Ware, Jacqueline Hm
`
`From:
`Sent:
`'
`;
`subject:
`
`Ware, Jacqueline H
`Monday, May 19, 2008 5:10 PM
`'Blumberg Alan'; 'DOttavio Misty'
`Sullivan, Matthew; Ware, Jacqueline H
`Question about LCM
`
`Dear Alan,
`Can you please assist with the following question? If Schwarz has already submitted this
`information, please just let me know where/when it was submitted.
`
`. Has Schwarz submitted additional information on the nephropathy of subject #588/8061?
`
`We believe this information was requested 2-3 weeks ago. However, I searched Misty's list of
`requests/responses to see if i could find it and was not successful.
`
`Thanks,
`Jackie
`>l<*3:**********************************************
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research, FDA
`10903 New Hampshire Avenue; W022 Rm. 4348
`Silver Spring, MD 20993—0002 _
`
`ine: 301-796-1160
`ldX: 301-796-9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`it may contain information that is protected, privileged, or
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`confidential, and it should not be disseminated, distributed, or copied to persons not authorized to receive such information.
`lf you are not the
`intended recipient, any dissemination, distribution or copying is strictly prohibited.
`If you think you have received this e-mail message in error,
`please e-mail the sender immediately at jacqueline.ware@fda.hhs.gov.
`
`

`

`Ware, Jacqueline H
`
`Page 1 of2
`
`From: Ware, Jacqueline H
`
`Sent:
`
`Monday, May 19, 2008 2:10 PM
`
`'Blumberg Alan'; 'DOttavio Misty'
`
`Cc:
`
`Sullivan, Matthew; Ware, Jacqueline H
`
`Subject: RE: Clarification request RE: FDA Request for information - NDA 22-253, 22-254_ M May 12,
`2008
`
`Wei
`
`.
`Dear Alan,
`The clinical team has considered your proposals and had determined that they would like Option 2.
`
`On a separate note, l believe that I sent a request about the exposure to placebo in the epilepsy population, (including those pts
`exposed 'to placebo while randomized to LCM) a couple of weeks ago. Do you recall such a request and, if so, have you sent a
`response?
`
`Thanks,
`Jackie
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander,- United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`
`Center for Drug Evaluation and Research, FDA
`10903 New Hampshire Avenue; W022 Rm. 4348
`S‘
`fipring, MD 20993-0002
`
`phone: 301-796—1160
`fax: 301-796-9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`It may contain information that is protected, privileged, or confidential, and it
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`should not be disseminated, distributed, or copied to persons not authorized to receive such information.
`If you are not the intended recipient, any dissemination,
`distribution or copying is strictly prohibited.
`If you think you have received this e-mail message in error, please e—mail the sender immediately at
`jacqueline.ware@fda.hhs.gov.
`
`From: Blumberg Alan [mailto:Alan.Blumberg@ucb-group.com]
`Sent: Friday, May 16, 2008 5:34 PM
`To: Ware, Jacqueline H; Sullivan, Matthew
`Cc: DOttavio Misty; Moe Kirsten
`Subject: Clarification request RE: FDA Request for Information - NDA 22-253, 22-254, -————- May 12, 2008
`
`This message contains an encrypted email which can be read by opening the attachment
`
`SCHWARZ BlOSClENCES, lnc.
`A Member of the UCB Group
`,
`
`Mail PO. Box 110167 - Research Triangle Park - NC 27709 - USA
`\fia Courier 8010 Arco Corporate Drive - Suite 100 — Raleigh - NC 27617 - USA
`Phone +1 919 767 2555 - Fax +1 919 767 2570 - E-mail info@schwarzgharma.com
`
`5/27/2008'
`
`

`

`Page 2 of 2
`Legal Notice: This electronic mail and its attachments are intended solely for the person(s) to whom they are addressed and contain information which is
`confidential or otherwise protected from disclosure, except for the purpose for which they are intended. Dissemination, distribution, or reproduction by anyone other
`than the intended recipients is prohibited and may be illegal. if you are not an intended recipient, please immediately inform the sender and return the electronic
`mail and its attachments and destroy any copies which may be in your possession. UCB screens electronic mails for viruses but does not warrant that this
`electronic mail is free of any viruses. UCB accepts no liability for any damage caused by any virus transmitted by this electronic mail. (Ref: #*Bl1107)
`WWW—mm“
`
`.
`
`/_\
`
`5/27/2008
`
`

`

`Ware, Jvaueiine H
`
`Page 1 0f 2
`
`From: Ware, Jacqueline H.
`
`Scot:
`
`Monday, May 19, 2008 1:38 PM
`
`'Biumberg Alan'; 'DOttavio Misty’
`
`Cc:
`
`Sullivan, Matthew; Ware, Jacqueline H
`
`Subject: FW: Partial Response to FDA Request for information - NDA 22—253, 22-254
`
`Dear Alan,
`Thanks for clarifying. This response is clear.‘
`Jackie
`*************************************************
`
` - May 12, 2008.
`
`BQAE
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research, FDA
`10903 New Hampshire Avenue; w022 Rm. 4348
`Silver Spring, MD 20993-0002
`
`phone: 301-796-1160
`fax: 301-796—9842
`
`email:
`
`jacqueiine.ware@fda.hhs.gov
`
`it may contain information that is protected, privileged, or confidential, and it
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`shr
`‘ ~ot be disseminated, distributed, or copied to persons not authorized to receive such information.
`if you are not the intended recipient, any dissemination,
`d
`an or copying is strictly prohibited.
`if you think you have received this e-mail message in error, please e-mail the sender immediately at
`jat
`.ie.ware@fda.hhs.gov.
`
`
`
`From: Blumberg Alan [mailtozAlan.Blumberg@ucb—group.com]
`Sent: Monday, May 19, 2008 1:19 PM
`To: Ware, Jacqueline H, DOttavio Misty
`Cc: Sullivan, Matthew, Moe Kirsten
`Subject. RE: Partial Response to FDA Request for Information- NDA 22-253, 22-254 ’——-——-
`Importance: High
`
`May 12, 2008
`
`Egg}
`
`Dear Jackie,
`Please see if the attached clarifies the situation for the Clinical Reviewer.
`Best regards,
`Alan
`
`if not, perhaps we should set up a short telecom?
`
`
`
`From: Ware, Jacqueline H [mailto:jacqueline.ware@fda.hhs.gov]
`Sent: Friday, May 16, 2008 4:12 PM
`To: Blumberg'Alan; DOttavio Misty
`Cc: Sullivan, Matthew
`Subject: FW: Partial Response to FDA Request for Information - NDA 22-253, 22-254. A—May 12, 2008
`
`fiflfi)
`
`Dear Alan,
`The clinical reviewer has asked for clarification regarding your recent partial response to our May 12, 2008 requests. Please see
`below.
`
`The original request refers to concomitant medications and diseases at baseline before entering the studies. The sponsor's
`table EP 5.1.1 is entitied:"medications taken during the baseline phase in population pool 81". it is unclear whether this
`
`5/27/2008
`
`

`

`table refers to medications t entm or to medications taken during the placebo--controlled period ("baseline phase") which
`(would include baseline plus new medications taken during the placebo—controlled period). Similarly, EP 5.1.2 refers to
`concomitant diseases
`
`Please clarify that these tables refer to the baseline use of medications and diseases.
`
`Thanks,
`Jackie
`*******************************************§<*****
`
`/“‘
`
`Page 2 of 2
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research, FDA
`10903 New Hampshire Avenue; W022 Rm. 4348
`Silver Spring, MD 20993-0002
`
`phone: 301-796-1160
`fax: 301-796—9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`It may contain information that is protected, privileged, or confidential, and it
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`should not be disseminated, distributed, or copied to persons not authorized to receive such information.
`if you are not the intended recipient, any dissemination,
`distribution or copying is strictly prohibited.
`If you think you have received this e-mail message in error, please e-mail the sender immediately at
`jacqueline.ware@fda.hhs.gov.
`
`From: Blumberg Alan [mailtozAlan.Blumberg@ucb—group.com]
`Sent: Friday, May 16, 2008 2:15 PM
`To: Ware, Jacqueline H, Sullivan, Matthew
`,
`Cc: DOttavio Misty; Moe Kirsten
`Subject: Partial Response to FDA Request for Information - NDA 22-253, 22~254, m May 12, 2008
`
`'
`
`.-
`3&4?
`"
`
`Dear Jackie,
`Please find attached a partial response to the request made on May 12 in a WORD document. Responses to questions 2, 3 and
`4 with tables to support the responses 2 and 3 are included.
`
`Best regards,
`Alan
`
`5/27/2008
`
`

`

`
`
`*Ware, Jacqueline H 'M
`
`
`
`From:
`Sent:
`
`-
`
`oubject:
`
`' Dear Alan,
`
`Ware, Jacqueline H
`Friday, May 16, 2008 5:04 PM '
`'Blumberg Alan'; 'DOttavio Misty'
`Sullivan, Matthew; Ware, Jacqueline H
`FDA Request for Information - NDA 22-253, 22-254
`
`-
`-———-_.
`
`hi4)
`
`Attached are several additional requests from DNP's clinical team for lacosamide. Like other
`requests, you may respond'via email and follow up with an official submission.
`
`. Please comment on the apparent dose response in the treatment emergent use of analgesics
`(including opiates), anesthetics, psycholeptics, systemic corticosteroids, muscle relaxants, cough
`and cold preparations, beta blocking agents, calcium channel blockers and agents acting on the
`renin-angioetensin system in EP 82 (as per Table EP 4.1.4).
`
`. Please comment on whether PR prolongation or adverse cardiac events occurred with
`concomitant use of beta-blockers or calcium channel blockers with LCM.
`
`We request that you submit this information by May 20, 2008, if possible.
`
`Thanks,
`Jackie
`
`APPEARS This WAY
`Git ORiGlNAL
`
`

`

`Ware, Jacqueline H
`
`From:
`
`Blumberg Alan [Alan.Blumberg@ucb-group.com]
`
`smt:
`
`Friday, May 16, 2008 4:57 PM
`
`Ware, Jacqueline H
`
`Page 1 of 2
`
`.
`
`'
`
`Subject: RE: Partial Response to FDA Request for information - NDA 22-253, 22-254, *\
`
`ay 12, 2008
`
`bid.)
`
`I have sent this clarification back to the team for a response. Have a nice weekend, Jackie.
`clarification in a few minutes, as it is only fair. ©
`
`I will be sending you a question for
`
`-----Original Message-«~—
`From: Ware, Jacqueline H [mailto:jacqueline.ware@fda.hhs.gov]
`Sent: Friday, May 16, 2008 4:12 PM
`To: Blumberg Alan; DOttavio Misty
`Cc: Sullivan, Matthew
`Subject: FW: Partial Response to FDA Request for Information - NDA 22-253, 22-254, m flay 12,
`2008.
`
`b 4
`g 3
`
`Dear Alan,
`The clinical reviewer has asked for clarification regarding your recent partial response to our May 12, 2008 requests.
`Please see below.
`
`.
`
`The original request refers to concomitant medications and diseases at baseline before entering the studies. The
`sponsor‘s table EP 5.1.1 is entitled:"medications taken during the baseline phase in population pool 81". it is
`unclear whether this table refers to medications at entry or to medications taken during the placebo—controlled
`period ("baseline phase") which (would include baseline plus new medications taken during the placebo-
`controlled period). Similarly, EP 5.1.2 refers to concomitant diseases.
`Please clarify that these tables refer to the baseline use of medications and diseases.
`
`Thanks.
`Jackie
`*************************************************
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research, FDA
`10903 New Hampshire Avenue; W022 Rm. 4348
`Silver Spring, MD 20993-0002
`
`phone: 301-796-1160
`fax: 301-796—9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`It may contain information that is protected, privileged, or
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`confidential, and it should not be disseminated, distributed, or copied to persons not authorized to receive such information.
`If you are not the intended
`recipient, any dissemination, distribution or copying is strictly prohibited.
`If you think you have received this e-mail message in error, please e-mail the
`sender immediately at jacqueline.ware@fda.hhs.gov.
`
`From: Blumberg Alan [mailtozAlan.BIumberg@ucb-group.com]
`Sent: Friday, May 16, 2008 2:15 PM
`To: Ware, Jacqueline H; Sullivan, Matthew
`Cc: DOttavio Misty; Moe Kirsten
`Subject: Partial Response to FDA Request for Information ~ NDA 22-253, 22-254, u
`
`
`
`@643
`
`Vlay 12, 2008
`
`Dear Jackie,
`
`5/27/2008
`
`

`

`Please find attached a partial response to the request made on May 12'In a WORD document. Responses to questions
`2, 3 and 4 with tables to support the responses 2 and 3 are included
`
`Page 2 of 2
`
`Best regards,
`Alan
`
`
`
`SCHWARZ BIOSClENCES, Inc.
`A Member of the UCB Group
`Mail PO. Box 110167 - Research Triangle Park - NC 27709 - USA
`We Courier 8010 Area Corporate Drive - Suite 100 - Raleigh - NC 27617 — USA
`Phone +1 919 767 2555 - Fax +1 919 767 2570 - E-mail info@schwarzpharma.com
`
`Legal Notice: This electronic mail and its attachments are intended solely for the person(s) to whom they are addressed and contain information which is confidential or
`othenNise protected from disclosure, except for the purpose for which they are intended. Dissemination, distribution, or reproduction by anyone other than the intended
`recipients is prohibited and may be illegal. if you are not an intended recipient, please immediately inform the sender and return the electronic mail and its attachments and
`destroy any copies which may be in your possession. UCB screens electronic mails for viruses but does not warrant that this electronic mail is free of any viruses. UCB
`accepts no liability for any damage caused by any virus transmitted by this electronic mail. (Ref: #‘Bl1107)
`
`5/27/2008
`
`

`

`Ware, Jacqueline H
`
`Page 1 of 1
`
`From: Gunther, Sheryl
`
`Sent:
`
`Thursday, May 15, 2008 7:21 PM
`
`Hershkowitz, Norman; Ware, Jacqueline H
`
`Subject: Vimpat (lacosamide)
`
`Hi Norman and Jackie:
`
`We have received all of the domestic and foreign clinical inspection results, albeit in some cases we only have a summary of
`findings and are waiting to receive the full reports with exhibits. The sponsor inspection is startingon Monday. My supervisor
`would like to wait for the findings from the sponsor inspection before signing off on the Clinical Inspection Summary for this
`application. We should have the sponsor inspection results by late May, or at the very latest, the first week in June.
`
`Is this all right?
`
`Thanks,
`Shag/56W
`
`Sheryl D. Gunther, R.Ph., Pharm.D.
`LCDR, US. Public Health Service
`Senior Regulatory Review Officer
`Good Clinical Practice Branch 1
`Division of Scientific investigations
`Office of Compliance
`'
`Center for Drug Evaluation and Research
`Food and Drug Administration
`10903 New-Hampshire Ave., Bldg. 51, Rm. 5330
`Silv"r Spring, MD 20993
`C
`°hone: 301 -796-3386
`
`E.
`
`sheml.gunther@fda.hhs.gov
`
`5/27/2008
`
`

`

`Ware, Jacqueline H
`
`'Page 1 of1
`
`From:
`
`that:
`
`Ware, Jacqueline H
`
`Monday, May 12, 2008 10:59 AM
`
`'
`
`'Blumberg Alan'; 'DOttavio Misty'
`
`Cc:
`
`Sullivan, Matthew; Ware, Jacqueline H
`
`Subject:
`
`Additional Lacosamide Injection and Solution CMC IR Comments
`
`importance: High
`Attachments: lacosamideCMClR#3.doc
`
`Dear Alan,
`
`In the attached WORD document, please find several additional requests from the chemistry review team for
`lacosamide. Like other requests, you may respond via email and follow up with an official submission.
`
`We request that you submit this information by May 16, 2008, if possible.
`
`Thanks, Jackie
`
`*************************************************
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`C
`for Drug Evaluation and Research, FDA
`1b- -J New Hampshire Avenue; W022 Rm. 4348
`Silver Spring, MD 20993-0002
`
`phone: 301-796-1160
`fax: 301-796-9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`it may contain information that is protected, privileged, or confidential, and it
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`should not be disseminated, distributed, or copied to persons not authorized to receive such information.
`If you are not the intended recipient, any dissemination,
`distribution or copying is strictly prohibited.
`If you think you have received this e-mail message in error, please e-mail the sender immediately at
`jacqueline.ware@fda. hhs.gov.
`
`5/27/2008
`
`

