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`: Abstracts from the
`: XXII CINPCongress,
`Montréal, June 23-27, 2002
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`; The Official Scientific Journal of the
`: CollegiumInternationale
`? Neuro-psychopharmacologicum
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`Supplied bytheBritishLibrary-"Theworld'ss knowledgesecHONEblkBIT 2005
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`Page 1 of 3
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`ALKERMESv. OTSUKA
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`IPR2017-00287
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`OTSUKA EXHIBIT 2005
`ALKERMES v. OTSUKA
`IPR2017-00287
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`

`

`
`
`The International Journal of
`Neuropsychopharmacology
`
`Official Scientific Journal of the
`Collegium Internationale Neuro-psychopharmacologicum (CINP)
`
`
`Volume 5
`© Supplement1
`°
`June 2002
`
`Abstracts from the XXIII CINP Congress,
`Montréal June 23-27, 2002
`
` Sey UNIVERSITY PRESS
`
`Page 2 of 3
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`

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`_ dose reduciion was allowed to aripiprazole 20 mg and haloperidol 7 mg. Efficacy
`evaluations inctuded PANSS and MADRSscores.
`Results: A significantly greater proportion ofpatients treated with anpiprazote
`demonstrated response and remained on treatment at weeks 8, 26, and 52 com-
`pared to haloperidol (Week 52: 40% vs 27%, p<0.001). Anpiprazole produced
`statistically significant
`improvements in the PANSS Negative Subscale Score
`at weeks 26 and 52 (both p<0.03). Aripiprazole also demonstrated significant
`improvementfrom baseline in depressive symptoms as shown in the MADRS at
`weeks 8, 26, and 52, compared to haloperido! (all p<0.03). The discontinuation
`rate due to an adverse event was significantly lower in the aripiprazole group
`than in the haloperidol group (p<0.004). The overall incidence of EPS-related
`adverse events was significantly lower with aripiprazole than with haloperidol
`(p< 0.001). Both treatments resulted in comparable weight gain. There was no
`significant difference in QT, interval between both groups.
`Conclusion: Aripiprazole may represent
`the next-generation antipsychotic
`leading to increased compliance in schizophrenia due to significantly greater
`improvements in negative and depressive symptoms, and a superior safety and
`tolerability profile compared to haloperidol.
`
`P.4.E.033] ARIPIPRAZOLE VS. PLACEBO IN THE TREATMENT
`OF CHRONIC SCHIZOPHRENIA
`
`
`WH. Carson!, T.A. Pigott?, A.R. Saha’, M.W. Ali?, R.D. McQuade*, AF.
`Torbeyns’, E.G. Stock!. ! Bristol-Myers Squibb, Wallingford, CT; ? University of
`Florida, Gainesville, FL; 4 Otsuka Maryland Research Institute, LLC, Rochville,
`MD; ‘Bristol Myers Squibb, Lawrenceville, NJ, USA; 4 Bristol-Myers Squibb,
`Waterloo, Belgium
`
`Objective: To assess relapse prevention with aripiprazole compared to placebo
`over 26 weeks in patients with chronic but stable schizophrenia.
`Methods: A multicenter, randomized, double-blind, placebo-controjled study
`was conducted in 310 patients with chronic schizophrenia considered stable (no
`significant improvement or worsening in last 3 months and baseline PANSS=82)
`randomized to aripiprazole 15 mg/day or placebo. Efficacy measures included
`time-to-relapse, number ofrelapses and PANSStotal score.
`.
`Results: Compared to placebo, treatment with aripiprazole was shown to be
`effective in increasing time-to-relapse, and resulted in significantly fewer patients
`relapsing at endpoint versus placebo (34% vs. 57%, respectively). Aripiprazole
`produced significantly greater improvement in PANSStotal score and PANSS
`positive subscale score, compared to placebo. Patients on aripiprazole showed
`continuing stability on the PANSS negative subscale score. Aripiprazole was
`generally well tolerated with an adverse eventprofile comparable to placebo. No
`clinically significant changes occurred in SAS, AIMS, and Bames Akathisia
`scores in cither group. There were no elevations in plasma prolactin levels
`with aripiprazole compared to placebo. No clinically important cardiac risks
`were associated with aripiprazole. Weight gain associated with aripiprazole was
`comparable to placebo.
`Conclusion: Aripiprazole was demonstrated to delay the rate of and time to
`relapse in patients with chronic schizophrenia, doing so with a favorable safety
`and tolerability profile. Aripiprazole, therefore, represents an important addition
`to the current antipsychotic armamentarium.
`
`P,4.E.034| swiTCHING TO ARIPIPRAZOLE MONOTHERAPY
`
`D. Casey’, A.R. Saha”, M.W. Ali2, D.N. Jody?, M.J. Kujawa‘, E.G. Stock’, G.G.
`Ingenito’. ‘Mental Illness Research, Education and Clinical Center, Portland,
`VA; ? Otsuka Maryland Research Institute, LLC, Rockville, MD; 4 Bristol-Myers
`Squibb, Lawrenceville, NJ; ‘Bristol-Myers Squibb, Plainsboro, NJ;
`5 Bristol-
`Myers Squibb, Wallingford. CT. USA
`
`Objectives: To assess the safety and tolerability of switching patients from
`current antipsychotic therapy to aripiprazole, a newly developed antipsychotic,
`with a unique mechanism of action (dopamine-serotonin system stabilizer). The
`impact onefficacy was also evaluated.
`Methods: This multicenter, randomized, 8-week, open-label Phase [I study
`involved 311 patients with chronic, stable schizophrenia or schizoaffective dis-
`order who had received monotherapy with a typical (haloperidol or thioridazine)
`or atypical (risperidone or olanzapine) antipsychotic for 21 month. Patients
`were randomized into 3 groups: Group 1 — Immediate initiation of 30 mg/day
`aripiprazole with simultaneous abrupt discontinuation of current antipsychotic
`(n=104), Group 2 — Immediate initiation of 30 mg/day aripiprazole while
`tapering off current antipsychotic over 2 weeks (n=104), Group 3 — Titration
`of aripiprazole over 2 weeks (from 10 mg/day to 30 mp/day) while tapering off
`current antipsychotic (n=1!03).
`
`P4.E. Antipsychotics and schizophrenia — 4
`
`$187
`
`Results: Safety and tolerability results were similar across treatment groups.
`There were no differences in discontinuations due to adverse events across the
`three groups. Antipsychotic efficacy was maintained in all groups throughout the
`study and improvement was seen from baseline in PANSS-total, -negative, and
`-positive subscales, and CGI-Improvement Score.
`Conclusions: Switching to aripiprazole is safe and well-tolerated and can be
`initiated at an efficacious dose without having to gradually increase the dose of
`aripiprazole.
`
`P.4.E.035] PBARMACOKINETICS AND SAFETY OF
`ARIPIPRAZOLE AND CONCOMITANT MOOD
`STABILIZERS
`
`
`L. Citrome’, R. Josiassen?, N. Bark’, K-S. Brown‘, S. Mallikaarjun’, D.E.
`Salazar’.
`'Nathan-S. Kline Institute; ?Arthur P Noyes Research Foundation,
`Norristown, PA; ? Bronx Psychiatric Center, Bronx, NY: ‘Bristol-Myers Squibb,
`Wallingford, CT: ’ Otsuka Maryland Research Institute, LLC, Rockville, MD, USA
`
`Objective: To assess the pharmacokinetic and safety profile of aripiprazole,
`an antipsychotic with a unique pharmacologic profile of dopamine D2 partial
`agonism, serotonin SHT), partial agonism, and SHT24 antagonism, when coad-
`ministered with lithium or divalproex sodium.
`Methods: Two open-label, sequential treatment design studies were conducted
`in chronically institutionalized patients with schizophrenia or schizoaffective
`disorder requiring treatment with lithium (n=7) or divalproex sodium (n=6).
`Patients received aripiprazole 30 mg/day on Days 1-14 and aripiprazole with
`concomitant therapy on Days 15-36. Lithium was titrated from 900 mg until
`serum concentrations reached 1.0-1.4 mEq/L for 25 days. Divalproex sodium
`was titrated to 50-125 mg/L.
`Resuits: Coadministration with lithium increased mean Cys, and AUC values
`of aripiprazole by about 19% and 15%, respectively, while the apparent oral
`clearance decreased by 15%. There was no effect on the steady state phar-
`macokinetics of the active metabolite of aripiprazole. Coadministration with
`divalproex sodium decreased the AUC, Coax, and Cmin of aripiprazole by 24%,
`26%, and 22%, respectively, with minimal effects on the active metabolite.
`Spontaneous adverse events reported with coadministration of aripiprazole and
`therapeutic doses of lithium or divalproex sodium were consistent with those
`observed with monotherapy of aripiprazole. There were no clinically. relevant
`electroencephalographic changes.
`Conclusion: Aripiprazole can be administered safely with therapeutic doses
`oflithium or divalproex sodium in patients with schizophrenia or schizoaffective
`disorder.
`
`P.4.E.036] LOPERIDONE ADMINISTERED TWICE-DAILY OR
`ONCE-DAILY IS WELL TOLERATED: A PROSPECTIVE
`DOUBLE-BLIND, RANDOMIZED, PARALLEL-GROUP,
`STUDY
`°-
`
`M. Schmidt, T. Maktovits-Gupta, Z. Lin, A. Guven. Novartis Pharmaceuticals
`Corp, East Hanover, USA
`
`Objective: To compare thesafety, tolerability and efficacy of bid and qd dosing
`regimens of iloperidone with haloperidol in patients with chronic schizophrenia.
`Method: Patients (n=120) were randomized in a 2:2:] ratio to receive bid
`iloperidone (12mg/d), employing either alternate day ordaily titration schedules,
`or bid haloperidol (15mg/d). Patients were maintained on these doses until Day
`28, after which the iloperidone patients were re-randomized to receive either
`iloperidone 4 mg bid or 8 mg qd from Days 29 to 42. The dosage could be
`increased to 12 mg/d after Day 35 if required. The PANSS was usedto assess
`efficacy.
`Results: Both bid and gd dosing regimens were gencrally well tolerated and
`the dropoutrate due to AE's was similar in all groups (6-9%). Hoperidone was
`not associated with an increase in EPS, and concomitant use of benztropine was
`low in both bid and qd groups (4% each, compared with 64% in the haloperidol
`group). Efficacy achieved during thefirst four weeksof treatment was maintained
`at Day 42 in both dosing groups. There were no significant differences between
`groups on the PANSSat any timepoint.
`Conclusions: Both qd and bid dosing ofiloperidone were safe and well toler-
`ated. The incidence of EPS was low with iloperidone compared to haloperidol.
`There was no loss ofefficacy in switching from bid to qd dosing of iloperidone.
`
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