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`Supplement lo Neur'oa’ogy
`VohIme 62- Number ? - Supplement 5
`
`AMERICAN ACADEMY OF NEUROLOGY
`
`56TH AN NUAL MEETING PROGRAM
`
`
`
`«-
`
`a _‘-’
`
`PROPERTY OF THE
`
` .\JI'.
`
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`finfi NATIONAL
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`LIBRARY or
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`MEDICINE
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`C33
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`LIJ IND
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`C30) 86'27590
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`
`
`IPR2015-00410
`
`Petitioners' EX. 1018
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`Page 1
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`IPR2015-00410
`Petitioners' Ex. 1018
`Page 1
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`
`Poster sessions
`1. Tuesday morning, April 27, 2004
`2' Tuesday afternoon, April 27, 2004
`3. Wednesday morning, April 28, 2004
`4. Wednesday afternoon, April 28, 2004
`,_ Thursda mornin Ann 29 2004
`0'
`y
`g,
`I
`.
`’
`6. Thursday afternoon, April 29, 2004
`
`Special Enhanced Vertical
`.
`lnteg ratlon
`Sunday, April 25, 2004
`1. Session: From Cage to Bedside
`2_ Poster: From Cage to Bedside
`
`Scientific Sessions
`Sunday, April 25, 2004
`1. Neurogenetics and Gene Therapy
`2' Sleep Disorders
`
`A24
`A108
`A192
`A277
`A362
`A457
`
`A6
`A9
`
`A1
`A3
`
`8. Movement Disorders: Parkinson Disease Genetics and
`Epidemiology
`‘
`‘
`.
`.
`0. Neuroepidemiology and-Iiace/Lthnicny
`10' Multiple SCICFOSIS: Imaging I
`1,1' Behavwral Neurology: hanguage
`12. Multiple belei‘OSisz'Clinical TrialsI
`13. Cerebrovascular Disease: Hemorrhage
`14' Epilepsy Surgery
`15. Movement Disorders: Surgical Treatment
`16. Cerebrovascular Disease: Imaging
`17. Dementia Therapy
`
`A88
`A91
`A92
`A95
`A97
`A100
`A102
`A105
`A172
`A174
`
`A176
`18-M0V91‘lem Disorders
`A177
`19. Epilepsy: Imaging
`A179
`20. Multiple Sclerosis: Clinical Trials II
`21. Headache zuid Pain: Migraine Therapy with Triptans A181
`22' Autoimmune Myasthenia
`A183
`23. ALS: Advances in Basic Mechanisms and Treatment A185
`24. Cerebrovascular Disease: Epidemiology
`A187
`25. Behavioral Neurology
`A189
`
`Wednesday, April 28, 2004
`26. Epilepsy: Genetics and Basic Science
`27. Aging and Dementia: Clinical
`28. Movement Disorders: Parkinson Disease Animal
`Models and Lab Science
`29. Multiple Sclerosis: Clinical Trials III
`
`A252
`A254
`
`A257
`A259
`
`Monday, April 20, 2004
`3. Neur -O htlialm lo
`/Ncuro-Otology
`,
`.
`, O p
`0 gy
`4. Child Neurology/Developmental Neurobiology: Cerebral
`Development, Neurocutaneous Syndromes and
`Vascular Disorders
`.
`6. Child Neurology/Dove]opinentzil Neurobiology: Inborn
`Errors 0f Metabolism
`
`1
`
`135(1). genrolosie Mimifgstationspof Systemic Disease
`,
`'
`‘erebrovascular
`iseasc.
`revention
`.
`32. Clinical Epidemiology and Effectiveness Studies
`33' History of Neurology
`31. Movement Disorders: Genetics of Hyperkinetic
`Disorders
`35' Multiple Sclerosis: Genetic Susceptibility
`36. Peripheral Nerve: Molecular Mechanisms and Novel
`A341
`Diagnostic Approaches
`A343
`37. Non Alzheimer Dementias
`TlleSday1 April 27, 2004
`38. Movement Disorders: Parkinson Disease Treatment A345
`A35
`6~ ALS: Biomarkers and Clinical Trials
`39. Cerebrovascnlar Diseas 1: Therapy
`A347
`A86
`7. Mild Cognitive Impairment
`
`
`A15
`
`A19
`
`A21
`
`A262
`A264
`A267
`A269
`
`A271
`A274
`
`Neurology (ISSN: 110028-3878) is published 24 times per year. twice monthly, for the American Academy of NeurologyY 1080 Montreal AVODUO, St Paul) MN 55116, by Lippincott Williams & Wilkins: Inc,
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`Postmaster: Send address changes to Nulll‘lliogy, I’.O. Box 1550, llagerstown, Ml) 217-10,
`
`B5 NEUROLOGY 62 April 2004 (Suppl 5)
`
`11311201500410
`
`Petitioners' EX. 1018
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`Page 2
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`IPR2015-00410
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`Page 2
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`A349
`40. Multiple Sclerosis: Outcomes
`A351
`41. Epilepsy: Antiepileptic Drug Therapy
`A353
`42. Genetic Myasthenia/Myotonias
`43. Headache and Pain: Cluster and Migraine — Treatment
`with Surgery, Herbs and Botulinum Toxin-A
`A355
`
`44 Movement Disorders: Cllorezls
`45. Autonomic Disorders
`
`A357
`A359
`
`Thursday, April 29, 2004
`A424
`46. Multiple Sclerosis: Imaging II
`22:;
`1:; aging and Igelilegtia: IInlaging
`1
`.
`ovement
`isor ers: maging
`A434
`494 Cerebrovascular Disease: Clinical Aspects
`A437
`50. Multiple Sclerosis: Animal Models I
`51, Headache and Pain: Pain Therapy, Receptor Localization,
`Allodynia, Migraine Subtypes and Markers
`A440
`52. Infections/AIDS/Prion Disease
`A443
`.53. Critical Care/Emergency Neurology/Trauma
`A447
`54, Aging and Dementia: Epidemiology
`A450
`1'7. Cl'
`‘ "
`'
`:)
`"TIMI Neumphysfo,1°.gy ‘
`.
`A453
`96. Peripheral Nerve: Clinical btudles
`A519
`57. Aging and Dementia: Basic Science
`A521
`58. Movement Disorders: Parkinsonian Disorders
`A523
`FI).“' ‘:"". 'l‘
`) Lpllepsy Clinical qllldltb
`A525
`60. Multiple Scler051s: Immunology II
`A527
`61. Behavioral Neurology: Memory
`A529
`52- Genetic Myoliauiies
`A531
`
`63. Headache and Pain: Triptan Mechanisms —— Thalamic
`64 CaniTrigenliIlalgiodulatilon -
`’
`.
`‘ere rovascu al‘
`lsease: maglng
`65. Movement DiSOI‘dOTSI HYDGI'kiIIGtiC Disorders
`
`2:3:
`A537
`
`Friday, April 30, 2004
`66. Neural Repair and Rehabilitation
`67. Glionlas: Clinical Studies
`68. Neuro-Oncology: Basic Science Studies
`
`Key to Abstracts
`.
`,
`.
`Scientlfic PrOgram §chommlttee Members
`and AbStraCt ReVlewerS
`Meeting Program Overview
`2004 P]
`.
`enar Ses i
`'
`.
`_
`.
`S 0115
`y
`Selentlfic Award Presentations
`Meeting Exhibitors
`.
`Poster Presentation Floor Plan
`_
`‘
`SCIencc Gommlttee
`Key to Indexes
`-
`,
`SubJect Index
`_
`_
`Index Of Part1c1pants
`Index to Advertisers
`
`A540
`A542
`A545
`
`B16
`
`B32
`B34
`B44
`
`B55
`565
`B84
`A1
`A547
`A548
`A592
`A626
`
`B6 NEUROLOGY 62 April 2004 (Suppl 5)
`
`IPR2015—00410
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`Petitioners' EX. 1018
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`Page 3
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`IPR2015-00410
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`Page 3
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`

`

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`
`iiiii
`
`o
`‘Jwasauaaln;
`
`u EI
`
`>'
`
`- Nc
`
`This material may be protected by Copyright law (Title 17 US. Code)
`
`effective as CBZ and VPA. However, TPM 100 was better toler-
`ated than TPM 200, CBZ or VPA. Discontinuations due to adverse
`events: TPM 100, 19%; TPM 200, 28%; CBZ, 25%, and VPA, 23%.
`CONCLUSIONS: Taken together, these studies demonstrate
`that 100 mg/day TPM ,is an effective dose, is at least as effective
`as CBZ and VPA, but is better tolerated. 100 mg/day TPM can
`therefore be recommended as the initial target dose for previously
`untreated patients with epilepsy.
`Supported by: Johnson & Johnson Pharmaceutical Research &
`Development, L.L.C.
`Disclosure: Dr. Ben-Menachem has received research grants
`from Johnson & Johnson Pharmaceutical Research & Development,
`L.L.C, UCB Pharma, GlaxoSmithKline and Cyberonics; consulting
`fees from Johnson & Johnson Pharmaceutical Research & Develop—
`ment, L.L.C, GlaxoSmithKline, UCB Pharma and Cyberonics; and
`honoraria from Janssen—Cilag, Ortho-McNeil Pharmaceutical, UCB
`Pharma, Cyberonics and GlaXOSmithKline. Dr. Privitera has re—
`ceived consulting fees from GlaxoSmithKline, Novartis, Ortho-
`McNeil/Johnson & Johnson, Pfizer/Parke—Davis, UCB and Shire,
`and honoraria for speaking from GlaxoSmithKline, Ortho—McNeil/
`Johnson & Johnson, Pfizer/Parke—Davis, UCB and Shire. Dr.
`Squires, Dr. Wang, and Dr. Twyman are employees of Johnson &
`Johnson Pharmaceutical Research & Development, L.L.C.
`
`P041 04
`Lamotrigine Serum Concentration during
`Taper of Phenytoin: Time Course of
`Deinduction
`Mary Ann Werz, Cleveland, OH, Barbara E. Swartz, Newport
`Beach, CA
`
`OBJECTIVE: This study investigated the time course and
`dose-dependence of phenytoin taper on lamotrigine serum concen—
`tration.
`BACKGROUND: Phenytoin (PITT) is a powerful inducer of
`lamotrigine (LTG) metabolism. Therefore, it may be difficult to
`achieve adequate LTG serum concentrations during adjunctive
`treatment with PHT. Furthermore, a transient exacerbation of
`seizures may occur during conversion to monotherapy dependent
`upon the time course of deinduction of LTG glucuronidation en-
`zymes. Analysis of data from the published active control, conver-
`sion to monotherapy trial
`suggested that LTG serum
`concentrations doubled following withdrawal of PHT. Further-
`more, LTG serum concentrations did not increase until PHT was
`completely stopped. Interpretation of this study is potentially lim-
`ited by the rapid withdrawal of PHT in weekly decrements of
`20%, as a week may be insufficient for deinduction of hepatic
`enzymes to reach steady-state.
`DESIGN/NIETHODS: Patients treated with PHT with either
`incomplete control or unacceptable side effects were recruited for
`conversion to LTG monotherapy. Seven patients have thus far
`completed. Lamotrig‘ine was titrated to 400 to 500 mg total daily
`dose over three months. PHT was then withdrawn every three
`weeks in decrements of one—third the initial dose. Serum concen-
`trations were measured weekly for ten weeks. Blood draws oc-
`curred on the same day of the week and at the same time of day.
`PHT dose reductions were scheduled to occur immediately after a
`blood draw. Patients did not alter other medications during the
`protocol, PHT was measured at our institution using the CEDIA
`Phenytoin II (ROCHE) immunoassay. LTG was measured at
`ARUP Laboratories by HPLC.
`RESULTS: Five patients were recruited who had adverse
`events to the prior medication and two had had incomplete sei—
`zure control. Seven of seven patients have thus far been success-
`fully
`converted
`to LTG monotherapy. Baseline
`serum
`concentrations of LTG ranged from 3.6 to 4.5 meg/ml, attained on
`400 mg total daily dose, with PHT serum concentrations ranging
`fi‘OIn 8. 7 to 27.0 meg/ml. Decrease in PHT doses up to 67 %
`increased LTG serum concentrations by less than 10%; At that
`time PHT serum concentrations averaged 2.4 mcg/ml(ra1ige 2. 2 to
`2 7mcg/ml). One, two, and three weeks after PHT cessation, the
`ave1age LTG serum concentration had increased 4.7, 82, and
`109%,grespectively. The range of maximal increase was 50—230%.
