A Study of Olanzapine in Patients With Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00970281
First received: September 1, 2009
Last updated: March 6, 2012
Last verified: March 2012
  Purpose

The primary objectives of the study is to confirm if the efficacy of intramuscular injection (IM) olanzapine 10 milligrams (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.


Condition Intervention Phase
Schizophrenia
Drug: Rapid-Acting Intramuscular Olanzapine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) Total Score up to 2 Hours After the First Intramuscular (IM) Injection [ Time Frame: Baseline, up to 2 hours after first IM injection ] [ Designated as safety issue: No ]
    Measures excitability and consists of the following 5 items from the PANSS: Excitement, Hostility, Tension, Uncooperativeness, and Poor Impulse Control. Each item is rated on a scale from 1 (absent) to 7 (extreme). The sum of the 5 items is defined as the PANSS-EC total score which ranges from 5 to 35.


Secondary Outcome Measures:
  • Change From Baseline in PANSS-EC Total Score up to 90 Minutes After the First Intramuscular (IM) Injection [ Time Frame: Baseline, 15 minutes, 30 minutes, 60 minutes, and 90 minutes after the first injection ] [ Designated as safety issue: No ]
    Measures excitability and consists of the following 5 items from the PANSS: Excitement, Hostility, Tension, Uncooperativeness, and Poor Impulse Control. Each item is rated on a scale from 1 (absent) to 7 (extreme). The sum of the 5 items is defined as the PANSS-EC total score which ranges from 5 to 35.

  • Change From Baseline in the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) Total Score up to 24 Hours After the First Intramuscular (IM) Injection [ Time Frame: Baseline, up to 24 hours after first IM injection ] [ Designated as safety issue: No ]
    Measures excitability and consists of the following 5 items from the PANSS: Excitement, Hostility, Tension, Uncooperativeness, and Poor Impulse Control. Each item is rated on a scale from 1 (absent) to 7 (extreme). The sum of the 5 items is defined as the PANSS-EC total score which ranges from 5 to 35.

  • Percentage of Participants With 40% or Greater Percent Decrease in the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) Total Score up to 2 Hours After the First Intramuscular (IM) Injection [ Time Frame: Up to 2 hours after the first (IM) injection ] [ Designated as safety issue: No ]
    Measures excitability and consists of the following 5 items from the PANSS: Excitement, Hostility, Tension, Uncooperativeness, and Poor Impulse Control. Each item is rated on a scale from 1 (absent) to 7 (extreme). The sum of the 5 items is defined as the PANSS-EC total score which ranges from 5 to 35.

  • Percentage of Participants With Scores of 4 to 7 in the Agitation-Calmness Evaluation Scale (ACES) Score up to 24 Hours After the First Intramuscular (IM) Injection [ Time Frame: up to 24 hours after the first IM injection ] [ Designated as safety issue: Yes ]
    The ACES differentiates agitation, calmness, and sleep-state, using a 9-point scale: 1 (Marked Agitation) to 9 (Unarousable). Scores of 4 (Normal) to 7 (Marked Calmness) were used for this outcome measure.

  • Percentage of Participants With Treatment-Emergent Extrapyramidal Symptoms Based on the Drug Induced Extrapyramidal Symptoms Scale (DIEPSS) Score up to 24 Hours After the First Intramuscular (IM) Injection [ Time Frame: Up to 24 hours after the first IM injection ] [ Designated as safety issue: Yes ]
    Assesses extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms; 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). Total points of 8 items are defined as DIEPSS total (0 to 32 points). Items for assessment of individual symptoms are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Parkinsonism is assessed by total points of items 1 to 5; akathisia, dystonia and dyskinesia are assessed by points given to corresponding items (item 6, item 7, and item 8, respectively).


Enrollment: 91
Study Start Date: September 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 10 mg Olanzapine Drug: Rapid-Acting Intramuscular Olanzapine
Administered by means of intramuscular injection (IM) with the possibility of second 10 milligram (mg) injection 2 to 4 hours after first injection, for a maximum of 2 injections
Other Names:
  • LY170053
  • RAIM
Placebo Comparator: Placebo Drug: Placebo
Administered by means of IM with the possibility of second injection 2 to 4 hours after first injection, for a maximum of 2 injections

  Eligibility

Ages Eligible for Study:   20 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 intramuscular (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 Agitation-Calmness Evaluation Scale (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 milligrams (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 has 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00970281

Locations
Japan
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Aichi, Japan, 470-1168
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Gunma, Japan, 3703603
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Hokkaido, Japan, 0788208
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Kanagawa, Japan, 234-0051
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Kumamoto, Japan, 8660895
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Nara, Japan, 634-8522
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Okinawa, Japan, 9012111
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Osaka, Japan, 593
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Saitama, Japan, 343-0851
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Tokyo, Japan, 120-0005
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Yamaguchi, Japan, 579-6613
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY(1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM-5PM Eastern time(UTC/GMT-5hours, EST) Eli Lilly and Company
  More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00970281     History of Changes
Other Study ID Numbers: 13333, F1D-JE-RACD
Study First Received: September 1, 2009
Results First Received: January 18, 2012
Last Updated: March 6, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Olanzapine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents

ClinicalTrials.gov processed this record on September 18, 2014