A Study of Olanzapine in Patients With Schizophrenia

Official Title: “A Double-Blind Confirmatory Study Comparing Rapid-Acting Intramuscular Olanzapine and Rapid-Acting Intramuscular Placebo in Patients With an Exacerbation of Schizophrenia With Acute Psychotic Agitation”

The primary objectives of the study is to confirm if the efficacy of intramuscular injection (IM) olanzapine 10 mg in patients with an exacerbation of schizophrenia with acute psychotic agitation is greater than intramuscular placebo by comparing changes from baseline to 2 hours after the first IM injection of agitation.

Intervention(s) in this Clinical Trial

• Drug: Rapid-Acting Intramuscular Olanzapine
  • Administered via intramuscular injection (IM), possibility of second 10mg injection 2 to 4 hours after first injection, for a maximum of two injections
• Drug: Placebo
  • Administered via intramuscular injection (IM), possibility of second injection 2 to 4 hours after first injection, for a maximum of two injections

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 10mg Olanzapine
• Placebo Comparator: Placebo

Primary Measures

• Changes from baseline in Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) total score
  • Time Frame: Baseline, to 2 hours after first injection
    Safety Issue?: No

Secondary Measures

• Percentage of change from baseline in PANSS-EC total score
  • Time Frame: Baseline, 15 minutes, 30 minutes, 60 minutes, and 90 minutes after the first injection
    Safety Issue?: No
• Rate of responder
  • Time Frame: 2 hours after the first injection
    Safety Issue?: No
• Changes from baseline in Agitation-Calmness Evaluation Scale (ACES) score
  • Time Frame: Baseline, 30 minutes, 60 minutes, 90 minutes and 2 hours after the first injection, and 24 hours after first injection
    Safety Issue?: Yes
• Proportion of Drug Induced Extra-pyramidal Symptoms Scale (DIEPSS) score
  • Time Frame: Baseline through 24 hours after the first injection
    Safety Issue?: Yes
• Change from baseline in PANSS-EC total score
  • Time Frame: Baseline through 24 hours after first injection
    Safety Issue?: No

Inclusion Criteria:

• Patients who meet Diagnostic and Statistical Manual of Mental Disorders Fourth
• Edition Text Revision (DSM-IV-TR) criteria for schizophrenia.
• Patients with an exacerbation of schizophrenia with acute psychotic agitation.
• Patients who are hospitalized during the study.
• Patients, or proxy consenters, understand the nature of the study and sign on an informed consent document.
• The investigator or sub-investigator(s) judges that the patients are able to cooperate with all protocol procedures.
• Patients who are considered to be with agitation and appropriate candidates for treatment with IM medication by the investigator or sub-investigator(s).
• The investigator or sub-investigator(s) believes that it is safe to administer IM olanzapine to the patients in consideration of safety, including the anticholinergic action of IM olanzapine.
• Patients who have a score of 1 or 2 on ACES before the first IM injection of investigational product.

Exclusion Criteria:

• Patients whose Global Assessment of Functioning (GAF) score is less than or equal to 40 within last 1 year before informed consent.
• Patients with defect.
• Patients whose agitation continues more than 2 weeks before informed consent.
• Patients who were previously treated with antipsychotics and were considered by the investigator or sub-investigator(s) to be treatment-resistant to antipsychotics.
• Patients who were treated by oral olanzapine at a dose of more than 20 mg for more than 4 weeks but did not improve.
• Patient who have a history of participation in clozapine trials or treatment with clozapine.
• Patients who have co-morbidity of mental retardation and personality disorder.
• Patients whose agitation is possibly due to brain lesions such as (but not limited to) head injury, stroke, brain breeding and cerebral infection.
• Patients with sub-stupor or stupor.
• One or more seizures without a clear and resolved etiology. However, if the patient has had one or more seizures in the past with an identifiable etiology, and that etiology has been resolved, the patient may be entered.
• Patients who have a history of DSM-IV-TR substance (except caffeine and nicotine) abuse within the past 30 days or substance dependence within the past 6 months before informed consent. Or patients who have a history of using illegal drug.
• Patients whose agitation is caused by substance abuse or neurologic conditions, in the opinion of the investigator or sub-investigator(s).
• Patients who have a diagnosis of Parkinson's disease or dementia.
• Patients who are actively suicidal (at high risk for suicide attempt) in the opinion of the investigator or sub-investigator(s).
• Patients with inadequately controlled diabetes, or patients whose treatment for diabetes have been changed within 4 weeks before the first IM injection of the investigational product. The investigator's discretion will supersede even if the patients do not meet the above criteria for concurrent diabetes.
• Patients who have received haloperidol decanoate fluphenazine decanoate, or fluphenazine enanthate within 8 weeks before the first IM injection of investigational product.
• Patients who have received risperidone long-acting injection within 12 weeks before the first IM injection of investigational product.
• Patients who have a history of receiving injectable depot antipsychotics other than haloperidol decanoate, fluphenazine decanoate, fluphenazine enanthate and risperidone long-acting injection.
• Patients who have received antipsychotics or other prohibited concomitant medicines within 2 hours before the first IM injection of investigational product.
• Patients who have received benzodiazepines within 4 hours before the first IM injection of investigational product.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 64 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eli Lilly and Company Industry

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY(1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM-5PM Eastern time(UTC/GMT-5hours, EST) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00970281

Study ID Number: 13333

ClinicalTrials.gov Identifier: NCT00970281

Health Authority: Japan: Ministry of Health, Labor and Welfare