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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.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.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.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.ClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364.

BackgroundThe 0.2 µg/day fluocinolone acetonide (FAc) implant delivers continuous, low-dose, intravitreal corticosteroid for the treatment of diabetic macular oedema (DMO). This ongoing, 3-year, observational clinical trial provides long-term, ‘real-world’ safety results for the FAc implant in DMO.MethodsThis 24-month interim analysis of a prospective, observational study investigated patients with DMO receiving the commercially available intravitreal 0.2 µg/day FAc implant. The primary outcome was incidence of intraocular pressure (IOP)-lowering procedures. Other IOP-related signals and their relationship to previous corticosteroid exposure, best-corrected visual acuity, central subfield thickness (CST), ocular adverse events and frequency of other treatments were also measured.ResultsData were collected from 95 previously steroid-challenged patients (115 study eyes) for up to 36 months pre-FAc and 24 months post-FAc implant. Mean IOP for the overall population remained stable post-FAc compared with pre-FAc implant. IOP-related procedures remained infrequent (two IOP-lowering surgeries pre-FAc; two trabeculoplasties and four IOP-lowering surgeries post-FAc). Mean visual acuity was stable post-FAc (mean improvement of 1–3 letters) and fewer DMO treatments were required per year following FAc implant. Mean CST was significantly reduced at 24 months post-FAc implant (pConclusionFew IOP-related procedures were reported during the 24 months post-FAc implant. Positive efficacy outcomes were noted after treatment, with stabilisation of vision and reduction in inflammation, demonstrated by CST. The FAc implant has a favourable benefit–risk profile in the management of DMO, especially when administered after a prior steroid challenge.Trial registration numberNCT02424019.

Background: Venlafaxine extended-release (ER) tablets use osmotic pressure to deliver venlafaxine hydrochloride at a controlled rate over ~24 hours. Objective: These studies were conducted to evaluate the bioequivalence of venlafaxine ER tablets and capsules based on the US Food and Drug Administration (FDA) definition. Methods: Four pharmacokinetic studies of the capsule (reference) and tablet (test) formulations were conducted in healthy adult volunteers. The first 2 were randomized, single-dose, 4-way crossover studies of either a 37.5-mg dose (study A) or a 75-mg dose (study B) of the reference and test products under fasting and fed conditions. The other 2 were randomized, 2-way crossover studies of either a single dose (study C) or multiple doses (study D) of venlafaxine ER 225 mg, delivered as one venlafaxine ER 225-mg tablet or one 150-mg + one 75-mg venlafaxine ER capsules under fed conditions. The primary outcome measures were the log-transformed C max , AUC 0−t , and AUC 0−∞ . If the 90% CIs for the ratios of the least squares means of the primary outcome measures between the reference and test formulations fell within the regulatory range (80%–125%), the 2 formulations would be considered bioequivalent according to the FDA definition. Results: Thirty–six subjects (21 men, 15 women; mean [SD] age, 28.0 [8.7] years; mean weight, 161.0 [26.0] lb) were enrolled in study A and completed all treatment periods. Thirty-six subjects were enrolled in study B, of whom 30 (22 men, 8 women; mean age, 33.5 [9.6] years; mean weight, 172.7 [23.9] lb) completed all treatment periods. Thirty-six subjects were enrolled in study C, of whom 28 (16 men, 12 women; mean age, 33.1 [12.9] years; mean weight, 160.6 [29.6] lb) completed the study. Thirty-four subjects were enrolled in study D, of whom 33 (29 men, 4 women; mean age, 26.0 [8.1] years; mean weight, 178.0 [30.3] lb) completed the study. In study A, the 90% CIs for the log-transformed ratio (test vs reference) of C max , AUC 0−t , and AUC 0−∞ in the fasted state were 95.58 to 107.48, 97.58 to 111.09, and 100.31 to 112.85, respectively; in the fed state, the corresponding values were 84.26 to 94.86, 93.49 to 106.58, and 98.98 to 111.91. In study B, the respective values in the fasted state were 113.07 to 126.10, 111.11 to 124.57, and 106.86 and 120.71; in the fed state, the values were 90.50 to 100.90, 96.80 to 108.50, and 95.05 to 107.21. In study C, fed values were 94.15 to 109.37, 103.8 to 115.85, and 102.64 to 113.39. In study D, which involved multiple doses, fed values for C max and AUC 0−t were 82.26 to 88.77 and 101.16 to 109.45, respectively. Adverse effects included nausea, vomiting, dizziness, syncope, and somnolence. Conclusions: In these single- and multiple-dose studies, all doses of venlafaxine ER tablets tested met the FDA criterion for bioequivalence to the equivalent doses of venlafaxine ER capsules in the fed state. In the fasted state, the bioequivalence criterion was met for venlafaxine ER 37.5-mg tablets but not venlafaxine 75-mg tablets.