`CONCLUSIONS: LTG serum concentrations typically double
`with withdrawal of PHT. The increase does not occur until PHT
`
`concentrations are under 2.5 meg/ml. The increase then occurs
`quite quickly with half in the first week of complete PHT with~
`drawal. Complete deinduction of glucuronidation appears to re-
`quire two to three weeks though our current small sample size
`limits complete accuracy of the time course. Epilepsy patients
`may require special efforts at seizure prophylaxis during taper
`from PHT and for several weeks thereafter.
`Supported by: Investigator Initiated award from Glaxo—Smith-
`Kline
`Disclosure: Dr, Werz and Dr. Swartz have nothing to disclose.
`
`
`
`Aging and Dementia: Treatment
`
`PO4.105
`Efficacy of Once-Daily Galantamine .
`Extended-Release in Patients with Mild to
`Moderate Alzheimer’s Disease
`
`Henry Brodaty, New South Wales, Australia, Bing Yan, Chan-
`drasekharRao V. Damaraju, Titusville, NJ
`
`OBJECTIVE: To assess the efficacy ofonce-daily galantamine
`in patients with mild to moderate Alzheimer’s disease (AD).
`BACKGROUND: Galantamine is an acetylcholinesterase in»
`hibitor and allosteric modulator of nicotinic cholinergic receptors.
`Clinical trials have shown that 16 or 24 nag/day of an immediate-
`release (IR) formulation (b.i.d.) improves cognition and global per—
`formance compared with placebo, maintains activities of daily
`living, and delays the emergence of neuropsychiatric symptoms. A
`once-daily extended-release (ER) formulation of galentamine was
`developed to enhance ease of use and potentially facilitate compli-
`ance.
`
`‘DESIGN/METHODS: The efficacy of galantamine ER was
`evaluated in a 6—month, double-blind, flexible-dose, multicenter
`trial of 971 patients with mild to moderate AD (Mini-Mental State
`Examination [MMSE]
`score 10-24; AD Assessment Scale-
`cognitive subscale [ADAS-cog] score 218). Patients were random—
`ized to receive galantamine ER (n=320), galantamine IR (n=32’7),
`or placebo (n=324) with total daily dosages escalating by 8 mg/
`day every 4 weeks to a maximum of 16 or 24 mg/day. Primary
`efficacy outcomes were change from baseline in ADAS-cog/ll
`scores and Clinician’s Interview-Based Impression of Change-Plus
`Caregiver Input (CIBIC-plus) score at Week 26. Key secondary
`outcomes included changes from baseline in AD Cooperative
`Study-Activities of Daily Living (ADCS-ADL) score at Week 26.
`RESULTS: Mean ADAS-cog/ll scores were significantly im-
`proved from baseline at Week 26 in galantamine ER and IR
`groups compared with placebo (-1.4, -1.8, and 1.3, respectively;
`P<0.001). No significant differences in treatment response were
`observed between the galantamine groups. The galantamine ER
`group also maintained daily functioning (ADCS-ADL scores) sig-
`nificantly better than the placebo group (P=0.003), consistent
`with previously reported results for galantamine IR. Both galan-
`tamine groups improved or maintained global functioning (CIBIC-
`plus scores) numerically better than the placebo group at Week
`26; the difference approached statistical significance for the ER
`group (P=0.086). There was, however, an overrepresentation of
`subjects enrolled with mild AD (MMSE scores >22) in the placebo
`group, contributing to a disproportionately high placebo response
`rate in CIBIC-plus scores (77%). Galantamine ER was safe and
`well tolerated. The most frequently reported adverse events in the
`galantamine ER group were similar to those reported for galan-
`tamine IR, with fewer nausea and vomiting episodes during dose
`escalation in the galantamine ER group.
`CONCLUSIONS: Galantamine ER provides treatment effi-
`cacy similar to galantamine IR for mild to moderate AD while
`offering the convenience of once~daily dosing and better tolerabil-
`ity during dose escalation.
`Supported by: Janssen Pharmaceutica Products, L.P., Titus-
`ville, New Jersey.
`Disclosure: Dr. Brodaty is a consultant for Janssen Pharma-
`ceutica and has received honoraria from Janssen Pharmaceutica
`
`A317 NEUROLOGY 62 April 2004 (Suppl 5)
`
`IPR2015—00410
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`

`for speaking. Dr. Yan and Dr. Damaraju are employees of John~
`son & Johnson Pharmaceutical Research & Development LLC.
