`
`Schizoph renia Resea reh
`1'».I"I:Iu|ume '33. Supplement, February 2003. Pages lfiS—lfilfi
`
`
`
`322 — Efficacy/tolerability ofpaliperidone
`palmitate: 9-week, placebo-controlled study in
`
`schizophrenia patients
`
`M. Kramer 1, R. Litman ‘1,R. Lane 3, M. Kujawa1,P. Lim 1, D. Hougln 1, M. Eerdekens 4
`
`Mylan V. Janssen (IPR2020-00440) EX. 1039, p. 001
`
`Mylan v. Janssen (IPR2020-00440) Ex. 1039, p. 001
`
`

`

`ABSTRACTS / Schizophrenia Research 98 (2008) 3–199
`
`165
`
`320 – IMPROVEMENTS IN EVERYDAY FUNCTIONING WITH
`ATYPICAL ANTIPSYCHOTIC TREATMENT: A RANDOMIZED
`LONG-TERM COMPARISON OF ZIPRASIDONE AND
`HALOPERIDOL
`
`P. Harvey 2, C. Kremer 1, I. Lombardo 1.
`
`1Pfizer Inc., 235 East 42nd Street, New York, NY 10017 USA
`2Department of Psychiatry and Behavioral Sciences, Emory University
`School of Medicine, Woodruff Memorial Building, 101 Woodruff
`Circle, Suite 4000, Atlanta, GA 30032 USA
`
`Presenting Author details: charlotte.m.kremer@pfizer.com
`235 East 42nd St, NY 10016 New York, United States,
`Tel.: +1 212 733 0140; fax: +1 646 441 4614.
`
`Background: Several studies have examined the development of
`clinical remission during treatment of schizophrenia. However, devel-
`opment of remission may not be associated with functional recovery,
`which must be examined separately. This study examined the
`development of “functional remission” in a long-term double-blind
`comparison of haloperidol and ziprasidone.
`Methods: Community dwelling patients with schizophrenia were
`randomized to treatment with haloperidol (n = 47) or ziprasidone dosed
`either once or twice daily (n = 139) and re-examined at follow-up
`intervals ranging up to 196 weeks. Their community functioning was
`examined with the Heinrichs–Carpenter Quality of Life Scale. Both
`total scores for employment and social functioning and achievement of
`improvement milestones across the individual items were analyzed.
`Results: Mixed random effects models adjusting for length of follow-
`(p b .05)
`up indicated a significant
`treatment effect
`favoring
`ziprasidone for social functioning. While the mixed model was not
`significant for employment, the 95% confidence interval for changes
`scores in the haloperidol group overlapped with 0, while mean change
`was significantly greater than 0 for the ziprasidone group. Most
`importantly,
`the distributions of change scores across the items
`showed significantly more items where endpoint scores were 5 or 6
`(minimal to no impairment) in ziprasidone treated patients, (X2[8]
`= 16.92, p = .03). There was an overall shift in the distribution of
`endpoint scores, with haloperidol patients having fewer items where
`substantial change was detected than ziprasidone patients.
`Conclusions: Treatment with ziprasidone was associated with greater
`functional gains than treatment with haloperidol, even when
`differential dropout was controlled. Both treatment retention and
`functional gains favored ziprasidone in this long-term study.
`
`doi:10.1016/j.schres.2007.12.387
`
`321 – COMPARISON OF POST-MARKETING SPONTANEOUSLY
`REPORTED ADVERSE EVENTS IN OLANZAPINE-TREATED
`ADOLESCENT AND ADULT PATIENTS
`
`L. Kryzhanovskaya1, D. Falk 1, L.M. Schuh 1, J. Wernicke 1.
`
`1Lilly Research Laboratories, Indianapolis, USA
`
`Presenting Author details: zyp_sci_comm@lilly.com
`Lilly Corporate Center, 46285 Indianapolis, United States,
`Tel.: +1 317 651 2802; fax: +1 317 433 0448.
`
`Background: Atypical antipsychotic agents are increasingly pre-
`scribed for adolescent patients, but most, including olanzapine, are not
`approved for them. Relatively little information is available comparing
`spontaneously reported post-marketing adverse events in adolescents
`and adults.
`Methods: Spontaneous serious and nonserious adverse event reports
`from postmarketing experience in the Lilly Safety System were
`analyzed for adverse events occurring during olanzapine treatment
`through May 31, 2007. Proportional reporting ratios (PRR) and Chi-
`squares were calculated comparing adverse event frequencies in
`adolescents (13–17 years) and adults (18–64 years). Three criteria
`(≥1.0% frequency among all adolescent event reports, PRR≥2, and
`Chi-square ≥4) identified spontaneous adverse event report differ-
`ences between adolescents and adults.
