2002 ANNUAL MEETING
`
` AMERICAN PSYCHIATRIC ASSOCIATION
`
`
`
`Philadelphia, PA @ May 18-23, 2002
`
`1 of 2
`
`Alkermes, Ex. 1007
`
`1 of 2
`
`Alkermes, Ex. 1007
`
`

`

`haloperidol, IM ziprasidone was consistently associated with a
`lower movement disorder burden (eg, akathisia, dystonia, EPS,
`hypertonia)atall doses investigated.In all studies,clinically signifi-
`cant changesin blood pressure and heart rate associated with
`IM ziprasidone were isolated and transient; treatment-emergent
`postural hypotension was observed in one ziprasidone-treated
`patient in one study. There were no QTc values >500 msecwith
`IM ziprasidone.
`Conclusion:In clinical trials, IM ziprasidone in divided doses up
`to 80 mg/day was well tolerated, with low incidences of AE-related
`discontinuations and movement disorder AEs.
`
`Results: Aripiprazole producedstatistically significant improve-
`ments in Y-MRSTotal score (-8.15 vs. —3.35, p<0.01) compared
`to placebo. The responserate wassignificantly higherin the aripi-
`prazole group than the placebo group (40%vs. 19%, p<0.01). For
`all efficacy variables, aripiprazole separated from placebo by day
`4. Discontinuations due to adverse events did not differ between
`the aripiprazole and placebo groups, and there were nosignificant
`changesin weight versus placebo.
`Conclusion: Aripiprazole was effective and well tolerated in the
`treatment of acute mania in patients with bipolar disorderin this
`randomized, placebo-controlledtrial.
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`NR313
`Olanzapine Improves Tardive Dyskinesia in Patients
`with Schizophrenia
`Bruce J. Kinon, M.D., Lilly Research Lab, Eli Lilly And
`Company,Lilly Corporate Center, Indianapolis, IN 46285,
`Virginia L. Stauffer, Pharm.D., Lynn Wang, M.S., Khanhn T. Thi
`Summary:
`Objective: We report preliminary findings of the effects of olan-
`zapine (OLZ) treatment upon tardive dyskinesia TD.
`Methods: Eligible schizophrenic subjects met restricted Re-
`search Diagnosis Tardive Dyskinesia criteria (restricted RD-TD)
`that specified for abnormal involuntary movements to be of at
`least moderate severity. Subjects received OLZ, 5-20 mg/day
`for 8 months within a double-blind design that included up to 2
`medication reduction (75%) periods of 2 weeks duration. TD was
`assessed with the Abnormal Involuntary Movement Scale (AIMS)
`and psychopathology with the Positive and Negative Syndrome
`Scale (PANSS).
`Results: A significant reduction in mean AIMS Total score was
`demonstrated (N=95; BL=11.9; EP=7.5; p<.001; LOCF). Nearly
`70%of subjects no longer met the restricted RD-TDcriteria after
`up to 8 monthsof treatment, with greater than 50% improving as
`early as 8 weeks. Nostatistically significant rebound worsening
`of TD was found during the blinded drug reduction periods. A
`significant improvement in the PANSS occurred (BL=68.2; EP=
`59.7; p<.001, LOCF).
`Conclusion: These data, suggesting an ameliorative, rather than
`masking effect, and the concurrent further improvementin clinical
`status suggests that OLZ mayoffer a potential treatment alterna-
`tive for managing the schizophrenic patient with pre-existing TD.
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`NR314
`Aripiprazole Versus Placebo in Acute Mania
`Paul E. Keck, Jr., M.D., Biological Psychiatry Department, Univ.
`of Cincinnatti College of Medicine, 231 Albert Sabin Way,
`ML559, Cincinnati, OH 45267-0559, Anutosh R. Saha, Ph.D.,
`Taro Iwamoto, Ph.D., Darlene Jody, M.D., Stavros
`Tourkodimitris, Ph.D., Donald G. Archibald, M.Phil., Ronald N.
