`RCT EX. 2089 - 1/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 2/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 3/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 4/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 5/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 6/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 7/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 8/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 9/18
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`
`
`Lacosamide pharmacokinetics
`
`Cawello eta!.
`
`A
`
`B
`
`c
`0
`~
`'E Q)
`(,) c
`0
`0
`C'O
`E
`C'O a:
`:E
`~
`
`(/)
`
`6
`
`~2_o_o_m_g __ L_oa_d_i_ng __ D_o_se ________________ ~ __ __.
`10 days
`
`00mg
`12
`Titration Regimen
`
`50/100 mg BID oral
`-
`----- 200 mg IV loading dose+ 100 mg BID oral
`
`0
`
`24,
`
`48
`
`72
`
`96
`
`120 144 168 192 216 240 264 288
`Time (h)
`
`- - - 200 mg oral loading dose + 100 mg BID oral
`
`0
`
`24
`
`48
`
`72
`
`96
`
`120 144 168 192 216 240 264 288
`Time (h)
`
`Figure 2. Simulation of plasma concentration-time profiles of single LCM 200 mg IV (A) or oral (B) loading dose followed by oral
`LCM 100 mg BID initiated 12 h after start of infusion compared with an oral titration regimen of LCM 50 mg BID (100 mg/day)
`for 1 week followed by LCM 100 mg BID (200 mg!day). BID, twice daily; IV, intravenous; LCM, lacosamide.
`
`established that switching patients from the oral
`LCM formulation to an IV LCM infusion followed
`stable and predictable pharmacokinetics. 56,61 This
`was shown by the AU C ratios for IV to oral LCM ap-~
`pro aching 1 OOo/o, indicating comparable L~Mexp"o~
`sure between the IV infusion and_orat'tW.ttments. 61
`Overall, the bio~valen:Ceb~tween oral (tablet
`and oral§_olutioll) and IV LCM offers the advantage
`________ of~direct conversion among the three formulations
`without the need for dose titration adjustment in
`patients with focal epilepsy (Table 2).25,26,56,6 1
`
`Loading dose
`For adults with focal epilepsy whose seizures are
`not controlled with their current therapy, achieve(cid:173)
`ment of an effective AED dose as quickly as pos-
`
`sible after initiation of adjunctive treatment could
`be importa~. 55 Initiating LCM therapy with a sin(cid:173)
`gle l9adirfg dose of 200 mg, followed ,..., 12 h later
`by~ioo mg BID (200 mg/day) maintenance dose
`regimen, is approved in Europe and is an alter(cid:173)
`native method for initiation of adjunctive LCM
`treatment within the currendy approved indica(cid:173)
`tion when the physician determines that rapid at(cid:173)
`tainment of LCM therapeutic plasma con centra(cid:173)
`tion and therapeutic effect are warranted. 26 (At the
`time this article was written, use of LCM 200 mg
`as a loading dose was not approved by the U.S.
`FDA.) Use of a loading dose to quickly achieve
`an effective dose of an AED may be desirable for
`patients whose seizures are not controlled with
`their current therapy, patients with a risk of or
`
`24
`
`Ann. N.Y. Acad. Sci. 1329 (2014) 18-32 © 2014 New York Academy of Sciences.
`
`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 10/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 11/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 12/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 13/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 14/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 15/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 16/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 17/18
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`Argentum Pharm. v. Research Corp. Techs., IPR2016-00204
`RCT EX. 2089 - 18/18
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