Ziprasidone for Clozapine- or Olanzapine-Associated Diabetes Mellitus

Phase 4 Completed 24 enrolled North Suffolk Mental Health Association Pfizer · collab

NaSingle-groupOpen-labelTreatment

Summary

This study is a six-week, open label trial of the novel antipsychotic agent, ziprasidone, added to a stable dose of clozapine or olanzapine in 40 diabetes mellitus patients, patients with an impaired fasting glucose or insulin resistance with schizophrenia or schizoaffective disorder. The first two weeks will be a fixed-dose of ziprasidone 40 mg twice a day. During weeks 2-6, the ziprasidone dose may be increased up to 80 mg twice a day.

Timeline

Start: 2005-01
Primary completion: —
Completion: 2007-03

Outcome

Missed primary endpoint

registry p = 0.956; t-test, 2 sided NCT00351000 ↗

registry p = 0.988; t-test, 2 sided NCT00351000 ↗

Publications

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Background Caro JJ, Ward A, Levinton C, Robinson K. The risk of diabetes during olanzapine use compared with risperidone use: a retrospective database analysis. J Clin Psychiatry. 2002 Dec;63(12):1135-9. doi: 10.4088/jcp.v63n1208.
Background Cohen S, Fitzgerald B, Okos A, Khan S, Khan A. Weight, lipids, glucose, and behavioral measures with ziprasidone treatment in a population with mental retardation. J Clin Psychiatry. 2003 Jan;64(1):60-2. doi: 10.4088/jcp.v64n0112.
Background Colli A, Cocciolo M, Francobandiera F, Rogantin F, Cattalini N. Diabetic ketoacidosis associated with clozapine treatment. Diabetes Care. 1999 Jan;22(1):176-7. doi: 10.2337/diacare.22.1.176a. No abstract available.
Background Daniel DG, Copeland LF. Ziprasidone: comprehensive overview and clinical use of a novel antipsychotic. Expert Opin Investig Drugs. 2000 Apr;9(4):819-28. doi: 10.1517/13543784.9.4.819.
Background Gianfrancesco FD, Grogg AL, Mahmoud RA, Wang RH, Nasrallah HA. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002 Oct;63(10):920-30. doi: 10.4088/jcp.v63n1010.
Background Goodnick PJ. Ziprasidone: profile on safety. Expert Opin Pharmacother. 2001 Oct;2(10):1655-62. doi: 10.1517/14656566.2.10.1655.
Background Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996 Mar;153(3):321-30. doi: 10.1176/ajp.153.3.321.
Background Hagg S, Joelsson L, Mjorndal T, Spigset O, Oja G, Dahlqvist R. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry. 1998 Jun;59(6):294-9. doi: 10.4088/jcp.v59n0604.
Background HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.
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Background Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000 Jun;157(6):975-81. doi: 10.1176/appi.ajp.157.6.975.
Background Kato MM, Goodnick PJ. Antipsychotic medication: effects on regulation of glucose and lipids. Expert Opin Pharmacother. 2001 Oct;2(10):1571-82. doi: 10.1517/14656566.2.10.1571.
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Background Koller E, Schneider B, Bennett K, Dubitsky G. Clozapine-associated diabetes. Am J Med. 2001 Dec 15;111(9):716-23. doi: 10.1016/s0002-9343(01)01000-2.
Background Koller EA, Doraiswamy PM. Olanzapine-associated diabetes mellitus. Pharmacotherapy. 2002 Jul;22(7):841-52. doi: 10.1592/phco.22.11.841.33629.
Background Levine J, Schooler NR. SAFTEE: a technique for the systematic assessment of side effects in clinical trials. Psychopharmacol Bull. 1986;22(2):343-81. No abstract available.
Background Melkersson KI, Hulting AL, Brismar KE. Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses. J Clin Psychiatry. 2000 Oct;61(10):742-9. doi: 10.4088/jcp.v61n1006.
Background Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, Selke G. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002 Apr;59(4):337-45. doi: 10.1001/archpsyc.59.4.337.
Background Nuechterlein KH, Dawson ME, Gitlin M, Ventura J, Goldstein MJ, Snyder KS, Yee CM, Mintz J. Developmental Processes in Schizophrenic Disorders: longitudinal studies of vulnerability and stress. Schizophr Bull. 1992;18(3):387-425. doi: 10.1093/schbul/18.3.387.
Background Opp D, Hildebrandt C. Olanzapine-associated type 2 diabetes mellitus. Schizophr Res. 2002 Jul 1;56(1-2):195-6. doi: 10.1016/s0920-9964(01)00226-2. No abstract available.
Background Pi-Sunyer FX. Medical hazards of obesity. Ann Intern Med. 1993 Oct 1;119(7 Pt 2):655-60. doi: 10.7326/0003-4819-119-7_part_2-199310011-00006.
Background Seaburg HL, McLendon BM, Doraiswamy PM. Olanzapine-associated severe hyperglycemia, ketonuria, and acidosis: case report and review of literature. Pharmacotherapy. 2001 Nov;21(11):1448-54. doi: 10.1592/phco.21.17.1448.34421.
Background Spivak B, Alamy SS, Jarskog LF, Sheitman BB, Lieberman JA. Ziprasidone alternative for olanzapine-induced hyperglycemia. Am J Psychiatry. 2002 Sep;159(9):1606. doi: 10.1176/appi.ajp.159.9.1606. No abstract available.
Background Taylor D. Ziprasidone in the management of schizophrenia : the QT interval issue in context. CNS Drugs. 2003;17(6):423-30. doi: 10.2165/00023210-200317060-00004.
Background Wetterling T. Bodyweight gain with atypical antipsychotics. A comparative review. Drug Saf. 2001 Jan;24(1):59-73. doi: 10.2165/00002018-200124010-00005.
Background Wilson DR, D'Souza L, Sarkar N, Newton M, Hammond C. New-onset diabetes and ketoacidosis with atypical antipsychotics. Schizophr Res. 2003 Jan 1;59(1):1-6. doi: 10.1016/s0920-9964(01)00331-0.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ziprasidone	Small molecule	80 mg	—