Olanzapine Plus Carbamazepine in the Treatment of Bipolar I Mania

Bipolar Disorder Clinical Trial

Official title:

Olanzapine Plus Carbamazepine Versus Carbamazepine Alone in the Treatment of Manic or Mixed Episodes Associated With Bipolar I Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00190892
• Other study ID #: 7031
• Secondary ID: F1D-MC-HGKR
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2005
• Last updated: January 24, 2007
• Start date: September 2004
• Est. completion date: June 2006

Study information

• Verified date: January 2007
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This trial will assess any efficacious benefit and any safety issues associated with the concomitant use of olanzapine and carbamazepine for the treatment of patients with bipolar I disorder, manic or mixed episodes

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Have a diagnosis of bipolar disorder and currently meet DSM-IV-TR criteria for a manic or mixed episode

2. Female patients must test negative on a serum pregnancy test at the time of enrollment and agree to use medically accepted contraception throughout the study.

3. Have YMRS score > or = 20 at both the screening (Visit 1) and randomization (Visit 2) visits.

Exclusion Criteria:

1. Have participated (been randomized) in a clinical trial of another investigational drug (including olanzapine or carbamazepine) within 30 days prior to Visit 1

2. Have a history of agranulocytosis (absolute neutrophil count< 500/uL) during the patient's lifetime

3. Have acute, serious or unstable medical conditions, including (but not limited to) inadequately controlled diabetes (HgbA1c>8%); severe hypertriglyceridemia (fasting triglycerides > or = 500 mg/dl;hepatic insufficiency (specifically any degree of jaundice); recent cerebrovascular accidents; uncontrolled seizure disorders; serious acute systemic infection or immunologic disease: unstable cardiovascular disorders (including ischemic heart disease); or renal, gastroenterologic, respiratory, endocrinologic, neurologic, or hematologic diseases (specifically current absolute neutrophil count , <1500/uL)

4. Have a substance dependence (except nicotine or caffeine), based on DSM-IV-TR criteria, within the 30 days prior to study entry.

5. Require concomitant treatment with any other medication with primarily central nervous system (CNS) activity, other than those allowed in the protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• olanzapine

• carbamazepine

Locations

Country	Name	City	State
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Epping	Victoria
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Everton Park	Queensland
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Frankston	Victoria
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Malvern	Victoria
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Corfu
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Kavala
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Tripoli
Hungary	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Budapest
Hungary	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Debrecen
Hungary	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Gyula
Hungary	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Szekesfehervar
Russian Federation	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Moscow
Russian Federation	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	St. Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Australia,  Greece,  Hungary,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the superiority of olanzapine plus carbamazepine versus placebo plus carbamazepine in improving overall manic symptomatology in patients with mania associated with bipolar I disorder.
Primary	Improvement is measured by a reduction in the total score of the Young Mania Rating Scale (YMRS) from baseline to endpoint during the 6-week, double-blind treatment phase.
Secondary	To compare the efficacy and safety of up to 6 weeks of double-blind, concomitant use of olanzapine plus carbamazepine to the concomitant use of placebo plus carbamazepine
Secondary	Using the following assessments:
Secondary	rate of response and time to response over 6 weeks of the double-blind treatment phase, with response defined as a reduction of 50% or more in the YMRS total score from baseline to endpoint.
Secondary	rate of remission and time to remission of mania over 6 weeks of the double-blind treatment phase, with remission defined as a score less than or equal to 12 on the YMRS total score at endpoint
Secondary	reductions from baseline to the endpoint of the 6-week, double-blind treatment phase on the Montgomery-Asberg Depression Rating Scale (MADRS) total score
Secondary	reductions from baseline to the endpoint of the 6-week, double-blind treatment phase on the Clinical Global Impressions-Bipolar Version Severity of Illness Scale (CGI-BP)score
Secondary	rate of switch to depression and time to switch to depression, with switch to depression defined as a baseline MADRS total score less than or equal to 12 followed by
Secondary	either a post baseline MADRS total score greater than or equal to 16 over the 6 weeks of the double-blind treatment phase OR, hospitalization due to deterioration in clinical
Secondary	symptoms of depression
Secondary	longitudinal effects from baseline across visits of the double-blind treatment phase by comparing changes in YMRS total scores
Secondary	changes in vital signs and weight, laboratory analytes, and electrocardiograms (ECGs), and the incidence and severity of TEAEs and extrapyramidal symptoms (EPS)
Secondary	using the Barnes Akathisia Scale, Simpson-Angus Scale and the AIMS.
Secondary	the effect of carbamazepine on the plasma concentration of olanzapine via comparison to historic oral steady-state olanzapine concentrations
Secondary	the effect of olanzapine on the plasma concentrations of carbamazepine via a descriptive comparison of the two treatment groups
Secondary	Additional secondary objectives are to assess the maintenance of treatment effect and safety of up to 20 weeks of open-label olanzapine-plus-carbamazepine treatment
Secondary	using the following measures:
Secondary	YMRS total score change from the baseline (Visit 7) to the endpoint of the open-label treatment phase.
Secondary	rate of relapse to mania during the open-label treatment phase. Relapse to mania (patients who relapse to a bipolar I mania or mixed episode) is defined by the following:
Secondary	patient reaches remission of mania (as defined by a YMRS score less than or equal to 12) by the endpoint of the double-blind treatment phase
Secondary	patient obtains a YMRS score greater than or equal to 15 at any time during the open label treatment phase AND/OR becomes hospitalized due to deterioration in clinical symptoms of mania
Secondary	rate of switch to depression during open-label treatment phase, with switch to depression defined as a baseline MADRS total score less than or equal to 12 followed by
Secondary	either a postbaseline MADRS total score greater than or equal to 16 over the 20 weeks of the open-label treatment phase hospitalization due to deterioration in clinical symptoms of depression
Secondary	changes in vital signs and weight, laboratory analytes, and ECGs, and the incidence and severity of TEAEs and EPS using the Barnes Akathisia Scale, Simpson-Angus Scale, and the Abnormal Involuntary Movement Scale (AIMS)