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`Integrated Phase III Clinical Trials of Low-Concentration, Modified
`Bromfenac Ophthalmic Solution Dosed Once Daily for Cataract Surgery
`
`J.A. Gow,‘ D.F. Goldberg,’ J.H. Peace,’ T.R. Walters,‘ J.P. Gira,5 S.M. KIier,1 T.R. McNamara’
`for the Low Concentration Bromfenac Ophthalmic Solution Once Daily Study Group
`'Bausch & Lomh lnc., Irvine, CA; 53Wo|sta1 Eye Associats, Torrance, CA; ‘United Medical Rsearch lnstituha, Inglewood, CA; "Texan Eye, Austin, TX; ‘Ophthalmology Consultants, Ltd, St. Louis, MO
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`34 (15.3%)
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`5 (44,005)
`5z.(23.9%)
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`a (2.0%)
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`Subjects reporting an AE affecting
`the study eye or both eyes
`Eye Pain
`Amzrior diatribe’ inflammation
`Canjunctival hvperemia
`Phofluphobie
`Corneal edema
`Lacriination increased
`Forelgn body sensation
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`H (56%)
`6 (18%)
`5 (14%)
`2 (0 9%)
`I (0.9%)
`l (0.5%)
`1 (0.9%)
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`‘3 (2140).)
`16 (7.893)
`n (5.4%;
`8 (3.9%)
`E (3.9%)
`5(2.9'/5)
`S (1.5%)
`5 (2.5%)
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`lane-eoeeenlretioii, n;illlei! ‘HO-IGIIIC eolutlon 10:0 Qn
`ie eale aed efleeflve to treat he liillaeiiiietioe and pale
`aaeoclaaed wllli cataract surgery.
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`rnodllied brornlenac solubon doeed QD lar cataract surgery. :-ad ‘.=.i.it:,‘:-.::t5«
`low~cimi:enuation,
`elficacy and
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`. Sulijecb received either bramlenac (n-722) or placebo
`0 mgr :Eu:;acw°-(mun hd mmamceo oomlemus ed mun
`(n-218) Q0. Dosing began 1 day belore cataract surgery and
`continued dally through post-surgery Day 14. Prriiary efllcaey
`0 440 subjects randomized (222 in the bmmfenac group. 218 in the
`endpoint was no ocular inflammation by Day 15; secondary efllcacy
`placebo droun)al 39<|Iruca| sites
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`° Elgble subjects were scheduled for a unilateial cataract surgery
`to placebo for primary and
`firm
`Brornfanac was
`superior
`(phneoemulsll-cation or eaitraceosularj with FCIOL irnplantatlon
`eeeundary efficacy eridpoiritf (no 0001). Compared he plaralm,
`broinlenac had a biver
`incidence of ocular adverse evens
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`Ql) is safe and efioctiva tn Ina: the inflammatnn and pain associated
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`la-«navy:
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`6 Bromfenac IS a non-steroidal anti itiflamniabrv drw INSAID) with
`an eziteisive liismrv of clinical efficacy;
`it acts liv blockmg
`pmstaglanclin synthesis by inhibiting cyclonxygmase 1 and 2 in
`the aracmdonic acid pathway ‘
`A The bromine moiety in bmmrenac enhances Ilpaphiliclty and
`laclitaus penetration throughout ocular tissues 1'3‘
`A Bronucklié (hromfenac sodium ophthalmic solution) 0.1% was
`nmallv approved In Japan in July 2000 and was subsequently
`approved far the treatment of hlephantis. cunjiinctivitis. sclerib‘:
`(including epvscleritsl and poshooeiative inflamrnaoacv
`1 Xihrom"’
`(hrurnlenac ophthalmic solution) 0.09%. administered
`twice daily. was approval Dy the Food and Drug Almlnlstrar-on
`(FDA) on Fbrch 24, 2005 for the treatment of patients vilth posi-
`cataract ocular
`iriflamrnation,
`and in January 2006 for
`the
`trealment of ocular pain folbwing cataract surgery‘
`' Bromday’°' (hroinlenac ophthalmic solution) 0.09% administered
`once d.i'VI was anproved by the FDA on Octolzer 16.
`.2010 for the
`treatment of postoperative inflammation and reducfion of ocular
`paln In patients who have undergone cataract extraction‘
`it Based on extensive post-rnarlceung experience and data from
`clinical trlals, bmmlenac aphmalrmc solution has iiemonsuated a
`favorable safelv nrofila
`intraocular
`<v The
`iriadilletl
`formulation of bromlenac facilitates
`penetration.
`lhetehy alowlng a
`lower medication load while
`inaintaormg clinical emcacy with once daily dosing
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`5
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`1'reattnentPhaae: Day -I tn Day 1.5
`- subjects began dosing on Day A (~ 24 hours belore surgery)
`vsuhlecn returned tn the offia on Day I liar evaliatlenol safety
`and alncacy
`flohjecte returned to the amine on Day St: hr evaluetlen el
`lately and elfiocy
`-scnjects returned tn the office on Day 3:: lot einlintlon cl
`eiely and efliccy
`-Dlsizenllmzed lest awn! on day 14 and subjects returned to the
`
`lollew-up Phase: Dav 22+: or 74»: Day: After riiul Doea
`- silfieets nlumedtn the elllce on Day 12+: or 7+3 days alter
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` 6 To evaluate the effucacy and safety of low-concentration, modified
`hrornfenac stadium opnuialrnk solution dosed once oallv for the
`treatment of ocilar inflarrimauoii and ocular pain associa@ wilh
`cataract
`surgery in subjects who have undergone cataract
`extraction with posterior chamber inn-aocular lens implantation
`
`Preeerrtol at the 20!: Ana el Fleeting ol the Areevicee Acetic-y ol ophthalmology, Mairenler 10-13, 2012, Chicago. IL
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`Mike on Day 15:1. for evaluation elaelety and effiuey
`smre
`diseontiiuation of ten agent (or term ination evaluatim
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`Page 1 of 1
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`SENJU EXHIBIT 2227
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`LUPIN V. SENJU
`
`IPR2015—01l00
`
`LZ6178Z0'|Ohld