- Email: [email protected]
37 – Long-term double-blind extension studies of asenapine vs. olanzapine in patients with bipolar mania
48
ABSTRACTS / Schizophrenia Research 98 (2008) 3–199
35 – LONG-TERM SAFETY OF ASENAPINE IN PATIENTS WITH SCHIZOPHRENIA R. Emsley 1, P. Den Doelder 2, J. Schoemaker 2, D. Naber 3. 1
University of Stellenbosch, Cape Town, South Africa Organon Biosciences, Global Clinical Development and Biometrics, Oss, The Netherlands 3 University of Hamburg-Eppendorf, Hamburg, Germany 2
Presenting Author details: [email protected] Martinistrasse 52, D-20246 Hamburg, Germany, Tel.: +49 40 42803 2205. Background: Asenapine is a novel psychopharmacologic agent under development for treatment of schizophrenia and bipolar mania. This trial focused on the long-term safety of asenapine in patients with schizophrenia. Methods: In this double-blind, non-US, 1-year-long Phase III trial, patients were randomly assigned (3:1) to asenapine, 10–20 mg, or olanzapine, 20–40 mg, daily. Safety assessments included adverse events (AEs), body weight, and laboratory examinations. Other assessments included the Subjective Well-Being on Neuroleptics (SWN) scale, Short Form (SF-12) health survey, and PANSS (using mixed model for repeated measures). Results: Among 1219 treated patients, the final dose was 10 mg/day for 53% and 59% of patients in the asenapine and olanzapine groups, respectively. Drug-related AEs (mostly mild-to-moderate) occurred in 60% and 61% of patients on asenapine and olanzapine, respectively; withdrawals due to serious AEs were similar (6.3% and 6.8%). Incidence of EPS was 18% and 8%; mean weight gain was 1.6 kg and 5.6 kg; significant weight gain (≥7%) was 14.7% with asenapine and 36.1% with olanzapine. In both groups, the incidence of QTcF N 500 ms or prolongation N60 ms was 0% and 0.3%. Both groups showed small mean declines in prolactin levels. Mean changes in fasting glucose, cholesterol, and triglycerides were small in both groups. Similar responses on SWN and SF-12 assessments were observed. The difference in PANSS total score between groups was 0.5 at week 6 and 4.2 points at week 52. Conclusions: Long-term treatment (1 year) with asenapine was well tolerated in patients with schizophrenia.
Background: Early onset bipolar disorder is often chronic and associated with significant comorbidity. There is a paucity of data from controlled trials in this patient population with which to guide treatment decisions. The long-term efficacy and safety of aripiprazole was assessed in pediatric bipolar patients. Methods: 296 youths, ages 10–17 years old with a DSM-IV diagnosis of bipolar I disorder were randomized to placebo or aripiprazole 10 mg or 30 mg in a 4-week double blind trial. Completers continued assigned treatments for 26 weeks (doubleblind). Efficacy endpoints included mean change from baseline to Week 30 on the Young Mania Rating Scale (YMRS), Children's Global Assessment Scale (CGAS), Clinical Global Impression Scale – Bipolar Version (CGI-BP) severity score, Children's Depression Rating Scale – Revised (CDRS-R), General Behavior Inventory (GBI), ADHD-RS-IV, time to discontinuation and response rate. Safety measures included frequency and severity of adverse events (AEs), Simpson and Angus Rating Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), blood chemistries and body weight. Results: In the double-blind continuation phase of this study, aripiprazole 10 mg and 30 mg groups demonstrated significant superiority to placebo at all visits through Week 30 on mean change from baseline in the YMRS total score (p b .0001). Significant improvements were observed on the CGAS, CGI-BP, ADHD-RS-IV total score, time to discontinuation (10 mg vs. placebo, p b 0.0001; 30 mg vs. placebo, p = 0.0124), and response rate (10 mg vs. placebo, p b .0001; and 30 mg vs. placebo, p b .0001). Most AEs were mild to moderate in severity. The most common AEs in the combined aripiprazole groups were extrapyramidal disorder, somnolence, and headache. Significant difference from placebo was observed on the SAS (30 mg), but not on the BARS at Week 30. Low prolactin levels were more frequent in aripiprazole treated patients. There was no clinically significant change in weight z-scores at end of study. Conclusions: Aripiprazole 10 mg and 30 mg doses were superior to placebo in the long term treatment of pediatric bipolar patients. Over 30 weeks, most AEs were mild or moderate. doi:10.1016/j.schres.2007.12.103
37 – LONG-TERM DOUBLE-BLIND EXTENSION STUDIES OF ASENAPINE VS. OLANZAPINE IN PATIENTS WITH BIPOLAR MANIA
doi:10.1016/j.schres.2007.12.102
36 – LONG-TERM EFFICACY AND SAFETY OF ARIPIPRAZOLE IN PEDIATRIC PATIENTS WITH BIPOLAR I DISORDER
R. McIntyre 1, L. Alphs 2, M. Cohen 3, D.S. Keller 4, T. Macek 2, J. Panagides 5. 1
1
1
1
1
1
M. Nyilas , W. Carson , R. Forbes , S. Ashfaque , R. McQuade , R. Owen 2, E. Weller 3, C. Correll 4. 1
University of Toronto, Canada Employed at Pfizer Inc. at the time of this research 3 Organon Biosciences, Roseland, NJ, USA 4 Pfizer Global R&D, Groton, CT, USA 5 Organon International Inc, Roseland, NJ, USA 2
Otsuka Pharmaceutical Development and Commercialization, Princeton, NJ, USA 2 Bristol Myers-Squibb, Wallingford, CT, USA 3 Children's Hospital for Active Treatment, Philadelphia, PA, USA 4 Stony Brook University School of Medicine, Stony Brook, NY, USA
Presenting Author details: [email protected] 399 Bathurst Street, MP 9-325, M5T 2S8 Toronto, Ontario, Canada, Tel.: +1 416 603 5279.
Presenting Author details: [email protected] 100 Overlook Dr., 08540 Princeton, United States, Tel.: +1 609 452 5673; fax: +1 240 399 6221.
Background: Asenapine is a novel psychopharmacologic agent under development for the treatment of schizophrenia and bipolar disorder. We assessed asenapine versus olanzapine in bipolar mania.
ABSTRACTS / Schizophrenia Research 98 (2008) 3–199 Methods: Bipolar I patients who completed a 3-week placebocontrolled trial of asenapine (with olanzapine as active control) were eligible for a 9-week double-blind extension study; those who completed the 9-week extension were eligible for an additional 40week extension focusing on safety (total treatment period, 1 year). Study drugs were initiated at the maintenance dosages used in the 3week trial; flexible dose asenapine (5–10 mg BID) or olanzapine (5– 20 mg QD). Efficacy was measured using the Young Mania Rating Scale (YMRS) and calculating changes from baseline as well as rates of responders and remitters. Results: In the 9-week extension (N = 504), mean change from baseline in YMRS total score was 24.4 with asenapine vs. 23.9 with olanzapine. Prespecified statistical analysis for non-inferiority indicated no significant differences between asenapine and olanzapine. In the 40-week extension (N = 218), comparable efficacy was maintained. More than 90% of patients in both groups showed response (YMRS total score reduced by ≥50%) or remission (total score ≤ 12). Completion rates and discontinuations were similar between groups. Incidence rates of treatment-related adverse events were 65.7% for asenapine and 61.7% for olanzapine; weight gain, metabolic syndrome (NCEP-ATP-III criteria) and prolactin elevation were more common with olanzapine, whereas extrapyramidal symptoms were more common with asenapine. Conclusions: These studies demonstrate long-term efficacy for asenapine, comparable to olanzapine in bipolar mania, with a favorable tolerability profile for asenapine.