`

`NDA 22-254 M'WM
`
`hi5?
`
`CMC IR #3
`
`Comments for NDA 22—254 {solution for infusion)
`
`l. The diluent compatibility data indicates an incompatibility between the drug product and the
`dextrose diluent. The impurity contents associated with RT “9" and RT —- t exceed the
`ICH qualification limit based on your proposed maximum daily dose. Provide justification for the
`use of the drug product with the dextrose diluent.
`Include in your justification the identity of the
`impurities identified by RT "237’
`and RT --= as well as data demonstrating their safety for
`
` V; _.
`use in humans.
`
`77
`//
`
`

`

`Ware, Jacqueline Hm
`
`From:
`Sent:
`'
`
`subject:
`
`Ware, Jacqueline H
`Monday, May 12, 2008 10:38 AM
`'Blumberg Alan'; 'DOttavio Misty'-
`.
`Sullivan, Matthew
`FDA Request for Information — NDA 22-253, 22-254, kw
`
`fiifig
`
`Attachments:
`
`LCM .May 12.doc
`
`Dear Alan,
`In the attached WORD document, please find several additional requests from DNP's clinical team for
`lacosamide. Like other requests, you may respond via email and follow up with an official submission.
`
`We request that you submit this information by May 16, 2008, if possible.
`
`Thanks,
`Jackie
`*************************************************
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research, FDA
`10903 New Hampshire Avenue; W022 Rm. 4348
`Silver Spring, MD 20993—0002
`
`nhone: 301-796-1160
`' 301-796-9842
`
`ail:
`
`jacqueline.ware@fda.hhs.gov
`
`it may contain information that is protected, privileged, or
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`confidential, and it should not be disseminated, distributed, or copied to persons not authorized to receive such information.
`If you are not the
`intended recipient, any dissemination, distribution or copying is strictly prohibited.
`if you think you have received this email message in error,
`please e-mail the sender immediately at jacqueline.ware@fda.hhs.gov.
`
`LCM May 12;doc
`(32 KB)
`
`

`

`May 12, 2008. Request for information for LCM.
`
`1)
`
`Please provide the total number of subjects screened and the total number of
`subjects who did not fulfill eligibility criteria for the placebo—controlled epilepsy
`studies. Provide the reasons for which these patients failed eligibility criteria.
`The following format is provided as an example.
`
`
`
`
`
`
`
`
`
`Entered studies
`
`Did not fulfill eligibility criteria
`_ Concomitant disease
`
`Uncontrolled hypertension
`Elevated LFT
`Elevated creatinine
`Etc.
`
`Protocol exclusionary medication
`Antipsychotics
`Benzodiazepines
`Etc.
`
`Etc.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`2)
`
`3)
`
`4)
`
`Provide a summary table of all baselineconcomitant medications in the EP 81, by
`treatment group (similar to Table 4.1.1, but including all medications, not only
`medications taken by 10% of patients).
`
`Provide a summary table of all baseline concomitant diseases in the EP 81 pool,
`by treatment group (similar to Table 5.1.1, but including all diseases, not only
`those presented by 5% of patients).
`
`The intravenous (IV) phase 2/3 epilepsy studies recruited patients from the open
`label oral tablet studies. Please clarify what were the criteria for selection of
`patients for the phase 2/3 IV LCM studies.
`
`5)
`
`Provide a summary table of all baseline concomitant diseases and concomitant
`medications taken by patients in the IV phase 2/3 LCM studies.
`
`

`

`Ware, Jacqueline HM
`
`. From:
`Sent:
`
`.
`subject:
`
`v
`
`Ware, Jacqueline H
`Wednesday, May 07, 2008 7:38 PM
`'Blumberg Alan'; ‘DOttavio Misty'
`Ware, Jacqueline H; Sullivan, Matthew
`FDA Request for Information - NDA 22-253, 22-254, A
`
`h“?
`
`Dear Alan,
`Attached are several additional requests from DNP's clinical team for lacosamide. Like other requests, you
`may respond via email and follow up with an official submission.
`
`0 The following patients discontinued from the open label epilepsy studies due to either cardiac disorders or
`ECG investigations.
`
`667010502
`667016937
`755122402
`755108404
`
`Please provide the narratives and CRFs for these patients. If this information has been submitted, direct
`the reviewer to the exact location in the application.
`
`Please also submit the EC65 for Subject 755122303.
`
`Please clarify why Subject # 754/12512, who attempted suicide during the placebo controlled phase of
`study 754 while taking LCM 200 mg/day, was not included in your analysis of suicidality.
`
`.
`
`.
`
`We request that you submit this information by May 19, 2008, if possible.
`
`7
`
`Thanks,
`Jackie
`
`*************************************************
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research, FDA
`10903 New Hampshire Avenue; W022 Rm. 4348
`‘ Silver Spring, MD 20993—0002
`
`phone: 301-796-1160
`fax: 301—796-9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`It may contain information that is protected, privileged, or
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`confidential, and it should not be disseminated, distributed, or copied to persons not authorized to receive such information.
`if you are not the
`intended recipient, any dissemination, distribution or copying is strictly prohibited.
`if you think you have received this e-mail message in error,
`please e-mail the sender immediately at jacqueline.ware@fda.hhs.gov.
`
`

