most were female (61.2%) and white (78.1%). In all treatment groups, mean treatment compliance was >98%. The modified ITT population for the efficacy analysis comprised 526 subjects. In the study eye at the day 5 visit, clinical resolution was achieved by 50.5% (111/220) subjects in the PVP-I/DEX group vs 42.8% (95/222) in the placebo group (P = .127), and bacterial eradication was achieved by 43.3% (94/217) and 46.8% (102/218), respectively (P = .500). Treatment-emergent AEs were experienced by 32.8% (106/323), 39.8% (43/108), and 19.0% (61/321) of subjects in the safety population treated with PVP-I/DEX, PVP-I, and placebo, respectively (most mild in severity). CONCLUSION: In this study, PVP-I/DEX did not demonstrate additional benefit in clinical efficacy compared with placebo in subjects with bacterial conjunctivitis.

Kinetics of kill of bacterial conjunctivitis isolates with moxifloxacin, a fluoroquinolone, compared with the aminoglycosides tobramycin and gentamicin.

PURPOSE: To compare the kinetics and speed of kill of Streptococcus pneumoniae and Haemophilus influenzae on exposure to three topical ophthalmic antibiotic solutions. MATERIALS AND METHODS: Bacterial conjunctivitis isolates of S. pneumoniae and H. influenzae were exposed to 1:1000 dilutions of moxifloxacin 0.5%, tobramycin 0.3%, gentamicin 0.3%, and water (control). At 15, 30, 60, 120, and 180 minutes after exposure, aliquots were collected, cells were cultured, and viable cell counts were determined using standard microbiological methods. RESULTS: Moxifloxacin achieved 99.9% kill (3-log reduction) at approximately 2 hours for S. pneumoniae and at 15 minutes for H. influenzae. Tobramycin and gentamicin did not achieve 3-log reduction of S. pneumoniae during the 180-minute study period. An increase in bacterial growth was noted for these isolates. Gentamicin took more than 120 minutes to achieve the 3-log reduction of H. influenzae and tobramycin did not reach the 3-log reduction of this pathogen during the 180-minute study period. CONCLUSION: Moxifloxacin killed S. pneumoniae and H. influenzae in vitro faster than tobramycin and gentamicin, suggesting its potential clinical benefit as a first-line treatment for bacterial conjunctivitis to minimize patient symptoms and to limit the contagiousness of the disease.

Betaxolol hydrochloride ophthalmic suspension 0.25% and timolol gel-forming solution 0.25% and 0.5% in pediatric glaucoma: a randomized clinical trial.

PURPOSE: To describe the safety profile and clinical response on elevated intraocular pressure (IOP) of betaxolol hydrochloride ophthalmic suspension 0.25% (betaxolol) and timolol maleate ophthalmic gel-forming solution (TGFS) (0.25% and 0.5%), in subjects under 6 years of age. METHODS: Subjects were randomized to betaxolol 0.25% (twice daily) or TGFS (daily) (0.25% or 0.5%) in this double-masked study. IOPs were obtained at the same time of day (9 AM) at 2 baseline visits and weeks 2, 6, and 12. Mean change from baseline in IOP was the primary efficacy parameter. RESULTS: One hundred five subjects were randomized (34 to betaxolol, 35 to TGFS 0.25%, 36 to TGFS 0.5%). Betaxolol, TGFS 0.25%, and TGFS 0.5% produced statistically significant mean reductions in IOP; mean reductions after 12 weeks of treatment were 2.3, 2.9, and 3.7 mm Hg, respectively. In subjects who were not being treated with topical IOP-lowering medication at baseline, mean IOP reductions after 12 weeks of treatment were 3.1, 4.8, and 3.8 mm Hg, respectively. In patients discontinuing 1 or more topical IOP-lowering medications at baseline, mean IOP reductions at Week 12 were 1.8, 1.8, and 3.7 mm Hg, respectively. Responder rates (> or =15% reduction from baseline) for betaxolol, TGFS 0.25%, and TGFS 0.5% were 38.2, 45.7, and 47.2%, respectively. Adverse events were predominantly nonserious and did not interrupt patient continuation in the study. CONCLUSIONS: Betaxolol ophthalmic suspension 0.25%, TGFS 0.25%, and TGFS 0.5% were well tolerated. Despite low responder rates, all 3 treatments produced statistically significant mean reductions in IOP in pediatric glaucoma subjects.

Efficacy of brinzolamide and levobetaxolol in pediatric glaucomas: a randomized clinical trial.

