125/C0130
`
`Randomized, Placeb1:>-Controlled, Integrated Phase III Clinical Trials of a Once Daily, Low(cid:173)
`Concentration, MC>dified Bromfenac Ophthalmic Solution Following Cataract Surgery:
`Foc:us on Zero to Trace Anterior Chamber Inflammation
`
`J.AI. Gow1, J.D. Boyce2, H.J. Reiser3, R. Berry4, J.T. Dao5, and S.P. Chandler1
`for the Low Concentration Bromfenac Ophthalmic Solution Once Daily Study Group
`1Bausch & Lomb Inc., Irvine, CA, 20range County Ophthalmology Medical Group, Garden Grove, CA, 3 Eye Care Specialists, Kingston, PA, 4Eye Care Arkansas PA Little Rock, AR, 5Cornea Consultants of Arizona, Phoenix, AZ
`
`Phase 3, placebo-controlled, randomized, double-masked, multi(cid:173)
`center study
`
`440 subjects randomized (222 111 the bromfenac group, 218 111 the
`placebo group)at 39 clinical sites
`
`Eligible subjects were scheduled for a unilateral cataract surgery
`(phacoemulsification or extracapsular) with PCIOL implantation
`
`Screening Phase:: Days ~s to -1
`• Subjects were :11ssigned to receive either bromfena~:
`Pphthalmic sol1.1tipn or plo;u:;ebq. ®sed QD
`• Subjects must !have met inclusion and exclusion criteria to be
`~~~d--
`
`• Primary efficacy endpoint was clearance pf ocular
`inflammation [:Summed Ocular lnflammation Score (SOlS) ""
`01 by day 15
`• Secondary effic:acy endpoint was proportion of subjects with
`trace inflammation (SOlS= o-O.S)
`
`· ..
`
`;:
`:;
`:;
`I
`•• ~':,,l':,:
`
`{Treatment Phase: Day -1 to Day 15
`
`~;~~~::~~=:~~~~J :: ::: :::::: :: ::::~:,,:::::~:.~,::of
`
`l•Subjects began dosing on Day -1 (tv 24 hours before surgery)
`
`:;
`safety and efficac:y
`~l
`~~~:~~t~~~~~i~~~:~ to the office on Day 8±1 for evaluation of
`:;
`•Discontinued test agent on day 14 and subjects returned to the
`.;
`office on Day 15:1::1 for evaluation of safety and effica·cy
`•·••••••••••••••••••••••••••••••••••••••••••·••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••·••••••••••••••••••••••••••••••···•
`
`. \
`
`;~
`
`::
`
`Brumfenac is a non-steroidal anti inflammatory drug (NSAID) with an
`extensive history of cliniccd efficacy; it acts by blocking prostaglandin
`synthesis by inhibiting cyclooxygenase 1 and 2 in the arachidonic acid
`pathway 1
`
`The bromine moiety in bromfenac enhances lipophilicity and facilitates
`penetration throughout ocular tissues 2 - 3
`
`initially
`Brunuck® (brumfenac sodium ophthalmic solution) 0.1% was
`approved in Japan in July .2.000 and was subsequently approved for the
`treatment of blepharitis, conjunctivitis, scleritis (including episcleriti';) and
`post-operative inflammation4
`
`XibromTM (bromfenac ophthalmic solution) 0.09%, administered twice
`daily, was approved by the Food and Drug Administration (FDA) on March
`for the
`treatment of patients with post-cataract ocular
`24, 2005
`inflammation, and in January 2006 for the treatment of oculal- pain
`following cataract surgery4
`
`BromdayTM (bromfenac ophthalmic solution) 0.09% administered once
`daily, was approved by the FDA on October 16, 2010 for the treatment of
`postoperative inflammation and reduction of ocular pain in patients who
`have undergone cataract e:xtractionl
`
`Based on extensive post-marketing experience and data from clinical
`trials, bromfenac ophthalmic solution has demonstrated a favorable
`safety profile
`
`intraocular
`facilitates
`of bromfenac
`formulation
`The advanced
`penetration, thereby allowing a lower medication load while maintaining
`clinical efficacy with once daily dosing
`
`in a post-hoc analysis
`reduction of ocular
`the
`o~: To evaluate
`inflammation to 0 or trace anterior chamber inflammation of
`advanced
`formulation,
`low-concentration, bromfenac ophthalmic
`solution dosed once daily compared to placebo following cataract
`surgery in 2 integrated clinical trials.
`
`Presented at the SSth Annual Meeting of The Association for Research in Vision and Ophthalmology, Inc.; May 5-9, 2013; Seattle, WA.
`
`Anterior Chamber Cells
`
`Anterior Chamber Flare
`
`Percent Compliance
`
`Grade
`
`Cell Count
`
`Grade
`
`Flare Count
`
`1-5 cells (trace)
`
`6-15
`
`16-25
`
`26-50
`
`>50
`
`Complete absence
`
`Very slight (barely visible)
`
`Moderate (iris and lens clear)
`
`Marked (iris and lens hazy)
`
`Intense (fibrin clot)
`
`o Bromfenac 0.07% (n=222)
`
`_,.Placebo (n=218)
`
`71.2
`
`100
`
`c 90
`0
`
`:0 E 80 I 70
`
`Q)
`
`"' f:: 60
`g'
`~ 50
`~
`1'l 40
`:G
`~ 30
`iii 20
`t'
`& 10
`
`0
`
`8
`Day
`
`15
`
`Mean1
`
`Early Discontinuations
`
`Subjects who discontinued
`test agent early
`
`Due to lack of efficacy
`
`Bromfenac
`(n = 222)
`91.21%
`
`Placebo
`(n = 218)
`75.98%
`
`34 (15.3%)
`
`96 (44.0%)
`
`7 (3.2%)
`
`52 (23.9%)
`
`'%Ccmpl1mce
`
`100xnumberofdosesrece1ved/i6
`
`14(6.6%.)
`
`43 (21.1%)
`
`Eye Pain
`
`Anterior chamber inflammation
`
`Conjunctival hyperemia
`
`Photophobia
`
`Corneal edema
`
`Lacrimation increased
`
`Foreign body sensation
`
`6 (2.8%)
`5 (2.4%)
`
`2 (0.9%)
`1 (0.5%)
`1 (0.5%)
`
`1 (0.5%)
`0
`
`16 (7.8%)
`11 (5.4%)
`
`8 (3.9%)
`8 (3.9%)
`5 (2.5%)
`
`5 (2.5%)
`5 (2.5%)
`4
`
`o- The incidence of CME/ME was 0.5% (1/212) in the bromfenac
`group compared with 2.0% (4/204) in the placebo group.
`
`low-concentration
`formulation,
`Advanced
`bromfenac ophthalmic solution dosed once daily
`effedively
`and
`safely
`reduced
`ocular
`inflammation associated with cataract surgery.
`Once daily bromfenac ophthalmic solution
`0.07% was approved on April Sth, 2013 by the
`U.S. Food and Drug Administration (FDA) as
`PROLENSA lM 6
`
`PROL0280756
`
`SENJU EXHIBIT 2224
`INNOPHARMA v SENJU
`IPR2015-00903
`
`PAGE 1 OF 1
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