`

`Ware, Jacqueline H
`
`Page 1 ofl
`
`From:
`
`Sullivan, Matthew
`
`'Sont:
`
`Tuesday, May 06, 2008 11:58 AM
`
`Blumberg Alan; DOttavio Misty
`
`Cc:
`Ware, Jacqueline H
`Subject: Environmental Assessment IR 5/6/08
`
`Alan and Misty -—
`
`The reviewer looking at the Environmental Assessment portion of your applications has made a request:
`
`Please submit a non-confidential EA (EAS become public documents once an NDA is approved). The
`submitted EAM You may include any confidential
`information is appendices marked 'Confidential' which will. be removed pn'or to the EA being made public.
`
`fig)
`
`Please let us know when you’ll be able to submit this document.
`Thanks
`Matt
`
`Matthew W.-$u|livan, MS.
`
`Regulatory Project Manager
`Division of Anesthesia, Analgesia
`and Rheumatology Products
`Food and Drug Administration
`P'
`301-796-1245
`FL.
`J1—796-9722 / 9723
`
`matthew.su|livan@fda.hhs.gov
`
`5/27/2008
`
`

`

`Ware, Jacqueline H
`
`From:
`Sent:
`‘
`.-
`subject:
`
`Alan and Misty—
`
`Sullivan, Matthew
`Tuesday, April 29, 2008 11:02 AM
`DOttavio Misty; Blumberg Alan
`Ware, Jacqueline H
`Lacosamide IR 4/29/08
`
`Jackie is out of town this week, so I'm filling in for her. Please find below a request from the DNP team:
`
`Please provide narratives of patients with the adverse event (MedDRA Preferred Term) "dyskinesia" in all Lacosamide
`studies. For the patients with epilepsy, include a description of the type and frequency of seizures the patient had at
`baseline and at the end of the studies. Please send the information no later than Monday, May 5.
`
`Please note that the reviewer made a specific turnaround timeframe request. Please let me know if you aren’t able to meet
`this request. (I believe that the request applies to our advance electronic version, rather than the official lifecycle
`submission.)
`'
`
`Thanks
`Matt
`
`

`

`
`
`:
`
`.
`
`-—-——’
`
`Page<s>Withhe1d
`
`'
`
`I
`
`I.
`
`7
`
`' [1 Tradesecret/ Confidential (b4)
`
`I
`
`Draft Labeling (b4) .
`
`I
`
`'
`
`- Draft Labeling (b5)
`
`___ Deliberative Process :(b5)
`
`