`Results: Of total olanzapine spontaneous adverse events, 2.6% were
`reported in adolescents and 60.3% in adults. Remaining events
`included 9.0% in patients ≥65 years, 1.9% in patients b=12 years, and
`26.2% where age was not reported. The most frequent reasons for
`olanzapine use in adolescents were schizophrenia, psychotic disorder
`and bipolar I disorder. Four events met criteria for potential differences
`in event reporting for adolescents: somnolence, aggression, galactor-
`rhoea and sedation.
`Conclusions: Somnolence, aggression, galactorrhoea, and sedation
`were the event terms meeting criteria for a potential difference in
`reporting in adolescent versus adult patients. Since product launch
`cumulatively through May 31, 2007, somnolence was rarely reported
`(frequency ≥0.01% and b0.1%). aggression, galactorrhoea, and
`sedation were very rarely reported (frequency b0.01%) in adolescents.
`Caution is warranted interpreting spontaneous event data because
`patient medical information may be incomplete and reporting bias or
`underreporting may occur.
`
`doi:10.1016/j.schres.2007.12.388
`
`322 – EFFICACY/TOLERABILITY OF PALIPERIDONE
`PALMITATE: 9-WEEK, PLACEBO-CONTROLLED STUDY IN
`SCHIZOPHRENIA PATIENTS
`
`M. Kramer 1, R. Litman 2, R. Lane 3, M. Kujawa 1, P. Lim 1,
`D. Hough 1, M. Eerdekens 4.
`
`1Johnson & Johnson Pharmaceutical Research and Development,
`Titusville, NJ, USA
`2CBH Health, LLC, Rockville, Maryland, USA
`3Johnson & Johnson Pharmaceutical Research and Development,
`Raritan, NJ, USA
`4Johnson & Johnson Pharmaceutical Research and Development,
`Beerse, Belgium
`
`Presenting Author details: mkujawamd@aol.com
`1125 Trenton-Harbourton Road, 08560 Titusville, United States,
`Tel.: +1 609 730 2442.
`
`Background: This study evaluated the efficacy and safety of
`paliperidone palmitate, a long-acting injectable agent, in the treatment
`of patients with schizophrenia.
`Methods: A 9-week, double-blind, placebo-controlled study, rando-
`mized schizophrenia patients (N = 197 [intent-to-treat population],
`male=62%, mean±SD age =39.3±10.3 years) to receive placebo or
`
`Mylan v. Janssen (IPR2020-00440) Ex. 1039, p. 002
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`166
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`ABSTRACTS / Schizophrenia Research 98 (2008) 3–199
`
`paliperidone palmitate 50 or 100 mg eq. on Days 1, 8 and 36 (without oral
`supplementation). Efficacy and tolerability were evaluated via changes in
`mean Positive and Negative Syndrome Scale (PANSS) total scores
`(baseline=87.0±12.5) and adverse event (AE) reporting, respectively.
`Results: Mean ± SD PANSS total scores significantly improved
`(p≤0.001) from baseline to end point for paliperidone palmitate 50 mg
`eq. (−5.2 ±21.5) and 100 mg eq. (−7.8±19.4) versus placebo (+6.2
`±18.3), with significant improvements observed from Day 8. Responder
`rates (≥30% improvement
`in PANSS score at end point) were
`significantly greater in both paliperidone palmitate groups versus placebo
`(p≤0.007). AEs occurring ≥3% more with paliperidone palmitate than
`placebo (safety population, N=247) were insomnia, schizophrenia,
`restlessness, sedation, extrapyramidal disorder, hypertonia, attention
`disturbance, electrocardiogram abnormal, constipation, myalgia, asthenia
`and vertigo. EPS-AE rates were comparable for paliperidone palmitate
`and placebo, with the exception of parkinsonism (7% and 1%,
`respectively). Serious AEs in ≥1 patient in any group were schizophrenia
`and psychotic disorder. Other serious AEs included elevated hepatic
`enzymes (placebo, n=1), depression (50 mg eq., n=1), suicidal ideation
`(50 mg eq., n=1), psychomotor agitation (100 mg eq., n=1) and syncope
`(100 mg eq., n=1). No deaths occurred during the study.
`Conclusions: Paliperidone palmitate (50 and 100 mg eq. doses) was
`effective and well tolerated in acute symptomatic schizophrenia.
`Acknowledgement: Data previously presented at the U.S. Psychiatric
`& Mental Health Congress, 2007. Supported by funding from
`Johnson & Johnson Pharmaceutical Services, LLC, and Johnson &
`Johnson Pharmaceutical Research & Development.
`
`doi:10.1016/j.schres.2007.12.389
`
`323 – TAMOXIFEN — A POTENTIAL TREATMENT FOR
`WOMEN IN THE MANIC PHASE OF BIPOLAR AFFECTIVE
`DISORDER?
`
`J. Kulkarni 1, L. Mu 1, A. De Castella 1, C. Gurvich 1, P. Fitzgerald 1,
`S. Davis 2.