`Marcus, M.D.
`
`Summary:
`Objective: To compare the efficacy and safety of aripiprazole,
`the first next-generation atypical antipsychotic with a unique mech-
`anism of action (dopamine-serotonin system stabilizer) to placebo
`in patients with acute bipolar mania.
`Methods: This PhaseIll, multicenter, double-blind, placebo-
`controlled study randomized 262 patients with acute mania to
`aripiprazole 30 mg (reduced to 15 mg if unable to tolerate) or
`placebo for 3 weeks. Patients remained hospitalized for a mini-
`mum of two weeksof the treatment phase. The primary measure
`of efficacy was the change in Y-MRS Total score. Response was
`defined as a decrease of >50%in Y-MRS Total score.
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`NR315
`Ziprasidone Versus Olanzapine in Schizophrenia:
`Six-Month Continuation Study
`George M. Simpson, M.D., Department of Psychiatry, LAC/
`USMC Medical Center, 2020 Zonal Avenue, IRD Room 20, Los
`Angeles, CA 90033; Peter J. Weiden, M.D., Teresa A. Pigott,
`M.D., Steven J. Romano, M.D., Cynthia Siu, Ph.D.
`Summary:
`Objective: To compare long-term efficacy and tolerability of zi-
`prasidone and olanzapine in schizophrenia or schizoaffective dis-
`order.
`Methods: This 6-month, blinded continuation study followed
`hospitalized patients who had completed a 6-week randomized
`trial with satisfactory clinical response (CGI-| <2 or >20%reduction
`in symptom severity by PANSS Total) and were discharged on
`olanzapine 5-15 mg QD (n=71) or ziprasidone 40-80 mg BID (n=
`62). Primary efficacy measures were BPRS and CGI-S; secondary
`variables included PANSSTotal and Positive and Negative Sub-
`scale scores. Tolerability assessments includedfastinglipids, in-
`sulin, glucose, and weight.
`Results: Ziprasidone- and olanzapine-treated patients demon-
`strated comparable changes in BPRS, CGI-S, and PANSSTotal
`and Subscale scores from baseline of 6-week study to endpoint
`of 6-month continuation. Changes during continuation phase did
`not differ significantly between groups. Olanzapine-treated pa-
`tients exhibited significant mean increases versus ziprasidonein
`endpoint weight (P<0.001) and BMI (P=0.001), and significant
`median increases versus baseline in LDL-C (P<0.01),
`insulin
`(P<0.05), glucose (P=0.05), and fasting liver enzymes (P<0.05).
`Both agents displayed low incidence of movementdisorders. No
`patients had QTc 2500 msec.
`Conclusions: Ziprasidone and olanzapine demonstrated com-
`parable antipsychotic efficacy in long-term treatment. Olanzapine
`patients alone exhibited sustained weight gain and deleterious
`metabolic changes.
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`NR316
`Antipsychotic Monotherapy Versus Combination
`Treatment with Valporate in Hospitalized Patients
`with Acute Schizophrenia: A Double-Blind, Multi-
`Center Study
`Leslie L. Citrome, M.D., Clinical Research/CREF, Nathan Kline
`Institute, 140 Old Orangeburg Road, Building 37, Orangeburg,
`NY 10962-2210, David G. Daniel, M.D., Adel A. Wassef, M.D.,
`Katherine A. Tracy, M.D., Patricia Wozniak, Ph.D., Daniel E.
`Casey, M.D.
`Summary:
`Objective: This study comparedthe efficacy and safety of atypi-
`cal antipsychotic monotherapy (olanzapine or risperidone) versus
`combination treatment with valproate (divalproex sodium) in pa-
`tients with an acute episode of schizophrenia.
`
`86
`
`2 of 2
`
`Alkermes, Ex. 1007
`
`2 of 2
`
`Alkermes, Ex. 1007
`
`