49
Results: The risk for diabetes and total CHD events was lower for patients treated with ziprasidone compared with other atypical antipsychotics. Similarly, ziprasidone was associated with the lowest costs for treatment of diabetes and total CHD events (US $5835 and $1599, respectively) versus olanzapine (US $6276 and $1884, respectively), risperidone (US $5994 and $1670, respectively), and quetiapine (US $5993 and $1751, respectively). Although the risk for psychiatric hospitalizations was lowest among patients treated with olanzapine, the estimated total cost of olanzapine treatment was the highest of the atypical antipsychotics evaluated. Sensitivity analyses indicate that the model, overall, is robust. Conclusions: The long-term metabolic consequences of some atypical antipsychotics are not only deleterious for patients with the potential for developing diabetes and CHD, but may also place an additional economic burden on the healthcare system in terms of total costs and resource utilization. doi:10.1016/j.schres.2007.12.105
39 – ARIPIPRAZOLE IN COMBINATION WITH AIRCRYOTHERAPY FOR TREATMENT OF SCHIZOPHRENIA IN BREAST CANCER PATIENTS V. Sushko 1,2.
doi:10.1016/j.schres.2007.12.104
38 – CLINICAL AND ECONOMIC OUTCOMES OF ATYPICAL ANTIPSYCHOTICS IN SCHIZOPHRENIA S.V. Sonja 1, H.A. Nasrallah 2, L.S. Craigin 1, T.M. Baker 1, J. Harnett 3, K.N. Sanders 3, C. Kremer 3. 1
United Biosource Corporation, Bethesda, MD, USA Department of Psychiatry, University of Cincinnati, Cincinnati, OH, USA 3 Pfizer Inc., New York, NY, USA 2
Presenting Author details: [email protected] Pfizer Inc., 235 East 42nd Street, 10th Floor, 20814 New York, NY, United States, Tel.: +1 212 733 2957; fax: +1 212 733 2900. Background: To evaluate the expected long-term risk and associated costs of developing diabetes and cardiovascular complications with prolonged atypical antipsychotic treatment in a cohort of patients with chronic schizophrenia in the United States. Methods: A simulation was conducted of the 10-year risk for primary and secondary CHD events and new-onset diabetes. This incorporated exposure-adjusted metabolic changes from the CATIE study and risk equations from the Framingham Heart Study for CHD and national epidemiologic surveys for diabetes. Number needed to harm and relative risk were calculated in addition to overall treatment costs, which included costs for CHD events, diabetes, psychiatric hospitalizations (from CATIE) as well as adverse events, medication utilization, and monitoring. Probabilistic and one-way sensitivity analyses were also conducted.
1 Department of Psychiatry, Odessa State Medical University, Odessa, Ukraine 2 Odessa Regional Cancer Hospital, Odessa, Ukraine
Presenting Author details: [email protected] 9 Str. Transportnaya 21, 65039 Odessa, Ukraine, Tel.: +380 0482 68 76 23. Background: Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia. Hyperprolactinaemia is a frequent side-effect in the use of atypical antipsychotics. The endocrine and sexual side effects related to hyperprolactinaemia significantly impair in breast cancer patients. Methods: The effect combination of a low dose aripiprazole and whole-body cold therapy and quality of life were examined in a sample of 21 breast cancer patients who had schizophrenia. They were randomly assigned to experimental or control groups. They were interviewed by psychiatrists and tested using Positive and Negative Syndrome Scale (PANSS) and Quality of Life Questionnaire (QOLQ) at baseline and follow-up visits. Plasma prolactin level was assessed at baseline and at the end of the study. Each received aripiprazole as their sole antipsychotic agent at a maximum dose of 20 mg once daily. The patients experimental group had aircryotherapy as a whole-body cold therapy (with cold air cooled by addition of nitrogen blew on the patients in an open cabin). The patients were treated one and a half minutes on average in the chamber (mean temperature: − 150 °C). At least several sessions of aircryotherapy, usually given at the rate of three per week, are required for full therapeutic benefit. Results: The results of our study suggest that after 3 weeks of schizophrenia treatment 90.9% of patients from the experimental group and 50% from the control group showed significant clinical improvement. According to the results of our study, there is evidence that the whole-body cold therapy in combination with aripiprazole
ABSTRACTS / Schizophrenia Research 98 (2008) 3–199
35 – LONG-TERM SAFETY OF ASENAPINE IN PATIENTS WITH SCHIZOPHRENIA R. Emsley 1, P. Den Doelder 2, J. Schoemaker 2, D. Naber 3. 1
University of Stellenbosch, Cape Town, South Africa Organon Biosciences, Global Clinical Development and Biometrics, Oss, The Netherlands 3 University of Hamburg-Eppendorf, Hamburg, Germany 2
Presenting Author details: [email protected] Martinistrasse 52, D-20246 Hamburg, Germany, Tel.: +49 40 42803 2205. Background: Asenapine is a novel psychopharmacologic agent under development for treatment of schizophrenia and bipolar mania. This trial focused on the long-term safety of asenapine in patients with schizophrenia. Methods: In this double-blind, non-US, 1-year-long Phase III trial, patients were randomly assigned (3:1) to asenapine, 10–20 mg, or olanzapine, 20–40 mg, daily. Safety assessments included adverse events (AEs), body weight, and laboratory examinations. Other assessments included the Subjective Well-Being on Neuroleptics (SWN) scale, Short Form (SF-12) health survey, and PANSS (using mixed model for repeated measures). Results: Among 1219 treated patients, the final dose was 10 mg/day for 53% and 59% of patients in the asenapine and olanzapine groups, respectively. Drug-related AEs (mostly mild-to-moderate) occurred in 60% and 61% of patients on asenapine and olanzapine, respectively; withdrawals due to serious AEs were similar (6.3% and 6.8%). Incidence of EPS was 18% and 8%; mean weight gain was 1.6 kg and 5.6 kg; significant weight gain (≥7%) was 14.7% with asenapine and 36.1% with olanzapine. In both groups, the incidence of QTcF N 500 ms or prolongation N60 ms was 0% and 0.3%. Both groups showed small mean declines in prolactin levels. Mean changes in fasting glucose, cholesterol, and triglycerides were small in both groups. Similar responses on SWN and SF-12 assessments were observed. The difference in PANSS total score between groups was 0.5 at week 6 and 4.2 points at week 52. Conclusions: Long-term treatment (1 year) with asenapine was well tolerated in patients with schizophrenia.
Background: Early onset bipolar disorder is often chronic and associated with significant comorbidity. There is a paucity of data from controlled trials in this patient population with which to guide treatment decisions. The long-term efficacy and safety of aripiprazole was assessed in pediatric bipolar patients. Methods: 296 youths, ages 10–17 years old with a DSM-IV diagnosis of bipolar I disorder were randomized to placebo or aripiprazole 10 mg or 30 mg in a 4-week double blind trial. Completers continued assigned treatments for 26 weeks (doubleblind). Efficacy endpoints included mean change from baseline to Week 30 on the Young Mania Rating Scale (YMRS), Children's Global Assessment Scale (CGAS), Clinical Global Impression Scale – Bipolar Version (CGI-BP) severity score, Children's Depression Rating Scale – Revised (CDRS-R), General Behavior Inventory (GBI), ADHD-RS-IV, time to discontinuation and response rate. Safety measures included frequency and severity of adverse events (AEs), Simpson and Angus Rating Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), blood chemistries and body weight. Results: In the double-blind continuation phase of this study, aripiprazole 10 mg and 30 mg groups demonstrated significant superiority to placebo at all visits through Week 30 on mean change from