PURPOSE: To describe the safety and clinical response on elevated intraocular pressure (IOP) of brinzolamide and levobetaxolol in pediatric patients under 6 years of age. METHODS: A double-masked, randomized design. Pediatric patients were randomized to brinzolamide suspension, 1%, or levobetaxolol suspension, 0.5%, both dosed twice daily. IOPs at 9 AM were taken at screening, baseline, and weeks 2, 6, and 12. A descriptive study with mean change from baseline IOP, the primary efficacy parameter. RESULTS: Seventy-eight evaluable patients (32 brinzolamide and 46 levobetaxolol). Patients on no prestudy IOP-lowering therapy randomized to brinzolamide had mean IOP change from baseline ranging from -4.1 mm Hg (week 2) to -5.0 mm Hg (week 6). When all brinzolamide patients are considered, there was little mean change from baseline IOP due to the large number of patients enrolled without a washout of prior IOP-lowering therapy. Levobetaxolol patients had mean change from baseline, ranging from -1.8 mm Hg (week 6) to -2.9 mm Hg (week 2). Levobetaxolol patients on no prestudy therapy had mean IOP change from baseline ranging from -2.9 mm Hg (week 12) to -4.0 mm Hg (week 2). Brinzolamide was more efficacious for glaucoma associated with systemic or ocular abnormalities and less efficacious for primary congenital glaucoma. Levobetaxolol was most efficacious for primary congenital glaucoma. Adverse events were predominantly nonserious and did not interrupt patient continuation in the study. CONCLUSIONS: Both brinzolamide and levobetaxolol were well tolerated. Both drugs provided clinically relevant IOP reductions for patients not on a previous medication, although efficacy is, in part, contingent upon diagnosis.

Efficacy of olopatadine ophthalmic solution 0.2% in reducing signs and symptoms of allergic conjunctivitis.

Olopatadine hydrochloride ophthalmic solution 0.2% (Pataday, Alcon) is a new formulation of olopatadine hydrochloride ophthalmic solution, the first topical ocular antiallergic agent indicated for once-daily dosing. The aim of this study was to evaluate the safety, efficacy, onset, and duration of action of olopatadine 0.2% in the treatment of allergic conjunctivitis. Using the conjunctival allergen challenge, this double-masked, randomized by eye, parallel-group study included four visits over a 5-week period. Subjects were screened for eligibility (visit 1) and their ocular allergic responses were confirmed at visit 2. The efficacy of olopatadine in reducing the signs and symptoms of allergic conjunctivitis was evaluated at onset of action (visit 4) and 16 hours (visit 3) after masked medication instillation. The primary efficacy parameter was ocular itching. Safety parameters were also evaluated. Ninety subjects were evaluated. Olopatadine 0.2% was significantly (p < 0.001) more effective than placebo in the treatment of ocular itching at all time points at both the onset of action and the 16-hour allergen challenges. Olopatadine 0.2% was significantly (p < 0.03) more effective than placebo in the reduction of conjunctival redness, chemosis, and eyelid swelling at all time points (with the exception of conjunctival redness, which was significantly reduced at five of six time points). There were no serious adverse events and no treatment-related adverse events. Once-daily dosing with olopatadine 0.2% reduced the signs and symptoms of allergic conjunctivitis with a rapid and prolonged duration of action. Safety analyses indicated that olopatadine 0.2% was safe and well tolerated in subjects with a history of allergic conjunctivitis.

Safety and tolerability of olopatadine 0.2% in children and adolescents.

OBJECTIVE: The aim of this study was to evaluate the safety of olopatadine hydrochloride ophthalmic solution 0.2% in children and adolescents 3-17 years of age. METHODS: In this 6-week, randomized, double-masked safety evaluation, eligible subjects with asymptomatic eyes underwent in-office visits at weeks 1, 3, and 6 and were contacted by telephone at weeks 2, 4, and 5. Qualified subjects were assigned randomly in a 2:1 ratio of olopatadine 0.2% to vehicle (identical formation without the active ingredient) for dosing on a once-daily schedule. Safety parameters assessed included adverse events, visual acuity, ocular signs (slit-lamp assessments), dilated fundus examinations, intraocular pressure (IOP), pulse, and blood pressure. RESULTS AND DISCUSSION: An evaluation of 126 subjects (age range, 3-17) revealed no clinically relevant treatment-related changes in visual acuity, IOP, slit-lamp assessments, fundus examinations, or cardiovascular parameters. All adverse events reported were mild or moderate. CONCLUSIONS: Olopatadine 0.2% administered once-daily for 6 weeks is safe and well tolerated in children and adolescent patients.

Perception and quality of life associated with the use of olopatadine 0.2% (Pataday) in patients with active allergic conjunctivitis.