`
`1Alfred Psychiatry Research Centre, The Alfred Hospital and the
`School of Psychology, Psychiatry and Psychological Medicine,
`Monash University, Melbourne Australia
`2Department of Medicine, Alfred Hospital and Department of
`Obstetrics and Gynaecology, Faculty of Medicine, Nursing and
`Health Sciences, Monash University, Melbourne Australia
`
`Presenting Author details: j.kulkarni@alfred.org.au
`The Alfred Hospital, Level One, Old Baker Building, Commercial
`Road, 3004 Melbourne, Australia,
`Tel.: +61 3 9076 6924; fax: +61 3 9076 6588.
`
`Background: Bipolar Affective Disorder (BPAD) is an illness with high
`morbidity and mortality. Lithium and other mood stabilizers are the main
`treatments for BPAD, despite little being known about their mechanisms
`of action. Recent attempts to elucidate the biochemical actions of these
`drugs have focused on the Protein Kinase C (PKC) pathways. Another
`PKC inhibitor hypothesized to be effective in the treatment of mania is
`tamoxifen, a selective estrogen receptor modulator with estrogen receptor
`antagonist actions in the CNS. The aim of the current study was to
`compare the effectiveness of two adjunctive antiestrogen agents
`(tamoxifen and progesterone) to placebo in the treatment of acute mania.
`
`Methods: Women in the manic phase of BPAD or schizoaffective
`disorder were included in this 28-day, three-arm (40 mg/day oral
`tamoxifen or 20 mg/day oral progesterone or oral placebo) double-
`blind, placebo controlled and adjunctive study. All patients also
`received a mood stabilizer as the baseline treatment. Manic, psychotic
`and depressive symptoms were measured weekly using the Clinician
`Administered Rating Scale for Mania (CARS-M), Positive and
`Negative Syndrome Scale (PANSS) and Montgomery–Asberg
`Depression Rating Scale (MADRS) rating scales respectively, as
`were estrogen, progesterone and gonadotrophin levels. Cognitive
`functioning (RBANS) was assessed in a sub-sample of participants at
`baseline and repeated on day 28.
`Results: Results of 43 women indicated a decline in the symptoms of
`mania and psychopathology in the tamoxifen group and to a lesser extent
`in the progesterone and control groups.
`Conclusions: The results suggest that tamoxifen may be a useful adjunct
`in the treatment of acute manic symptoms in women with BPAD.
`Acknowledgements: This research is supported by The Stanley
`Medical Research Institute.
`
`doi:10.1016/j.schres.2007.12.390
`
`324 – ADEPT: A DEFINITIVE ESTROGEN PATCH TRIAL
`
`J. Kulkarni 1, C. Gurvich 1, F. Mehmedbegovic 1, A. De Castella 1,
`P. Ftizgerald 1, H. Burger 2.
`
`1The Alfred Psychiatry Research Centre, The Alfred and Monash
`University School of Psychology, Psychiatry and Psychological
`Medicine, Melbourne, Australia
`2Prince Henry's Institute, Monash Medical Centre, Melbourne, Australia
`
`Presenting Author details: j.kulkarni@alfred.org.au
`The Alfred Hospital, Level One, Old Baker Building, Commercial
`Road, 3004 Melbourne, Australia,
`Tel.: +61 3 9076 6924; fax: +61 3 9076 6588.
`
`Introduction: Accumulating evidence suggests estrogens may have
`therapeutic effects in severe mental illnesses, including schizophrenia, via
`neuromodulatory and neuroprotective activity. We will present the results of
`two research trials comparing the effectiveness of adjunctive transdermal
`estradiol (100 or 200 μg/day) to adjunctive placebo, in the treatment of
`acute psychotic symptoms.
`Methods: For the first study, women of childbearing age with a diagnosis
`of schizophrenia or schizoaffective disorder were invited to participate in
`a 4-week, double-blind, placebo controlled study. Women were
`randomized to receive either 100 mcg transdermal adjunctive estradiol
`(56 women), or adjunctive transdermal placebo (46 women), for a 28-day
`trial period (and all patients continued to receive their standard
`antipsychotic treatment). Assessments were conducted at baseline, then
`at days 7, 14, 21 and 28, and included psychopathology (PANSS) and
`mood (MADRS) ratings, as well as measures of estrogen, progesterone,
`and gonadotropin levels. A cognitive battery was also completed at each
`assessment. The subsequent trial is ongoing and involves a similar patient
`population, participating in an 8-week, three-arm (100 μg/day adjunctive
`transdermal estradiol, 200 μg/day adjunctive transdermal estradiol, or
`adjunctive transdermal placebo) double-blind, placebo controlled study.
`The previously described assessment battery is conducted at baseline,
`then at days 7, 14, 28 and 56.
`
`Mylan v. Janssen (IPR2020-00440) Ex. 1039, p. 003
`
`