baseline in the YMRS total score (p b .0001). Significant improvements were observed on the CGAS, CGI-BP, ADHD-RS-IV total score, time to discontinuation (10 mg vs. placebo, p b 0.0001; 30 mg vs. placebo, p = 0.0124), and response rate (10 mg vs. placebo, p b .0001; and 30 mg vs. placebo, p b .0001). Most AEs were mild to moderate in severity. The most common AEs in the combined aripiprazole groups were extrapyramidal disorder, somnolence, and headache. Significant difference from placebo was observed on the SAS (30 mg), but not on the BARS at Week 30. Low prolactin levels were more frequent in aripiprazole treated patients. There was no clinically significant change in weight z-scores at end of study. Conclusions: Aripiprazole 10 mg and 30 mg doses were superior to placebo in the long term treatment of pediatric bipolar patients. Over 30 weeks, most AEs were mild or moderate. doi:10.1016/j.schres.2007.12.103
37 – LONG-TERM DOUBLE-BLIND EXTENSION STUDIES OF ASENAPINE VS. OLANZAPINE IN PATIENTS WITH BIPOLAR MANIA
doi:10.1016/j.schres.2007.12.102
36 – LONG-TERM EFFICACY AND SAFETY OF ARIPIPRAZOLE IN PEDIATRIC PATIENTS WITH BIPOLAR I DISORDER
R. McIntyre 1, L. Alphs 2, M. Cohen 3, D.S. Keller 4, T. Macek 2, J. Panagides 5. 1
1
1
1
1
1
M. Nyilas , W. Carson , R. Forbes , S. Ashfaque , R. McQuade , R. Owen 2, E. Weller 3, C. Correll 4. 1
University of Toronto, Canada Employed at Pfizer Inc. at the time of this research 3 Organon Biosciences, Roseland, NJ, USA 4 Pfizer Global R&D, Groton, CT, USA 5 Organon International Inc, Roseland, NJ, USA 2
Otsuka Pharmaceutical Development and Commercialization, Princeton, NJ, USA 2 Bristol Myers-Squibb, Wallingford, CT, USA 3 Children's Hospital for Active Treatment, Philadelphia, PA, USA 4 Stony Brook University School of Medicine, Stony Brook, NY, USA
Presenting Author details: [email protected] 399 Bathurst Street, MP 9-325, M5T 2S8 Toronto, Ontario, Canada, Tel.: +1 416 603 5279.
Presenting Author details: [email protected] 100 Overlook Dr., 08540 Princeton, United States, Tel.: +1 609 452 5673; fax: +1 240 399 6221.
Background: Asenapine is a novel psychopharmacologic agent under development for the treatment of schizophrenia and bipolar disorder. We assessed asenapine versus olanzapine in bipolar mania.
ABSTRACTS / Schizophrenia Research 98 (2008) 3–199 Methods: Bipolar I patients who completed a 3-week placebocontrolled trial of asenapine (with olanzapine as active control) were eligible for a 9-week double-blind extension study; those who completed the 9-week extension were eligible for an additional 40week extension focusing on safety (total treatment period, 1 year). Study drugs were initiated at the maintenance dosages used in the 3week trial; flexible dose asenapine (5–10 mg BID) or olanzapine (5– 20 mg QD). Efficacy was measured using the Young Mania Rating Scale (YMRS) and calculating changes from baseline as well as rates of responders and remitters. Results: In the 9-week extension (N = 504), mean change from baseline in YMRS total score was 24.4 with asenapine vs. 23.9 with olanzapine. Prespecified statistical analysis for non-inferiority indicated no significant differences between asenapine and olanzapine. In the 40-week extension (N = 218), comparable efficacy was maintained. More than 90% of patients in both groups showed response (YMRS total score reduced by ≥50%) or remission (total score ≤ 12). Completion rates and discontinuations were similar between groups. Incidence rates of treatment-related adverse events were 65.7% for asenapine and 61.7% for olanzapine; weight gain, metabolic syndrome (NCEP-ATP-III criteria) and prolactin elevation were more common with olanzapine, whereas extrapyramidal symptoms were more common with asenapine. Conclusions: These studies demonstrate long-term efficacy for asenapine, comparable to olanzapine in bipolar mania, with a favorable tolerability profile for asenapine.
