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

• ClinicalTrials.gov Identifier: NCT00129220
• Recruitment Status: Completed
• First Posted: August 11, 2005
• Results First Posted: February 15, 2010
• Last Update Posted: December 28, 2010
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Bipolar Disorder	Drug: olanzapine; Drug: haloperidol; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Placebo- and Haloperidol-Controlled Double-Blind Trial of Olanzapine in Patients With Manic or Mixed Episode of Bipolar I Disorder
• Study Start Date: July 2005
• Actual Primary Completion Date: January 2009
• Actual Study Completion Date: January 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Olanzapine; olanzapine: 5 to 20 mg per day for 6 weeks	Drug: olanzapine; 5-20 mg, oral, once daily (evening), for 6 weeks; Other Names: LY170053; Zyprexa
Active Comparator: Haloperidol; haloperidol: 2.5 to 10 mg per day for 6 weeks	Drug: haloperidol; 2.5-10 mg, oral, twice daily (morning and evening), for 6 weeks.
Placebo Comparator: Placebo; placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks	Drug: placebo; placebo, oral tablets, twice daily (morning and evening), for 3 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score [ Time Frame: Baseline, 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 :

1. Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) [ Time Frame: 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.
2. Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol) [ Time Frame: 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.
3. Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness [ Time Frame: Baseline, 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).
4. Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale [ Time Frame: Baseline, 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).
5. Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks [ Time Frame: Baseline, 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.
6. Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks [ Time Frame: 3 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.
7. Percentage of Participants Who Switched to Symptomatic Depression [ Time Frame: 3 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).
8. Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 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.
9. Percentage of Participants Who Switched to Syndromic Depression [ Time Frame: 3 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).
10. Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score [ Time Frame: Baseline 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).

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

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

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Akita, Japan, 010-1654

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Chiba, Japan, 283-0062

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Fukuoka, Japan, 807-8555

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Gunma, Japan, 370-2455

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Hokkaido, Japan, 004-0841

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Hyogo, Japan, 663-8501

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Kanagawa, Japan, 236-0037

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Kumamoto, Japan, 861-0002

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Nagano, Japan, 384-8540

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Okayama, Japan, 700-8558

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Okinawa, Japan, 904-2222

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Osaka, Japan, 561-0803

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Saga, Japan, 842-0192

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Saitama, Japan, 343-0032

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, 160-0023

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Monday-Friday 9am-5pm Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Katagiri H, Takita Y, Tohen M, Higuchi T, Kanba S, Takahashi M. Efficacy and safety of olanzapine in the treatment of Japanese patients with bipolar I disorder in a current manic or mixed episode: a randomized, double-blind, placebo- and haloperidol-controlled study. J Affect Disord. 2012 Feb;136(3):476-84. doi: 10.1016/j.jad.2011.10.045. Epub 2011 Nov 30.

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00129220
• Other Study ID Numbers: 9636; F1D-JE-BMAC ( Other Identifier: Eli Lilly and Company )
• First Posted: August 11, 2005
• Results First Posted: February 15, 2010
• Last Update Posted: December 28, 2010
• Last Verified: December 2010

Keywords provided by Eli Lilly and Company:

Manic or mixed episode associated with bipolar I disorder

Additional relevant MeSH terms:

Disease; Bipolar Disorder; Pathologic Processes; Bipolar and Related Disorders; Mental Disorders; Haloperidol; Olanzapine; Haloperidol decanoate; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Dopamine Antagonists; Dopamine Agents; Anti-Dyskinesia Agents