Trial of Olanzapine in Patients With Manic or Mixed Episode of Bipolar I Disorder - Full Text View

Sponsor:	Eli Lilly and Company
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00129220

Purpose

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	Intervention	Phase
Bipolar Disorder	Drug: olanzapine Drug: haloperidol Drug: placebo	Phase III

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:	Placebo- and Haloperidol-Controlled Double-Blind Trial of Olanzapine in Patients With Manic or Mixed Episode of Bipolar I Disorder

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Haloperidol Haloperidol decanoate Haloperidol lactate Olanzapine

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score [ Time Frame: Baseline, 3 weeks ] [ Designated as safety issue: No ]
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:

Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
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) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
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 Illness [ Time Frame: Baseline, 6 weeks ] [ Designated as safety issue: No ]
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 Subscale [ Time Frame: Baseline, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
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 Weeks [ Time Frame: Baseline, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
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 Weeks [ Time Frame: 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
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 Depression [ Time Frame: 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
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) [ Time Frame: Baseline, 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
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 Depression [ Time Frame: 3 weeks, 6 weeks ] [ Designated as safety issue: No ]
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 Score [ Time Frame: Baseline to 6 weeks ] [ Designated as safety issue: Yes ]
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).

Enrollment:	224
Study Start Date:	July 2005
Study Completion Date:	January 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	20 Years to 65 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00129220

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.
Akita, Japan, 010-1654
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.
Chiba, Japan, 283-0062
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.
Fukuoka, Japan, 807-8555
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, 370-2455
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, 004-0841
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.
Hyogo, Japan, 663-8501
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, 236-0037
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, 861-0002
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.
Nagano, Japan, 384-8540
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.
Okayama, Japan, 700-8558
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, 904-2222
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, 561-0803
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.
Saga, Japan, 842-0192
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, 343-0032
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

No publications provided

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00129220 History of Changes
Other Study ID Numbers:	9636, F1D-JE-BMAC
Study First Received:	August 8, 2005
Results First Received:	January 21, 2010
Last Updated:	December 10, 2010
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Eli Lilly and Company:

Manic or mixed episode associated with bipolar I disorder

Additional relevant MeSH terms:

Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Haloperidol
Olanzapine
Haloperidol decanoate
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
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents

ClinicalTrials.gov processed this record on February 09, 2012