49
Results: The risk for diabetes and total CHD events was lower for patients treated with ziprasidone compared with other atypical antipsychotics. Similarly, ziprasidone was associated with the lowest costs for treatment of diabetes and total CHD events (US $5835 and $1599, respectively) versus olanzapine (US $6276 and $1884, respectively), risperidone (US $5994 and $1670, respectively), and quetiapine (US $5993 and $1751, respectively). Although the risk for psychiatric hospitalizations was lowest among patients treated with olanzapine, the estimated total cost of olanzapine treatment was the highest of the atypical antipsychotics evaluated. Sensitivity analyses indicate that the model, overall, is robust. Conclusions: The long-term metabolic consequences of some atypical antipsychotics are not only deleterious for patients with the potential for developing diabetes and CHD, but may also place an additional economic burden on the healthcare system in terms of total costs and resource utilization. doi:10.1016/j.schres.2007.12.105
39 – ARIPIPRAZOLE IN COMBINATION WITH AIRCRYOTHERAPY FOR TREATMENT OF SCHIZOPHRENIA IN BREAST CANCER PATIENTS V. Sushko 1,2.
doi:10.1016/j.schres.2007.12.104
38 – CLINICAL AND ECONOMIC OUTCOMES OF ATYPICAL ANTIPSYCHOTICS IN SCHIZOPHRENIA S.V. Sonja 1, H.A. Nasrallah 2, L.S. Craigin 1, T.M. Baker 1, J. Harnett 3, K.N. Sanders 3, C. Kremer 3. 1
United Biosource Corporation, Bethesda, MD, USA Department of Psychiatry, University of Cincinnati, Cincinnati, OH, USA 3 Pfizer Inc., New York, NY, USA 2
Presenting Author details: [email protected] Pfizer Inc., 235 East 42nd Street, 10th Floor, 20814 New York, NY, United States, Tel.: +1 212 733 2957; fax: +1 212 733 2900. Background: To evaluate the expected long-term risk and associated costs of developing diabetes and cardiovascular complications with prolonged atypical antipsychotic treatment in a cohort of patients with chronic schizophrenia in the United States. Methods: A simulation was conducted of the 10-year risk for primary and secondary CHD events and new-onset diabetes. This incorporated exposure-adjusted metabolic changes from the CATIE study and risk equations from the Framingham Heart Study for CHD and national epidemiologic surveys for diabetes. Number needed to harm and relative risk were calculated in addition to overall treatment costs, which included costs for CHD events, diabetes, psychiatric hospitalizations (from CATIE) as well as adverse events, medication utilization, and monitoring. Probabilistic and one-way sensitivity analyses were also conducted.
1 Department of Psychiatry, Odessa State Medical University, Odessa, Ukraine 2 Odessa Regional Cancer Hospital, Odessa, Ukraine
Presenting Author details: [email protected] 9 Str. Transportnaya 21, 65039 Odessa, Ukraine, Tel.: +380 0482 68 76 23. Background: Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia. Hyperprolactinaemia is a frequent side-effect in the use of atypical antipsychotics. The endocrine and sexual side effects related to hyperprolactinaemia significantly impair in breast cancer patients. Methods: The effect combination of a low dose aripiprazole and whole-body cold therapy and quality of life were examined in a sample of 21 breast cancer patients who had schizophrenia. They were randomly assigned to experimental or control groups. They were interviewed by psychiatrists and tested using Positive and Negative Syndrome Scale (PANSS) and Quality of Life Questionnaire (QOLQ) at baseline and follow-up visits. Plasma prolactin level was assessed at baseline and at the end of the study. Each received aripiprazole as their sole antipsychotic agent at a maximum dose of 20 mg once daily. The patients experimental group had aircryotherapy as a whole-body cold therapy (with cold air cooled by addition of nitrogen blew on the patients in an open cabin). The patients were treated one and a half minutes on average in the chamber (mean temperature: − 150 °C). At least several sessions of aircryotherapy, usually given at the rate of three per week, are required for full therapeutic benefit. Results: The results of our study suggest that after 3 weeks of schizophrenia treatment 90.9% of patients from the experimental group and 50% from the control group showed significant clinical improvement. According to the results of our study, there is evidence that the whole-body cold therapy in combination with aripiprazole