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............

....c.CIIIieIl.......

a..a" seel t.""J.'I:t?l

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lOt." 126(40.1)

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C....ton,.~BCOtIc(cIpro ~ ....,......... otIe.........>, CIpndId (cIpro• .aa13" 7•••7••••~l%)'"OtIc..........N....,............,., JIycInot........ OtIc....... (PNB) .

AIIfaeuIIl..".ve4- pIOCIucts. CipreCa }fC.Otic (eiplOt1oueia~..~_ nsion),Ci (eipNftoxMiiaO.3%Ind ...........O.l%)SttIiIt Otic S nor Neomycin SulfiaI_.PoIyayxiB B W,. IIMINyclleaclRiloalOtic SoIuliM Wappmral ...... OIl fht~ ofhodl1hoir ia ..~~ It was pr•••"'''' hie --. .rCipo·He 1114CiprodG· .. - propatia ....efIiotef piCl..e.. is · .....

In .q.....-lem_ ..........".of...... IU.......trialswith......1...._.ldetal3 topicaI~__.._~......~were" for1btfollow" Iftti..micIebia VI pll•••, YI.~......_biotic VI ............ 1fttibiode, sIII'Oid YS ......~...._~vs-.w....fOIcJef ...........syseemadc NY_ oItopica1 for AOE .. putof.~,CY~e _a .,..~AI"I.,oro..~I "'~s.pr, , (M().}fNSf).ThIir"WIII_....,,~_....i u .u <RCTs) IIlry ..,i_.of...siD by 1IItiIIi•.uy pooIiaa studill. Dac.ipdw 20rIft tIWs·iMWId ill the fiMI ill V..ofpuW__ hat 1961 to 200'~witIl $0%of pUffs••••1"'_2'% ift2002 .

J ..n •o........... W~II"'''''''S._. ; si.....01.... 11 I.......... .,............. 01•..,••••• 1G06: IJ4SM ...

,

---:....-1 Page(s) ofCopyright Material

have been Withheld from thisPortion of the Review. .

MediIIl~T_t.der...WilI_ M. Be14. M.:D.NDA21 AZ -9f!!!!l( .J.~()~

In the prececliftl topical quinolonc _tHetie Ihd tepialno.....inoloM ....ioticadtitvod diitical QR raIf:S for AOE .3 tID" days. 1 tID 10 cMys. and 14 to 21cays. QUloIonos usedin"~..weN o8DJuleill (I stu4y). c.....in atoM (J),or cipl'etloucia COIIIbinIcI with dlrumethMoM (2) or~ (I).

In the "..-dina.... topieal antimiaoWallsIImW.. topieaI aalimiaobilllllonlldaievwcomp....cliDiealllld hMtaioIoaic cure" fOr AOlaa1 days. MOst studia wae sinalebliRcl, oflow quIIi.,." perfomaed ..... toilet. ~-.oidco.i -inthe ... _tysa WON ciproftouciNby~ciproftoucinldeulftllh and...ic.~.ConqMnbIe- cliDiell....occur widt....,. VI~41"" YS inolone_til*Jdl. _1IIIiIaicrehiaI vs .............. srerow; seeroid outGOmeSdIM ......pIus~. ...,. Sid..of~CUN"to "-_clinicalresponse, with..10% to 9S"~ eft1aIy .......ofan visit. QuiRoIonahaft sliJlitly hettlrlMloterioloaie eftlcMy ....~MbDiolies.

- -

CiploftexMia. ,".......... showft 10..hi....,••tiv. r.__ oMisoxtlma; whWlsupports the -siftI1c cliftical trialsu~ ill-dais IppIica&ioA • Mil u the 1M 011

....1DA's,.........ofSlfay freretiy.... fbrCi~·HCOIic(e ..h~..1t~otie ..., ) ..CiprodlrJl· (cipro O.J%1IMI~O.I%)Sterile~~

In ctUakII SIudJ CftOT-ttV OJ IA 02, -~Per~ (MPP).......... 174,._ht"trllllM8t (1O%and-12%or.~"~1[~.......for cl _,..,..,. """'yciJIIhy~lft.[PNH)...........vel)') at..OM ,..110,.. ,..thas..,. Thct below of_.........., -kte8tifled ill die MPP po' i ' ........-..-.~of (l7%ia c ..,_~ift..PNH....).~ wu l"' iD ...~iapNp.. l1% JlNH..-,...pIN '-1' _.1 in Mm'popuIatiost... siMI MPP po, dlalE.

wtMn, ."c. 'Ii,.1' .-.1 ......................- i widlotilia ......

