title: Six-Month Intraocular Pressure Reduction with a Topical Bimatoprost Ocular Insert: Results of a Phase II Randomized Controlled Study.
abstract: Improving adherence to manage elevated intraocular pressure (IOP) remains an unmet need. A topical bimatoprost ocular insert was compared with twice-daily timolol eye drops in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) treated for 6 months.
  
  
  
  Parallel-arm, multicenter, double-masked, randomized, controlled trial.
  
  
  
  One hundred thirty adult OAG or OHT patients.
  
  
  
  Eligible patients were randomized 1:1 to receive a bimatoprost insert plus artificial tears twice daily or a placebo insert plus timolol (0.5% solution) twice daily for 6 months after a screening washout period. Diurnal IOP measurements (at 0, 2, and 8 hours) were obtained at baseline; weeks 2, 6, and 12; and months 4, 5, and 6. Key eligibility included washout IOP of 23 mmHg or more at time 0, IOP of 20 mmHg or more at 2 and 8 hours, and IOP of 34 mmHg or less at all time points; no prior incisional surgery for OAG or OHT; and no known nonresponders to prostaglandins.
  
  
  
  The primary efficacy end point examined the difference in mean change from baseline in diurnal IOPs (point estimate, 95% confidence interval) across 9 coprimary end points at weeks 2, 6, and 12 comparing the bimatoprost arm with the timolol arm using a noninferiority margin of 1.5 mmHg. Secondary end points were diurnal IOP measurements at months 4, 5, and 6 and adverse events (AEs).
  
  
  
  A mean reduction from baseline IOP of -3.2 to -6.4 mmHg was observed for the bimatoprost group compared with -4.2 to -6.4 mmHg for the timolol group over 6 months. The study met the noninferiority definition at 2 of 9 time points but was underpowered for the observed treatment effect. Adverse events were consistent with bimatoprost or timolol exposure; no unexpected ocular AEs were observed. Primary retention rate of the insert was 88.5% of patients at 6 months.
  
  
  
  Clinically relevant reduction in mean IOP was observed over 6 months with a bimatoprost ocular insert and seems to be safe and well tolerated. The topically applied bimatoprost insert may provide an alternative to daily eye drops to improve adherence, consistency of delivery, and reduction of elevated IOP.
authors.affiliation: Department of Ophthalmology & Vision Science, University of California, Davis, Sacramento, California. Electronic address: jdbrandt@ucdavis.edu.
authors.forename: James D
authors.initials: JD
authors.lastname: Brandt
authors.affiliation: Sall Research Medical Center, Artesia, California.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Sall
authors.affiliation: Clayton Eye Center, Morrow, Georgia.
authors.forename: Harvey
authors.initials: H
authors.lastname: DuBiner
authors.affiliation: Apex Eye, Cincinnati, Ohio.
authors.forename: Robert
authors.initials: R
authors.lastname: Benza
authors.affiliation: ForSight VISION5, Inc., Menlo Park, California.
authors.forename: Yair
authors.initials: Y
authors.lastname: Alster
authors.affiliation: ForSight VISION5, Inc., Menlo Park, California.
authors.forename: Gary
authors.initials: G
authors.lastname: Walker
authors.affiliation: ForSight VISION5, Inc., Menlo Park, California.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Semba
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069580:Bimatoprost / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013999:Timolol / Q000009:adverse effects / Q000627:therapeutic use; D014065:Tonometry, Ocular
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D013999:Timolol; D000069580:Bimatoprost