This 28-d, open-label, multicenter, single-arm clinical study was designed to evaluate perceptions of olopatadine 0.2% in patients with active ocular allergic signs and symptoms. The study enrolled 330 patients, 5 to 94 y of age, who had previously used olopatadine 0.1% for active allergic conjunctivitis. Most patients were white (n=230; 70.1%) and female (n=239; 72.9%). Of all enrolled patients, 328 were evaluable for analysis. Throughout the study, patients instilled 1 drop of olopatadine 0.2% into each eye once daily; adverse events were documented and ocular evaluations were conducted to ensure patient safety. Direct evaluations of efficacy were not performed. On days 1 and 7, patients completed the Rhinoconjunctivitis Quality of Life Questionnaire, recorded their perceptions of olopatadine 0.1% (day 1) or 0.2% (day 7), and had their ocular allergies assessed globally. On each of the first 6 d of treatment, patients also completed a telephone-based perception questionnaire. On day 28, patients returned to the study center, reported their treatment perceptions, had their ocular allergies assessed, and exited the trial. Overall, patients had a positive perception of olopatadine 0.2%. Patients were more satisfied with olopatadine 0.2% than they remembered being with olopatadine 0.1% (289 vs 257 patients; 87.6% vs 77.8%; P<.05). The majority of the 48 patients who wore contact lenses (n=42; 88%) believed that they could wear their contacts as desired. Significant improvement was noted in all categories of the Rhinoconjunctivitis Quality of Life Questionnaire (P<.0001). No unexpected safety findings were reported. Patients perceived olopatadine 0.2% to be effective and well tolerated.

Randomized, placebo-controlled evaluation of Cerumenex and Murine earwax removal products.

OBJECTIVE: To evaluate the efficacy of 2 ceruminolytic products, Cerumenex Eardrops (Purdue Frederick Company, Norwalk, Conn) and Murine Ear Drops (Abbott Laboratories, Abbott Park, Ill), in subjects with partial or complete occlusion of the ear canal due to cerumen. DESIGN: Randomized, subject- and observer-blind, placebo-controlled, clinical trial. SETTING: Corporate research clinic. PARTICIPANTS: From among 230 volunteers screened, 74 subjects (age, 22-66 [mean, 45] years) were enrolled in the study. Participants had baseline occlusion levels of mild (n = 10), moderate (n = 26), or complete (n = 38) impairment of tympanic membrane visualization. INTERVENTIONS: Subjects were randomly assigned to 1 of 3 treatments: Cerumenex (10% triethanolamine polypeptide oleate-condensate), Murine (6.5% carbamide peroxide), and a placebo, BSS Sterile Irrigating Solution (Alcon Laboratories Inc, Ft Worth, Tex). The test medication was instilled into 1 occluded ear for up to two 15-minute applications. Following the treatment, the subject's ear was irrigated with 50 mL of lukewarm water delivered at low pressure via a WaterPik irrigator equipped with a Grossan irrigator tip. Main Outcome Measure The degree of occlusion, measured against a previously established 4-point scale, was assessed and recorded at baseline and after each instillation and irrigation procedure. RESULTS: Neither Cerumenex nor Murine was superior to saline placebo. By the end of treatment, 29.2%, 15.4%, and 41.7% of subjects treated with Cerumenex, Murine, and placebo, respectively, experienced resolution of cerumen occlusion. These values were not statistically significantly different from one another. CONCLUSION: The currently marketed ceruminolytic products, Cerumenex and Murine, are no more effective than a saline placebo in removing earwax.

Clinical efficacy of olopatadine hydrochloride ophthalmic solution 0.2% compared with placebo in patients with allergic conjunctivitis or rhinoconjunctivitis: a randomized, double-masked environmental study.

BACKGROUND: Previous studies have suggested that olopatadine hydrochloride ophthalmic solution 0.2% administered once daily is effective for up to 24 hours after instillation and is well tolerated in adults and children aged > or =3 years. OBJECTIVE: The goal of this study was to evaluate the efficacy and safety profile of olopatadine 0.2% compared with placebo in patients with seasonal allergic conjunctivitis or rhinoconjunctivitis. METHODS: This was a 10-week, randomized, placebo-controlled, double-masked environmental study conducted during the spring allergy season (April-August) of 2003. Patients assessed their ocular signs and symptoms in terms of frequency (whole-unit scale from 0 to 5) and severity (half-unit scale from 0 to 4), and grass pollen counts were obtained daily for each investigative site. Responder analyses were conducted by pollen level (frequency based) and pollen period (severity based) to evaluate the clinical significance of differences in ocular itching and redness between treatment groups. RESULTS: Two hundred sixty patients (137 females, 123 males) were enrolled in the study, including 28 children aged between 11 and 17 years; the overall population was 74% white, 11% black, 4% Hispanic, and 11% other. The frequency-based responder analyses of ocular itching and redness showed that when grass pollen counts were high (>20 gr/m(3) air), a respective 21% and 14% of patients in the olopatadine 0.2% group assessed the frequency of ocular itching and redness as >2, compared with 47% and 31% of patients in the placebo group (P < 0.001 for ocular itching; P < 0.003 for redness). The results of the severity-based responder analyses by peak pollen period were consistent with those of the frequency-based analyses. Compared with placebo, olopatadine 0.2% was associated with significant reductions in calculated mean scores for ocular itching and redness by pollen level and by pollen period. No patient was discontinued from the study because of a treatment-related adverse event, and no patient experienced a treatment-related serious adverse event. CONCLUSION: In the patients studied, olopatadine 0.2% appeared to be effective and well tolerated when administered once daily for the treatment of the ocular signs and symptoms of allergic conjunctivitis or rhinoconjunctivitis.

