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

Eli Lilly and Company224 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

224

Conditions

Bipolar Disorder

Interventions

olanzapineDRUG

5-20 mg, oral, once daily (evening), for 6 weeks

haloperidolDRUG

2.5-10 mg, oral, twice daily (morning and evening), for 6 weeks.

placeboDRUG

placebo, oral tablets, twice daily (morning and evening), for 3 weeks

Eligibility

Sex: ALLMin age: 20 YearsMax age: 65 Years

Medical Language ↔ Plain English

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. 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).

Locations (16)

Outcomes

Primary Outcomes

Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score

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.

Time frame: Baseline, 3 weeks

Secondary Outcomes

Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS)

Time frame: Baseline, 6 weeks

Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol)

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.

Time frame: 6 weeks

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

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).

Time frame: Baseline, 6 weeks

Data from ClinicalTrials.gov

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Aichi, Japan

Akita, Japan

Chiba, Japan

Fukuoka, Japan

Gunma, Japan

Hokkaido, Japan

Hyōgo, Japan

Kanagawa, Japan

Kumamoto, Japan

Nagano, Japan

...and 6 more locations

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

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).

Time frame: Baseline, 3 weeks, 6 weeks

Response Rate of Manic Symptoms at 3 Weeks and 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.

Time frame: Baseline, 3 weeks, 6 weeks

Remission Rate of Manic Symptoms at 3 Weeks and 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.

Time frame: 3 weeks, 6 weeks

Percentage of Participants Who Switched to Symptomatic Depression

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).

Time frame: 3 weeks, 6 weeks

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

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.

Time frame: Baseline, 3 weeks, 6 weeks

Percentage of Participants Who Switched to Syndromic Depression

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).

Time frame: 3 weeks, 6 weeks

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

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).

Time frame: Baseline to 6 weeks