`
`P045106
`
`Postmenopausal Hormone Therapy and Risk
`of Cognitive Decline
`Francine Grodstein, Boston, MA
`
`OBJECTIVE: To examine the relation of postmenopausal hor-
`mone use to cognitive decline.
`BACKGROUND: A large randomized trial of postmenopausal
`women over aged 65 years reported an increased risk of cognitive
`decline with combined estrogen and progestin treatment. How-
`ever, questions remain, including the effect of estrogen alone, or of
`hormone therapy initiated at menopause versus many years after
`menopause.
`DESIGN/METHODS: The Nurses Health StudyIs an ongo—
`ing, prospective cohort begunin 1976, comprising 121,700 nurses.
`Women continuously provide updated and detailed health infor-
`mation via biennial mailed questionnaires. This sub~study in-
`cludes 13,807 participants who completed two telephone cognitive
`assessments, 2 years apart, between 1995—2002 when they
`ranged in age from 70—81 years. We tested general cognition,
`verbal memory, category fluency, and attention. Participation and
`follow-up are over 90%.
`We used logistic regression to estimate multivariate-adjusted
`risks of substantial decline in cognitive function and linear re-
`gression to examine 1nultivariate~adjusted mean decline, across
`hormone groups. Extensive data on potential confounding vari-
`ables was considered including: age, education, diabetes, high
`blood pressure, vitamin supplements, age at menopause, body
`mass index, smoking, physical activity, depression, alcohol intake
`and NSAID use.
`RESULTS: Overall, after multivariate adjustment, we found
`little difference in the rates of cognitive decline between current
`hormone users and never users. However, for long~term users of
`estrogen alone or combined with progestin, there were sugges—
`tions of increased risk of substantial decline on most cognitive
`tests (relative risks=1.25—1.72).
`Rates of cognitive decline were similar between women initiat—
`ing hormone use at menopause and women who never used hor-
`mone therapy. Although only 4% of hormone users initiated
`hormone therapy after age 65 years, the greatest decline was
`observed among these women: for those who began taking hor—
`mones at age 65 years or older, the relative risk of substantial
`decline in general cognition was 1.74 (95% CI 1.08,2.81) compared to
`never users, and mean difference in decline for these late initiators
`compared to never users was -0.43 points (95% CI —O.73, —0.12).
`CONCLUSIONS: In this large cohort study, postmenopausal
`hormone therapy provided no cognitive benefits in older. women.
`There may be risks in certain subgroups
`Supported by: Grants from NIH and Ellison Medical Founda-
`tion
`Disclosure: Dr. Grodstein received fees as a temporary consul-
`tant from Schering—Plough and received honoraiium for lectures
`from Novo Nordisk, Schering Plough, WyethAyerst, Pfizer, and
`Orion Pharma.
`
`PO4.107
`Functional and Behavioral Effects of
`Memantine in Alzheimer’s Disease
`
`Jeffrey Cummings, Los Angeles, CA, Christopher van Dyck, New
`Haven, CT, Frederick Schmitt, Lexington, KY, Stephen M. Gra-
`ham, Jason T. Olin, James Jin, Jersey City, NJ, Pierre N. Tariot,
`Rochester, NY
`
`OBJECTIVE: The objective was to assess the effect of me-
`mantine on functional and behavioral domains in moderate to
`severe Alzheimer’s disease (AD) patients stabilized on donepezil.
`BACKGROUND: AD is a progressive, neurodegenerative ill-
`ness associated not only with cognitive deficits but also with func-
`tional decline and behavioral disturbances. Memantine is a low-
`
`moderate affinity, uncompetitive NMDA receptor antagonist that
`is thought to allow normal physiological activation while blocking
`prolonged pathological activation of the NMDA receptor, one fac-
`tor implicated in the pathology of AD. Memantine was approved
`for the treatment of moderate to severe AD based on demon-
`strated efficacy in cognition, function and global status in two
`trials (the of which included patients treated with ongoing done-
`pezil th’erapy. This report p1ovides further analyses of the func-
`tional and behavioral effects of memantinein moderate to seve1e
`AD patients stabilized on donepezil in this latter study.
