Single Administration of Intracameral Bimatoprost Implant 10 µg in Patients with Open-Angle Glaucoma or Ocular Hypertension.

INTRODUCTION: This study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension. METHODS: Two identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 study datasets evaluated outcomes in the 10-µg bimatoprost implant and comparator treatment arms after a single implant administration, up to the time of implant re-administration or rescue with IOP-lowering medication. RESULTS: In the phase 3 studies, 10-µg bimatoprost implant single administration demonstrated IOP reductions (hour 0) of 4.9-7.0 mmHg through week 15 from a mean (standard deviation, SD) baseline IOP of 24.5 (2.6) mmHg (n = 374); IOP in the topical timolol BID group was reduced by 6.0-6.3 mmHg from a mean (SD) baseline IOP of 24.5 (2.6) mmHg (n = 373). In the phase 1/2 study (n = 21), median time to use of additional IOP-lowering treatment (Kaplan-Meier analysis) was 273 days (approximately 9 months), and 5 of 21 enrolled patients (23.8%) required no additional IOP-lowering treatment up to 24 months after single administration. In each study, after a single implant administration there were no reports of corneal edema, corneal endothelial cell loss, or corneal touch, and no patients had 20% or greater loss in corneal endothelial cell density. CONCLUSIONS: Bimatoprost implant single administration lowers IOP and has a favorable safety profile. Additional studies are needed to further evaluate the duration of effect and factors predicting long-term IOP lowering after a single implant administration. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364.

Three-year effectiveness and safety of the XEN gel stent as a solo procedure or in combination with phacoemulsification in open-angle glaucoma: a multicentre study.

PURPOSE: To assess the 3-year effectiveness and safety of the XEN gel stent implanted ab interno in open-angle glaucoma (OAG). METHODS: This study was a multicentre, retrospective chart review of consecutive patients with OAG who underwent ab-interno gel stent placement alone or combined with phacoemulsification between 1 January 2014 and 1 October 2015. Outcome measures included mean changes in intraocular pressure (IOP) and IOP-lowering medication count from medicated baseline at 1, 2, 3 (primary outcome) and 4 years (if available) postimplantation. Intraoperative complications, adverse events of special interest (AESIs) and secondary surgical interventions (SSIs) were recorded. RESULTS: The safety and effectiveness populations included 212 eyes (primary and secondary) and 174 eyes (primary), respectively. Mean IOP and medication decreased from 20.7 mmHg and 2.5 at baseline (n = 163 primary/first implanted eyes) to 13.9 mmHg and 1.1 medications (n = 76) at 3 years postimplantation, respectively. Mean changes from baseline in IOP (-5.6, -6.2 and -6.6 mmHg) and IOP-lowering medication count (-1.8, -1.6 and -1.4) were statistically significant at 1, 2 and 3 years postimplantation, respectively. Results appeared comparable when implantation was performed with (n = 76) or without (n = 98) phacoemulsification. In primary eyes with 4-year IOP and medication count data (n = 27), mean IOP was 14.0 mmHg on 1.3 medications at 4 years postimplantation. Fifteen (7.1%) eyes had intraoperative complications, 31 (14.6%) experienced 46 postoperative AESIs, and 26 (12.3%) required SSI. CONCLUSION: The gel stent effectively lowered IOP and IOP-lowering medication count over 3 years, with a predictable and acceptable safety profile, when implanted via the traditional ab-interno technique.

Early and Consistent Improvements in Urinary Symptoms and Quality of Life With OnabotulinumtoxinA in Patients With Overactive Bladder and Urinary Incontinence: Results From a Randomized, Placebo-controlled, Phase IV Clinical Trial.

OBJECTIVES: This randomized, multicenter, placebo-controlled, phase IV study assessed the efficacy and tolerability of onabotulinumtoxinA in patients with overactive bladder. METHODS: Patients were randomized 1:1 to onabotulinumtoxinA 100 U or placebo. Assessments over 12 weeks included: change from baseline in urinary incontinence (UI) episodes/day; proportions of patients who achieved 100% and 50% or greater reductions in UI episodes/day; proportion of patients using no incontinence pads in the previous 24 hours; and changes from baseline in micturition frequency, nocturia, urgency UI, Incontinence-Quality of Life, King's Health Questionnaire, International Consultation on Incontinence Questionnaire-UI Short Form scores and time to request retreatment. RESULTS: Significant reductions in UI episodes/day were seen with onabotulinumtoxinA versus placebo within week 1 posttreatment (-2.9 vs -2.0, P = 0.005) through week 12 (coprimary endpoint: -3.5 vs -1.6, P < 0.001). Significantly more onabotulinumtoxinA-treated patients achieved 100% (coprimary endpoint) and 50% or greater reductions in UI episodes/day. Decreases in other urinary symptoms were also seen within 1 week with onabotulinumtoxinA that continued through at least week 12. More onabotulinumtoxinA-treated versus placebo-treated patients required no incontinence pads at weeks 1 to 12, and greater improvements in quality of life measurements were seen. Time to request retreatment was significantly longer with onabotulinumtoxinA versus placebo (30.0 weeks vs 13.1 weeks; P < 0.001). No unexpected safety signals were observed. Urinary tract infection was the most commonly observed adverse event. CONCLUSIONS: Urinary symptom and quality of life improvements were observed with onabotulinumtoxinA within 1 week of treatment and were sustained for at least 12 weeks.

Natural history of diabetic macular edema and factors predicting outcomes in sham-treated patients (MEAD study).

PURPOSE: To describe the natural history of diabetic macular edema (DME) with respect to best-corrected visual acuity (BCVA) and central retinal thickness (CRT) outcomes and to identify baseline patient characteristics and systemic factors associated with improvement or worsening of outcomes in sham-treated patients. METHODS: The study population was sham-treated patients (n = 350) in the 3-year MEAD registration study of dexamethasone intravitreal implant for treatment of DME. Patients had center-involved DME and received sham intravitreal injections in the study eye at ≥ 6-month intervals. Potential prognostic factors for outcomes were evaluated using multiple linear regression analysis. RESULTS: Visual and anatomic outcomes were poorer in patients who left the study early (n = 198) than in study completers (n = 152). Mean change in BCVA from baseline at the last visit with available data was + 0.9 letters; 37.5% of patients had no change in BCVA, 23.2% had gained > 10 letters, and 16.0% had lost > 10 letters. Older age and baseline diabetic retinopathy score > 6 were associated with worse BCVA outcomes; thicker baseline CRT and larger number of hypertension medications used were associated with larger reductions in CRT during the study. CONCLUSIONS: BCVA and CRT outcomes were variable in this population of DME patients with generally good glycemic control. In DME patients without active treatment, older age and baseline diabetic retinopathy score > 6 were associated with less improvement in BCVA; thicker baseline CRT and a larger number of antihypertensive medications used predicted better improvement in CRT. TRIAL REGISTRATION: The MEAD study trials are registered at ClinicalTrials.gov with the identifiers NCT00168337 and NCT00168389.

Once-Daily Topical Dapsone Gel, 7.5%: Effective for Acne Vulgaris Regardless of Baseline Lesion Count, With Superior Efficacy in Females

Introduction: Acne vulgaris is more common in females than males and is challenging to treat. A post hoc analysis of 2 clinical trials evaluated the effect of dapsone gel, 7.5% based on sex and baseline acne lesion count. Methods: Two identically designed, randomized, double-blind, vehicle-controlled, multicenter, 12-week, phase 3 trials enrolled patients aged ≥12 years with facial acne and 20 to 50 inflammatory and 30 to 100 comedonal lesions. Patients applied dapsone gel, 7.5% or vehicle topically once daily for 12 weeks. Baseline to week 12 reductions were evaluated for total, inflammatory, and comedonal lesions in the pooled dapsone population by sex and total baseline acne lesion count (low: 50­74, medium: 75­99, and high: ≥100). Results: The analysis included 2160 patients (56% female, 44% male). Males and females had similar average baseline total, inflammatory, and comedonal lesion counts. Low, medium, and high subgroups experienced efficacy with dapsone gel, 7.5%. Females in each subgroup experienced superior efficacy to males. In females, total lesion counts in the low, medium, and high subgroups decreased by 56.07%, 50.22%, and 47.63%, respectively, compared with 47.95%, 42.30%, and 34.68% in males (P<0.001 for each male-female comparison). Females' respective inflammatory lesion count percentage reductions were 60.96%, 57.91%, and 55.83%, versus 52.75% (P<0.001), 46.85% (P<0.001), and 44.70% (P=0.008) in males. Females' respective comedonal lesion count percentage reductions were 52.96%, 45.40%, and 44.22%, versus 44.67% (P<0.001), 39.38% (P=0.030), and 29.89% (P=0.001) in males. The TEAE rate was low for the overall population (18.3%) and similar for females (19.0%) and males (17.4%). Males and females had similarly favorable dermal tolerability. Conclusion: Once-daily dapsone gel, 7.5% was efficacious for acne regardless of baseline total lesion count, with superior efficacy in females and similar tolerability in males and females. Registration identifier: Clinicaltrials.gov: NCT01974141 and NCT01974323

