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Trial of Olanzapine in Patients With Manic or Mixed Episode of Bipolar I Disorder

Phase 3
Completed
Conditions
Bipolar Disorder
Interventions
Registration Number
NCT00129220
Lead Sponsor
Eli Lilly and Company
Brief Summary

The purpose of this study is to confirm the efficacy of olanzapine in the treatment of manic or mixed symptoms associated with bipolar I disorder.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
224
Inclusion Criteria
  • Meet the criteria for manic or mixed episodes according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) and have a diagnosis of "294.4x Bipolar I Disorder, Most Recent Episode Manic" or "296.6x Bipolar I Disorder, Most Recent Episode Mixed".
  • Have a total score on the Young Mania Rating Scale (YMRS) of at least 20 at Visit 1 and Visit 2.
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Exclusion Criteria
  • Have received an antidepressant or a psychostimulant within 5 days prior to Visit 1.
  • The duration of the current episode is more than 90 days at Visit 1.
  • Have a history or a diagnosis of diabetes mellitus.
  • Have received any psychotropic medication within 2 days prior to Visit 2 (except for benzodiazepines).
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placeboplaceboplacebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Haloperidolhaloperidolhaloperidol: 2.5 to 10 mg per day for 6 weeks
Olanzapineolanzapineolanzapine: 5 to 20 mg per day for 6 weeks
Primary Outcome Measures
NameTimeMethod
Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total ScoreBaseline, 3 weeks

The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS)Baseline, 6 weeks

The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.

Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol)6 weeks

Remission of bipolar disorder was defined as completing the 6-week period with meeting the criteria for Young Mania Rating Scale (YMRS) total score of 12 or less and 17-Item Hamilton Depression Rating Scale (HAMD-17) total scores of 7 or less at Week 6. YMRS is an 11-item scale measuring severity of manic episodes; total score ranges = 0 (normal) to 60 (severe). The 17-item HAMD measures depression severity; total score ranges = 0 (normal) to 52 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100.

Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of IllnessBaseline, 6 weeks

A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of overall mood symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania SubscaleBaseline, 3 weeks, 6 weeks

A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of manic symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

Response Rate of Manic Symptoms at 3 Weeks and 6 WeeksBaseline, 3 weeks, 6 weeks

Participants who had 50 percent or more decrease from the baseline in YMRS total scores were defined as a responder. The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. Response Rate (percent) = number of patients meeting response criterion for manic symptom divided by number of patients in treatment arm, multiplied by 100.

Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks3 weeks, 6 weeks

Participants who had a YMRS total score of 12 or less were considered to be in remission of manic symptoms. YMRS is an 11-item scale that measures severity of manic episodes; total score ranges from 0 (normal) to 60 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100.

Percentage of Participants Who Switched to Symptomatic Depression3 weeks, 6 weeks

Switch to symptomatic depression was defined as HAMD-17 total score ≥13 at any time in the participants with HAMD-17 total scores ≤7 at baseline. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).

Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS)Baseline, 3 weeks, 6 weeks

Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total Positive Subscale scores range from 7 to 49. For this study, the score was converted to 0 to 6 for each item range; hence, the total positive subscale score ranges from 0 to 42.

Percentage of Participants Who Switched to Syndromic Depression3 weeks, 6 weeks

Switch to syndromic depression was operationally defined by meeting both of the following criteria: At baseline, the symptoms did not meet the criteria for a mixed episode based on the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). The critiera were met for a Major Depressive Episode (MDE), at any point after randomization, based on DSM-IV-TR. Rather than the 2-week period required for an MDE in the DSM-IV-TR, the patient had to meet the criteria of an MDE for at least 7 consecutive days (during Weeks 1 through 6).

Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total ScoreBaseline to 6 weeks

Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the sum of the 8 item scores, for a total range of 0 (normal) to 32 (severe).

Trial Locations

Locations (1)

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.

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Tokyo, Japan

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