`DESIGN/METHODS: A 24-week double~blind, placebo-
`controlled trial was conducted in moderate to severe AD patients
`on a stable donepezil regimen (N=395, ITT population) and ran-
`domized to memantine or placebo. Functional abilities were as-
`sessed using the modified ADCS-ADL19 scale and the BGP Care
`Dependency subscale. ADCS—ADL19 was given at baseline, weeks
`4-, 8, 12, 18 and the final visit (Week 24), while the BGP Care
`Dependency was administered at baseline and at the final visit.
`Behavioral symptoms were assessed using the Neuropsychiatric
`Inventory (NPI), and data were analyzed at baseline, Week 12
`and the final visit. The efficacy analyses were based on the ITT
`population, using both 00 and LOCF approaches.
`RESULTS: Memantine-treated patients demonstrated signifi~
`cantly higher functional ability (ADCS—ADLl9 or BGP Care De-
`pendency) compared to placebo-treated patients (p=0.028, p=0.001,
`respectively). A by—item analysis of ADCS-ADL19 revealed that at
`endpoint, abilities in grooming, being left alone, and watching televi-
`sion were statistically significant, in favor of memantine. NPI total
`score favored memantine treatment over placebo (p=0.0002). NPI
`domains demonstrating statistically significant improvement af-
`ter 24 weeks in memantine—treated patients were agitation/
`aggression, irritability/lability, and appetite/eating,
`CONCLUSIONS: Memantine treatment in combination with
`ongoing donepezil therapy is associated with less functional and
`behavioral deterioration in Alzheimer’s disease than with donepe-
`zil therapy alone.
`Supported by: Forest Laboratories, Inc.
`Disclosure: Dr. Cummings received consulting fees from Forest
`Laboratories, Inc. Dr. van Dyck received research support from
`Forest Laboratories, Inc. Dr. Schmitt received research support
`from Forest Laboratories, Inc. Dr. Graham is an employee of
`Forest Research Institute. Dr. Olin is an employee of Forest Re-
`search Institute. Dr. Jim is an employee of Forest Research Insti—
`tute. Dr. Tariot
`received research support
`from Forest
`Laboratories, Inc., received consulting fees from Forest Laborato-
`ries, Inc. and received honoraria for speaking from Forest Labora—
`tories, Inc.
`
`PO4.108
`
`Incidence of Presumptive Tardive
`Dyskinesia in Elderly Patients Treated with
`Olanzapine or Conventional Antipsychotics
`
`Bruce J. Kinon, Virginia Stauffer, Christopher Kaiser, Sara
`Kollack—Waiker, Waller Debcrdt, Indianapolis, IN
`
`OBJECTIVE: To determine the risk of developing dyskinetic
`symptoms in elderly patients treated with olanzapine versus con—
`ventional antipsychotics.
`BACKGROUND: Incidence rates of presumptive tardive (lys-
`kinesia (TD) were compared in acutely psychotic or agitated el-
`derly patients treated with olanzapine (OLZ) or conventional
`antipsychotic (CNV) drug therapy.
`DESIGN/METHODS: Patients without TD were randomized
`to OLZ (2.5—20 mg/day; n=150) or CNV (dosed per label; n=143)
`therapy, and underwent a 6~week drug tapering/drug initiation
`period, followed by reassessment of TD. Patients remaining with-
`out TD after six weeks were treated with OT7 or CNV ['or up to 1
`year. Primary analysis was time-to-TD incidence, defined as rat"
`ing on the Abnormal Involuntary Movement Scale (AIMS) 0f 91‘
`the1: A) moderate severity (>3)1n 1 body region or mild severity
`(>2)1n 2 or more body regions, or B) moderatesseverity (>3) 1n 1
`body region.
`RESULTS: Patientsin CNV group were at a greater risk for
`presumptive TD than patients in OLZ group (criteria A 01' B
`p< 05). Incidence of presumptive TD that persisted for at least 1
`
`A318 NEUROLOGY 62 Apri12004 (Suppl 5)
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`as_l
`Ea
`inn-
`1,4
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`'3
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`IPR2015—00410
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`Petitioners' Ex. 1018
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`Page 5
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`IPR2015-00410
`Petitioners' Ex. 1018
`Page 5
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