Once-Daily Topical Dapsone Gel, 7.5%: Effective for Acne Vulgaris Regardless of Baseline Lesion Count, With Superior Efficacy in Females

Introduction: Acne vulgaris is more common in females than males and is challenging to treat. A post hoc analysis of 2 clinical trials evaluated the effect of dapsone gel, 7.5% based on sex and baseline acne lesion count. Methods: Two identically designed, randomized, double-blind, vehicle-controlled, multicenter, 12-week, phase 3 trials enrolled patients aged ≥12 years with facial acne and 20 to 50 inflammatory and 30 to 100 comedonal lesions. Patients applied dapsone gel, 7.5% or vehicle topically once daily for 12 weeks. Baseline to week 12 reductions were evaluated for total, inflammatory, and comedonal lesions in the pooled dapsone population by sex and total baseline acne lesion count (low: 50­74, medium: 75­99, and high: ≥100). Results: The analysis included 2160 patients (56% female, 44% male). Males and females had similar average baseline total, inflammatory, and comedonal lesion counts. Low, medium, and high subgroups experienced efficacy with dapsone gel, 7.5%. Females in each subgroup experienced superior efficacy to males. In females, total lesion counts in the low, medium, and high subgroups decreased by 56.07%, 50.22%, and 47.63%, respectively, compared with 47.95%, 42.30%, and 34.68% in males (P<0.001 for each male-female comparison). Females' respective inflammatory lesion count percentage reductions were 60.96%, 57.91%, and 55.83%, versus 52.75% (P<0.001), 46.85% (P<0.001), and 44.70% (P=0.008) in males. Females' respective comedonal lesion count percentage reductions were 52.96%, 45.40%, and 44.22%, versus 44.67% (P<0.001), 39.38% (P=0.030), and 29.89% (P=0.001) in males. The TEAE rate was low for the overall population (18.3%) and similar for females (19.0%) and males (17.4%). Males and females had similarly favorable dermal tolerability. Conclusion: Once-daily dapsone gel, 7.5% was efficacious for acne regardless of baseline total lesion count, with superior efficacy in females and similar tolerability in males and females. Registration identifier: Clinicaltrials.gov: NCT01974141 and NCT01974323

Once-Daily Topical Dapsone Gel, 7.5%: Effective for Acne Vulgaris Regardless of Baseline Lesion Count, With Superior Efficacy in Females

Introduction: Acne vulgaris is more common in females than males and is challenging to treat. A post hoc analysis of 2 clinical trials evaluated the effect of dapsone gel, 7.5% based on sex and baseline acne lesion count. Methods: Two identically designed, randomized, double-blind, vehicle-controlled, multicenter, 12-week, phase 3 trials enrolled patients aged ≥12 years with facial acne and 20 to 50 inflammatory and 30 to 100 comedonal lesions. Patients applied dapsone gel, 7.5% or vehicle topically once daily for 12 weeks. Baseline to week 12 reductions were evaluated for total, inflammatory, and comedonal lesions in the pooled dapsone population by sex and total baseline acne lesion count (low: 50­74, medium: 75­99, and high: ≥100). Results: The analysis included 2160 patients (56% female, 44% male). Males and females had similar average baseline total, inflammatory, and comedonal lesion counts. Low, medium, and high subgroups experienced efficacy with dapsone gel, 7.5%. Females in each subgroup experienced superior efficacy to males. In females, total lesion counts in the low, medium, and high subgroups decreased by 56.07%, 50.22%, and 47.63%, respectively, compared with 47.95%, 42.30%, and 34.68% in males (P<0.001 for each male-female comparison). Females' respective inflammatory lesion count percentage reductions were 60.96%, 57.91%, and 55.83%, versus 52.75% (P<0.001), 46.85% (P<0.001), and 44.70% (P=0.008) in males. Females' respective comedonal lesion count percentage reductions were 52.96%, 45.40%, and 44.22%, versus 44.67% (P<0.001), 39.38% (P=0.030), and 29.89% (P=0.001) in males. The TEAE rate was low for the overall population (18.3%) and similar for females (19.0%) and males (17.4%). Males and females had similarly favorable dermal tolerability. Conclusion: Once-daily dapsone gel, 7.5% was efficacious for acne regardless of baseline total lesion count, with superior efficacy in females and similar tolerability in males and females. Registration identifier: Clinicaltrials.gov: NCT01974141 and NCT01974323