4 MPP.a••IIlliIR 0P VWlI '.1 ,............a a'~.h.rnll rllil' .. I1· ' II_a 11I u,.S...d.6alll_)"- V'1iiIJ'"V" ...

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(CLSI) _ automll.d Vilik TM m~ plMl.1IladcIieion" ..,. the sesitlYily of.... · to cipIoftouoin-.a

____ ~·speeifieallyfor this saudy (tile cipfotIouc series) to

......1M MIC efcipreftoxacia _ada were "lOdetenItiMthe MICSO _MIC9O ofciploflouein for So , •.,."....

The MIC MICte ofcipmftouein IN shown itt '-d below. Thn weN no<Ii in MlC Ntweea i...fiOID pIItieMI • ChI eiprofIeuciit poup _ .... fNIII,... ia eM J'NHpou,. f.P.~ dMtMlC!O ofciplotloxaria.-0.12NI"......MlCto WM 0.'0 N/mL. 'or So .,." Ibe M1C!O lWIf· 0.2$ JIWmLand the M1Cto wu 1........

T.... 4: CIpn....MIC....MlC. (JW1d.) for Ie ..............s. ..,.". ..MITT........

8eGeIrio.,.... is .............·ia ...... JlftWicW btiow.1adIe~ PerPrdocol ,.......(MPP). atlMJch the EnIkll·TU (EOT) visit _ ....T...-..c_visit,which·~ alIout OM w_k... lOT, die ,.,..wu ......... 01'

PNsumeIIErIliIio.fortM..~tyof"""ia"""'''''pe... At_lOTvi.""".' ·i. the eiprofloxMin.....93% ill tile PNH pup'" Ihd...-Praudt .

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8. Safety

Fer ...... satety ia on Clinial TtWCIPRor 111/ OJ IA 02; ..dw,....0fIicw Review April 1, 2006.

1111_ r..... ill Ciiaieal TrW ClPROT,1II OJ IA 02 ...........JIIO"ided 1It.~ 1ftlUP;"~ (51%)of""""'''midi fOr1 .,.aW in .... JIftJIICOI. In die PNH...., ...........,of..'. IS(64%) .., Aw'.ys.

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Medial~1'..Ladlrl.wiIwWnu. M. Boy, M.D.NDA 21-911 AZCft!l(~••_,.

In the... pIOvidld-bolow, ,....WillI to .........~ OOOUfNc1in' (1.6%) pIItients in cipfo.......and 4 (1.3%)'"in the PNH poup itt Oi Trial CIPltOT DJI 03 IA 02. Most0'''''~acIv... nt8GtionI to discontiftutIti i..... cipftJfloXleiapoup weN advtne raeUonsiIlvolvilla tho ar.

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TIle _ .. raGtioal~in Clinical Trial CIPRO'I' WI 031A OJ.. fauIMl·ift ........................ dtiirniew. T1bIo7: C_T__• Adv...1-.SIIfIty Iveats 0CcwriB. in at Last 2%ef...... ia £ 1 .....0-"."S,.... "'lei",.......

9. AdYiIory COIDlIlitt..Meetlaa

16

MI6II~T_~""wu. M. Boy4. M.D.NDA21-91a.u~~••_,,1)"9~.

10. Pediatrics

1'hc safety aM 8ft'ectiv_ ofCanxal in iar-ts below one yarof. have BOt .,..tstabIiIW. The cfIIolIey ofCotrual in .....otitis...in po4iIarie pIIientI_ y..orolder his been d_8~·ia.C0IItft)I" Glinical &rial.

'I1tleN is DO..... that the ode adaIUaisntion ofquineloMs his aD)' dr. OIl wei....beariftljoiJds, IV. tIIouIft systemic *inistladoa ofS01MquiReloMs has .,.. shown tocause MthIoJ*hy ininulllture.... .

11. Other ae.ev·_t Replatory Issues

OSIA Divisionof~mv""'" (OSI) audit was ........d.

Per" OSI rev_'"F~ 1,2006:

".. Revin' Diviiiea,........routiM..audit ia.letioft oftwo -.ely sills tMtceaducted s&udy ProIocollClJlltOf mIA 02..m.........w.- ..........1UppOftofNDM2I·'II.

• -a .. 1 '2. .NA/-NiJ tIhIiiiIltitttJ-...""""... DtItt#.", .yAJ-Ml....~~"..N DI1M~

.....0Il .......1tsof"~ it ..'IllS in IUPIIOfI ofthis

..,licatioftfiuM Dr. GoI4I&eift'i s&udy .... ii ' ....

........ _ Dr. ChMpUIts-..ty., pa_.....

..iIitioM ......

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1G04..- ef.hil)' 1). n.cl." n (eRe).........MjlctID....J ....., .. July 6, 1CMM.

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