Preclinical and clinical antiallergic effect of olopatadine 0.2% solution 24 hours after topical ocular administration.

Pharmacologic studies examined the potential of a solution containing olopatadine to maintain and extend antiallergic efficacy after single topical ocular drop administration over 24 hours. Results of these preclinical experiments conducted in guinea pigs indicated that olopatadine 0.2% (wt/vol) solution was significantly effective 24 hours after dosing. This concentration of olopatadine provided significantly more efficacy than Patanol (olopatadine 0.1%) 24 hours after administration while being as effective as Patanol (olopatadine 0.1%) 5 minutes after administration. Results from a human conjunctival allergen challenge trial in sensitive subjects confirmed clinical efficacy of olopatadine 0.2% solution over 24 hours. When individuals were challenged with antigen at onset, 16 and 24 hours after drug administration onto the eye, significant reductions were observed in the scores for active drug as compared with placebo for pruritus (77, 77, and 61%), conjunctival redness (35, 28, and 20%), and chemosis (53, 41, and 31%), respectively. These data suggest that topically applied olopatadine 0.2% solution will be an effective once-a-day therapy for allergic conjunctivitis.

Double-masked, randomized, parallel-group study comparing olopatadine 0.1% ophthalmic solution with cromolyn sodium 2% and levocabastine 0.05% ophthalmic preparations in children with seasonal allergic conjunctivitis.

BACKGROUND: It is estimated that >50% of medications have not been tested in children. Physicians need pediatric data to guide them in treating children. Olopatadine hydrochloride ophthalmic solution 0.1% is a topical antiallergic agent that is both an antihistamine with high affinity and selectivity for the histamine H1 receptor and a mast cell stabilizer that inhibits the release of histamine and other proinflammatory mediators from human conjunctival mast cells. The efficacy and tolerability of olopatadine has been demonstrated by comparative studies in adults and children with seasonal allergic conjunctivitis (SAC). OBJECTIVE: Pediatric patient data were extracted from 2 clinical trials to assess the efficacy and tolerability of olopatadine hydrochloride ophthalmic solution 0.1% compared with those of cromolyn sodium ophthalmic solution 2% and levocabastine ophthalmic solution 0.05% as treatment for SAC in children. METHODS: In study 1, conducted at 15 centers in 7 countries (Europe and Australia) from October 1995 to December 1997, olopatadine was instilled BID and placebo (vehicle) BID for 6 weeks and compared with cromolyn instilled QID. Study 2, conducted at 17 centers in 8 countries (Europe and Australia) from November 1998 to June 2000, compared olopatadine BID with levocabastine BID. In both studies, children of either sex and any race, aged 4 to 11 years, and having proven grass pollen allergies were assigned to treatment in a double-masked, randomized fashion. Slit-lamp examination, the physician's impression scale, and self-ratings were used to obtain efficacy data. Data analyses were based on pollen concentrations. The tolerability assessments were based on visual acuity, pupil diameter, intraocular pressure, and a dilated fundus examination. RESULTS: Study 1 comprised 30 children (olopatadine [n = 13] and cromolyn sodium [n = 17]; 18 boys, 12 girls; mean age, 7.9 years [range, 4-11 years]). Study 2 comprised 22 children (olopatadine [n = 10] and levocabastine [n = 12]; 12 boys, 10 girls; mean age, 8.6 years [range, 5-11 years]). In study 1, ocular itching (P = 0.010), redness seen on slit-lamp examination (P = 0.003), and eyelid swelling (P = 0.034) were significantly less intense with olopatadine than with cromolyn sodium during the peak pollen period. In study 2, redness seen on slit-lamp examination (P = 0.040) and self-rated ocular redness (P = 0.024) were significantly less intense with olopatadine than levocabastine during the peak pollen period. Olopatadine was well tolerated. CONCLUSION: Olopatadine hydrochloride ophthalmic solution 0.1% was more effective than both cromolyn sodium 2% and levocabastine 0.05% ophthalmic preparations in controlling ocular signs and symptoms of SAC in children and was well tolerated when administered twice daily for 6 weeks.