Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00190749
First received: September 12, 2005
Last updated: April 26, 2010
Last verified: April 2010

September 12, 2005
April 26, 2010
October 2003
June 2008   (final data collection date for primary outcome measure)
Change in Baseline to Last Observation In Normalized Insulin Sensitivity Index at Low Insulin Phase Using Change in Weight as a Covariate [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
Normalized insulin sensitivity index (Mffm/I) was defined as the ratio of whole body glucose disposal rate normalized to fat-free mass (Mffm) divided by the plasma insulin concentration (I) during steady-state conditions of the clamp procedure. Units:[(mg glucose)*min*mL] / [(kg fat free body mass)*(micro IU insulin)]
  • -Assess if olanzapine and risperidone are associated with a significant within-treatment group change in insulin sensitivity over 12-week period as measured by rinsulinemic euglycemic clamp.
  • -For the primary and key secondary analyses, insulin sensitivity will be measured by the insulin sensitivity index ([mean glucose infusion rate/fat free mass]/mean insulin concentration)determined
  • at steady state during the low insulin infusion phase of a two-step hyperinsulinemic euglycemic clamp.
Complete list of historical versions of study NCT00190749 on ClinicalTrials.gov Archive Site
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Weight. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in weight
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Body Mass Index (BMI) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in BMI
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Ratio of Visceral Fat Area to the Subcutaneous Fat Area. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in ratio of visceral far area to subcutaneous fat area
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Brief Psychiatric Rating Scale Scores. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin senstivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Brief Psychiatric Rating Scale scores
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Clinical Global Impression - Severity of Illness Scale Scores. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Clinical Global Impression-Severity of Illness scale scores
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Abnormal Involuntary Movement Scale Scores. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Abnormal Involuntary Movement Scale scores
  • Pairwise Correlation Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Barnes Akathisia Scale Scores. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Barnes Akathisia scores
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in the Simpson Angus Scale Scores. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in the Simpson Angus Scale scores
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Waist Circumference. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in waist circumference
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Visceral Fat Area. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in visceral fat area
  • Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Subcutaneous Fat Area. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in subcutaneous fat area
  • Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Eating Behavior Assessment Scale scores
  • Change From Baseline to 12 Week Endpoint in Body Mass Index [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Within-and Between-Treatment Group changes in Body Mass Index from baseline to last observation carried forward.
  • Change From Baseline to 12 Week Endpoint in Weight [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Weight change from baseline to last visit (last observation carried forward)
  • Change From Baseline to 12 Week Endpoint in Waist Circumference [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Waist circumference change from baseline to last observation carried forward.
  • Change From Baseline to 12 Week Endpoint in Visceral Fat Area [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Visceral fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period
  • Change From Baseline to 12 Week Endpoint in Subcutaneous Fat Area [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Subcutaneous fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period
  • Change From Baseline to 12 Week Endpoint in the Ratio of the Visceral Fat Area to the Subcutaneous Fat Area [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Ratio of the visceral fat area to the subcutaneous fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period
  • Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Brief Psychiatric Rating Scale (BPRS) is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. Item scores range from 0 (not present) to 6 (extremely severe). Total Scores range from 0 to 108; Positive Subscale Scores range from 0 to 24. Negative Subscale Scores range from 0 to 18. Anxiety-Depression Subscale Scores range from 0 to 24.
  • Change From Baseline to 12 Week Endpoint in Clinical Global Impression - Severity of Illness Scores [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients.
  • Change From Baseline to 12 Week Endpoint in Abnormal Involuntary Movement Scale Scores [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    A 12-item instrument assesses observed abnormal movements in different parts of body. Seven items are scored in a 5-point scale (0 = none/normal, 4 = severe) which evaluates abnormal movements in 3 main anatomic areas (orofacial area, extremities, and trunk). Total scores range from 0 to 28. Five collected elements are not used in this total.
  • Change From Baseline to 12 Week Endpoint in Barnes Akathisia Rating Scale (BARS) Scores [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    The BARS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 is the Global clinical assessment and is rated 0 to 5 (0 = absent, 5 = severe). The other 3 items (related to objective and subjective assessments) are not used for these analyses.
  • Change From Baseline to 12 Week Endpoint in Simpson Angus Scale Scores [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Measures neuroleptic-induced parkinsonism. Total score of Simpson Angus Scale consists of the sum of 10 items rated on a 5-point severity scale where 0=normal and 4=extreme. The total score ranges from 0 to 40.
  • Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Eating Behavior Assessment Scale is a 9-item self-rated tool used to evaluate appetite and eating behaviors. Item scores range from 0 (never) to 4 (always).
  • Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Total Cholesterol [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Fasting lipid parameters including total cholesterol, change from baseline to last observation carried forward.
  • Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Direct Low Density Lipoprotein (LDL) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Fasting lipid parameters including Direct LDL, change from baseline to last observation carried forward.
  • Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including High Density Lipoprotein (HDL) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Fasting lipid parameters including HDL change from baseline to last observation carried forward.
  • Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Triglycerides [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: Yes ]
    Changes in fasting lipid parameters including triglycerides last observation carried forward (LOCF) mean change from baseline
  • Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses [ Time Frame: baseline and 12 weeks. ] [ Designated as safety issue: Yes ]
    Changes in lipid parameters and subclass lipoproteins last observation carried forward (LOCF) mean change from baseline. HDL=High Density Lipoprotein, IDL=Intermdiate Density Lipoprotein, LDL=Low Density Lipoprotein, VLDL=Very Low Density Lipoprotein.
  • -Comparison of effects of olanzapine vs. risperidone on the change in insulin sensitivity index from baseline to endpoint.
  • -Evaluation for each treatment group of the relationships between change in insulin sensitivity index and changes in:
  • weight, BMI, waist circumference, visceral fat area, subcutaneous fat area, ratio of visceral fat area to subcutaneous fat area.
  • -Evaluation for each treatment group of the relationship between change in insulin sensitivity index and changes in:
  • BPRS, CGI-S, AIMS, Barnes Akathisia, Simpson-Angus Scale and Eating Behavior Assessment Scale.
  • -Evaluation of within-treatment group and between-treatment groups changes in: BMI, weight, waist circumference, visceral fat area,
  • subcutaneous fat area, ratio of visceral fat area to subcutaneous fat area,
  • BPRS, CGI-S, AIMS, BAS, Simpson-Angus Scale, Eating Behavior Assessment Scale for olanzapine and risperidone.
  • -Evaluate the within-treatment group and between-treatment group changes in fasting lipid parameters for olanzapine and risperidone.
Not Provided
Not Provided
 
Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder
Insulin Sensitivity in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine and Risperidone

This study will assess whether olanzapine and/or risperidone affect the way the human body uses sugar in the blood.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Schizoaffective Disorder
  • Drug: olanzapine
    5-20 mg, oral, capsules, daily, 12 weeks.
    Other Names:
    • LY170053
    • Zyprexa
  • Drug: risperidone
    2-6 mg, oral, capsules, twice daily (BID), 12 weeks.
  • Experimental: Olanzapine
    Intervention: Drug: olanzapine
  • Active Comparator: Risperidone
    Intervention: Drug: risperidone
Case M, Treuer T, Karagianis J, Hoffmann VP. The potential role of appetite in predicting weight changes during treatment with olanzapine. BMC Psychiatry. 2010 Sep 14;10:72.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
130
June 2008
June 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 18-65 years old
  • Diagnosed with Schizophrenia or Schizoaffective disorder
  • Ability to visit the doctor's office for scheduled visits

Exclusion Criteria:

  • Women who are pregnant or breastfeeding
  • Have a body mass index (BMI) greater than 40
  • Have diabetes, heart disease or any other unstable illness
  • Have known positive human immunodeficiency virus (HIV)
  • Are currently taking olanzapine, risperidone, clozapine, glucocorticoids, injectable antipsychotics
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00190749
5296, F1D-MC-S014
No
Chief Medical Officer, Eli Lilly
Eli Lilly and Company
Not Provided
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP