Efficacy and Safety of Olanzapine in the Extended Treatment for 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:	NCT00266630

Purpose

The efficacy and safety of the extended treatment to patients with most recent episode manic or mixed who completed previous double blind study (F1D-JE-BMAC [Study BMAC]) will be examined.

Condition	Intervention	Phase
Manic or Mixed Episode Associated With Bipolar I Disorder	Drug: olanzapine Drug: lithium Drug: valproate Drug: carbamazepine	Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Efficacy and Safety of Olanzapine in the Extended Treatment for Manic or Mixed Episode of Bipolar I Disorder

Resource links provided by NLM:

Drug Information available for: Divalproex sodium Valproic acid Olanzapine Carbamazepine Lithium carbonate Lithium citrate Valproate Sodium

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Scores - Olanzapine Monotherapy Arm Only [ Time Frame: baseline through 18 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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.
Number of Participants With Response of Manic Symptoms - Olanzapine Monotherapy Arm Only [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: No ]
Defined by a 50% or more reduction in YMRS total score from baseline in Study BMAC to endpoint. 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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.
Number of Participants With Remission of Mania - Olanzapine Monotherapy Arm Only [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: No ]
Remission of Mania was defined as a YMRS total score of less than or equal to 12 at endpoint. 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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.
Number of Participants With Relapse of Manic Symptoms - Olanzapine Monotherapy Arm Only [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: No ]
Patients achieved remission in Study BMAC (defined as YMRS total score <=12 and HAMD-17 total score <=7) and obtained YMRS total score of >=15 at any time during Study BMEX. 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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.

Secondary Outcome Measures:

Change From Baseline to Endpoint on the YMRS Total Score - Olanzapine + Mood Stabilizer Only [ Time Frame: baseline through 18 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.
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data [ Time Frame: baseline, Weeks 1, 2, 4, 6, 10, 14, 18 ] [ Designated as safety issue: No ]
Measures severity of the patient's overall severity of bipolar symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Number of Participants Who Experienced Switch to Symptomatic Depression as Measured by the Hamilton Depression Scale - 17 Item Version (HAMD-17) [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: No ]
Incidence of depressive symptoms was defined as a score of equal to or more than 13 points on the HAMD-17. The 17-item HAMD measures depression severity. Each item was evaluated and scored a 3-point scale (e.g. absent, mild, marked) or a 5-point scale (e.g. absent, mild, moderate, severe, very severe). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Number of Participants With Relapse of Depressive Symptoms [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: No ]
Assessed were participants meeting remission criteria for bipolar disorder in Study BMAC and have a HAMD-17 total score greater than or equal to 13 at any time. The 17-item HAMD measures depression severity. Each item was evaluated and scored using a 3-point scale (e.g. absent, mild, marked) or a 5-point scale (e.g. absent, mild, moderate, severe, very severe). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Number of Participants Who Experienced Remission of Bipolar Disorder [ Time Frame: Week 18 ] [ Designated as safety issue: No ]
Participants who had equal to or less than 12 points in YMRS total score and equal to or less than 7 points in HAMD-17 total score at 18 weeks. YMRS: 11-item scale, measures the severity of manic episodes. 4 items are rated from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total: 0 to 60. The 17-item HAMD measures depression severity. Each item was evaluated and scored using a 3-point scale or a 5-point scale. HAMD-17 total score: 0 (normal) to 52 (severe).
Positive and Negative Syndrome Scale Positive Scores - Visit Data [ Time Frame: baseline, Weeks 1, 2, 4, 6, 10, 14, 18 ] [ Designated as safety issue: No ]
Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale. 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 the analysis, the score was converted to 0 to 6 for each item range; hence, the total score ranges from 0 to 42.
Number of Participants Who Switched to Syndromic Depression [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: No ]
As defined as a shift from a Manic Episode at baseline to a Major Depressive Episode, at any post baseline visit, based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision.
Maximum Change From Baseline to Endpoint on the Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) - Total Score [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
A scale used to assess the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). The items for the assessment of individual symptoms are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Parkinsonism is assessed by the total points of items 1 to 5; akathisia, dystonia and dyskinesia are assessed by the points given to the corresponding items.
Number of Participants With Treatment-Emergent Parkinsonism Based on DIEPSS Scores [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
DIEPSS assesses the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). Parkinsonism is assessed by the total points of items 1 to 5 (total score of 0 to 20). Treatment-emergent parkinsonism was defined as a score of equal or greater than 3 on 1 item, equal or greater than 2 on 2 items, or an increase of equal or greater than 3 from baseline on the parkinsonism total.
Number of Participants With Treatment-Emergent Akathisia Based on DIEPSS Scores [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
DIEPSS assesses the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). The items are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Treatment-emergent akathisia was defined as a score of equal or more than 2 or an increase of equal or more than 2 points from baseline on the akathisia item (total score possible 0 to 4 points).
Number of Participants With Treatment-Emergent Dystonia Based on DIEPSS Scores [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
DIEPSS assesses the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). The items are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Treatment-emergent dystonia was defined as a score equal or more than 2 or an increase of equal or more than 2 points from baseline on the dystonia item (total score possible 0 to 4 points).
Number of Participants With Treatment-Emergent Dyskenisia Based on DIEPSS Scores [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
DIEPSS assesses the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). The items are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Treatment-emergent dyskenisia was defined as a score of equal or more than 2 or an increase of equal to or more than 2 points from baseline on the dyskenisia item (total score possible 0 to 4 points).
Number of Participants With Potentially Clinically Significant Changes in Laboratory Analytes [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
Triglycerides: high limit equal to or more than 500 milligram/deciliter (mg/dL); Glucose (non-fasting): low limit 2.4975 mmol/liter (L); high limit 13.875 mmol/L; Glucose (fasting): low limit 2.4975 mmol/L; high limit 6.993 mmol/L.
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
Low systolic blood pressure (SBP): <=90 millimeter mercury (mmHg) and decrease of >=20 mmHg; High SBP: >=180 mmHg and increase of >=20 mmHg; Low diastolic blood pressure (DBP): <=50 mmHg and decrease of >=15 mmHg; High DBP: >=105 mmHg and increase of >=15 mmHg; Low pulse: <50 beats per minute (bpm) and decrease of >=15 bpm; High pulse: >120 bpm and an increase of >=15 bpm; Low weight: decrease of >=7%; High weight: increase of >=7%;
Number of Participants With Potentially Clinically Significant Changes in Electrocardiograms - High Fridericia Corrected QT Interval (QTcF) [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
High QTcF: more than or equal to 450 milliseconds (msec) for males; more than or equal to 470 milliseconds (msec) for females
Number of Participants With Treatment-emergent Abnormal, High, or Low Laboratory Values [ Time Frame: baseline through 18 weeks ] [ Designated as safety issue: Yes ]
High density lipoprotein: males low 40 milligram/deciliter (mg/dL), high 80 mg/dL; females low 40 mg/dL, high 90 mg/dL. Low density lipoprotein (LDL): males and females low 70 mg/dL, high 139 mg/dL. Hemoglobin A1C (HBA1C): males and females low 4.3%, high 5.8%.

Enrollment:	139
Study Start Date:	November 2005
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Olanzapine Monotherapy Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Drug: olanzapine oral, daily Other Names: LY170053 Zyprexa
Experimental: Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.	Drug: olanzapine oral, daily Other Names: LY170053 Zyprexa Drug: lithium Dose adjusted according to local package insert Drug: valproate Dose adjusted according to local package insert Drug: carbamazepine Dose adjusted according to local package insert

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00266630

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.
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, 292-0061
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, 812-8582
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, 371-8511
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, 005-0004
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.
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.
Okayama, Japan, 710-0055
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, 900-0005
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.
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, 151-0053

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 9 AM - 5 PM Eastern time (UTC/GMT-5 hours, EST)

Eli Lilly and Company

Ages Eligible for Study:	20 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00266630 History of Changes
Other Study ID Numbers:	9637, F1D-JE-BMEX
Study First Received:	December 15, 2005
Results First Received:	May 26, 2010
Last Updated:	December 10, 2010
Health Authority:	Japan: Ministry of Health, Labor and Welfare