`

`Ware, Jacqueline H
`
`-W F
`
`rom:
`Sent:
`‘
`.
`subject:
`
`' Ware, Jacqueline H
`Friday, April 25, 2008 6:28 PM
`'Blumberg Alan'; 'DOttavio Misty'
`Ware, Jacqueline H; Sullivan, Matthew -
`FDA Request for information - NDA 22-253, 22—254, ———~
`
`b
`
`(4)
`
`Dear Alan,
`Below are several requests from DNP's CMC review team related to their ongoing review of the lacosamide
`applications. Please submit your responses to these requests in electronic archival format as an amendment to
`the above NDAs. It is acceptable for you to email your responses to me in advance of a formal, archival
`submission as long as both communications'(email & archive) contain identical information.
`Comment for All Formulations 1 EDA 22-253, 22-254 ‘ ____
`M‘ ‘3
`4
`
`
`
`1. Provide updated specifications, for both the oral use and parenteral use drug substances, that reflect the M4) :
`revised limit for impurity
`/———— (NM'I "_ . Update the relevant sections of the CTD
`"
`submissions.
`
`Comments for Solution for Infusion w‘ : (NDA 22-254 N
`.
`.
`.
`.
`.
`.
`.
`.
`.
`-
`.
`
`1. Prov1de Justification for omittlng
`in f“ the solutlon for infusmn
`“7‘ _) drug product specifications.
`
`still
`
`2. Provide all available updated stability data for both the solution for infusion
`
`from inverted solution for infilsion samples from the last time point tested
`
`r7fi including results
`
`
`I 3. Revise the primary and secondary container labels N
`M. -
`'
`
`Comment for Solution for Infusion Formulation l NDA 22-254)
`
`1. Explain why the BPR does not document that the water for injection used in each batch meets the
`
`standards established for the drug product. Also explain why the in-process control
`not clearly recognized in the BPR.
`
`is
`
`—
`13(4)
`
`9(4)
`
`@3141}
`
`:
`
`bflfil
`
`/ / / //
`
`1
`
`

`

`
`
`
`
`CMC & Nonclinical Review Comment (flDA 22-254
`
`"“‘W‘x
`
`-
`
`kW
`
`1. Provide the full report of the rabbit pharmacokinetics study (Study no. 1106) referred to in your recent
`
`submission (4/4/08) and demonstrate that the impurity
`‘ ould have been present ‘a—
`/ in rabbits treated with lacosamide during the embryofetal development study at levels greater
`than or equal to those anticipatedin humans receiving lacosamide formulations containing the impurity
`at the proposed specification limit.
`
`M1
`
`Thank you,
`Jackie Ware
`*************************************************
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United StatesPublic Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research, FDA
`, 10903 New Hampshire Avenue; W022 Rm. 4348
`Silver Spring, MD 20993-0002
`
`phone: 301-796-1160
`fax: 301-796-9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`

`

`It may contain information that is protected, privileged, or
`This e-mail message is intended for the exclusive use of the recipient(s) named above.
`confidential, and it should not be disseminated, distributed, or copied to persons not authorized to receive such information.
`If you are not the
`intended recipient, any dissemination, distribution or copying is strictly prohibited.
`If you think you have received this e-mail message in error,
`- please e-mail the sender immediately at jacqueline.ware@fda.hhs.gov.
`
`APPEARS THES WAY
`0N OREGINAL -
`
`'
`
`

`

`Ware, Jacqueline HW
`
`From:
`Sent:
`:
`..
`Subject:
`
`-
`
`Alan,
`
`Ware, Jacqueline H
`Friday, April 18, 2008 7:25 PM
`'Blumberg Alan'; 'DOttavio Misty'
`Ware, Jacqueline H
`FW: Word version of Table
`
`Below is the reviewerls response to your clarification request.
`
`"I would like to see the number of patients who were randomized to placebo plus those who
`were randomized to LCM but received placebo (only) during the initial weeks of the
`titration phase (before starting LCM)."
`.
`
`Hope this helps,
`Jackie
`
`****~k****~k*~k****~k~k*~k***************~k****~k******~k~k
`
`Jacqueline H. Ware, Pharm.D., RAC
`COmmander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research, FDA
`10903 New Hampshire Avenue; W022 Rm. 4348
`Silver Spring, MD 20993—0002
`
`phone:
`fax:
`
`301—796—1160
`301—796—9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`It
`is e—mail message is intended for the exclusive use of the recipient(s) named above.
`ay contain information that is protected, privileged, or confidential, and it should not
`be disseminated, distributed, or copied to persons not authorized to receive such
`information.
`If you are not the intended recipient, any dissemination, distribution or
`copying is strictly prohibited.
`If you think you have received this e—mail message in
`error, please e-mail the sender immediately at jacqueline.ware@fda.hhs.gov.
`
`From: Blumberg Alan [mailto:Alan.Blumberg@ucb—group.com]
`Sent: Thursday, April 17, 2008 6:29 PM
`To: Ware, Jacqueline H
`Cc: DOttavio Misty
`Subject: RE: Word version of Table
`
`Dear Jackie,
`
`I am sorry but my statistician and the team need a clarification of the latest request.
`Kindly ask your Team to guide us on the following question.
`
`"Regarding the request for the number of patients actually exposed to placebo, does the
`DIVISION want
`the count
`(and associated subject years of exposure)
`for subjects who were
`ever treated with placebo regardless of whether or not they also received LCM (ie, for EP
`pool oral formulation,
`this would include subjects who were randomized and received LCM,
`but also received placebo during the Titration Phase)? This would result in some subjects
`being counted in both the LCM and Placebo columns of the table requested (and thus would
`not represent unique exposures). Alternatively,
`is the DIVISION requesting the count of
`subjects randomized to receive placebo who actually received placebo? "
`
`

`

`Thanks for your assistance.
`
`Best regards,
`
`Alan
`
`————— Original Message—————
`From: Ware, Jacqueline H [mailto:jacqueline.ware@fda.hhs.gov]
`Sent: Wednesday, April 16, 2008 9:56 PM
`To: Blumberg Alan
`Subject: Word version of Table
`
`Dear Alan,
`Here you go...
`Jackie
`*********~k***~k***9:***~k********~k***~k*~k**~k*********
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory Project Manager Team Leader
`
`Division of Neurology Products
`Center for Drug Evaluation and Research,
`10903 New Hampshire Avenue; W022 Rm. 4348
`Silver Spring, MD 20993—0002
`
`FDA
`
`phone:
`fax:
`
`301—796—1160
`301—796n9842
`
`email:
`
`jacqueline.ware@fda.hhs.gov
`
`It
`This e—mail message is intended for the exclusive use of the recipient(s) named above.
`may contain information that is protected, privileged, or confidential, and it should not
`be disseminated, distributed, or copied to persons not authorized to receive such
`information.
`If you are not the intended recipient, any dissemination, distribution or
`copying is strictly prohibited.
`If you think you have received this e—mail message in
`error, please e—mail the sender immediately at jacqueline.ware@fda.hhs.gov.
`
`<<Request 4 11 08.doc>>
`
`Inc.
`SCHWARZ BIOSCIENCES,
`A Member of the UCB Group
`Mail P.O. Box 110167 - Research Triangle Park — NC 27709 — USA
`Via Courier 8010 Arco Corporate Drive — Suite 100 — Raleigh — NC 27617 - USA
`Phone +1 919 767 2555 — Fax +1 919 767 2570 — E—mail
`info@schwarzpharma.com
`<mailto:info@schwarzpharma.com>
`‘
`
`Legal Notice: This electronic mail and its attachments are intended solely for the
`person(s) to whom they are addressed and contain information which is confidential or.
`otherwise protected from disclosure, except for the purpose for which they are intended.
`Dissemination, distribution, or reproduction by anyone other than the intended recipients
`is prohibited and may be illegal. If you are not an intended recipient, please immediate]
`inform the sender and return the electronic mail and its attachments and destroy any
`2
`
`

`

`copies which may be in your possession. UCB screens electronic mails for viruses but does
`not warrant that this electronic mail is free of any viruses. UCB accepts no liability for
`any damage caused by any virus transmitted by this electronic mail.
`(Ref: #*BIllO7)
`
`APPEARS THES WAY
`0N ORIGINAL
`
`

`

`
`
`Ware, Jacqueline H .M
`
`From:
`Sent:
`:
`,.
`subject:
`
`Ware, Jacqueline H
`Friday, April 18, 2008 7:18 PM
`'Blumberg Alan'; 'DOttavio Misty'
`Ware, Jacqueline H; Sullivan, Matthew
`FDA Request for Information - Lacosamide NDAs
`
`Dear Alan,
`Attachedis an additional request from DNP's clinical team for lacosamide. Like other requests, you may respond via email
`and follow up with an official submission.
`
`Patients #170106 and # 1701] l discontinued from study SP757 (IV lacosamide) because of adverse events
`of "bradycardia" and "ECG QTc interval prolonged", respectively Please provide copies of all 12-lead ECG
`and ECG reports (not just the ECG interpretations currently includedin the CRFs) for these patients, from
`studies SP755, SP774 and SP757.
`
`Thanks,_
`Jackie
`*************************************************
`
`Jacqueline H. Ware, Pharm.D., RAC
`Commander, United States Public Health Service
`Regulatory P