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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00190892




Registration number
NCT00190892
Ethics application status
Date submitted
12/09/2005
Date registered
19/09/2005
Date last updated
26/01/2007

Titles & IDs
Public title
Olanzapine Plus Carbamazepine in the Treatment of Bipolar I Mania
Scientific title
Olanzapine Plus Carbamazepine Versus Carbamazepine Alone in the Treatment of Manic or Mixed Episodes Associated With Bipolar I Disorder
Secondary ID [1] 0 0
F1D-MC-HGKR
Secondary ID [2] 0 0
7031
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bipolar Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Other mental health disorders
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - olanzapine
Treatment: Drugs - carbamazepine

Treatment: Drugs: olanzapine


Treatment: Drugs: carbamazepine
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Secondary outcome [2] 0 0
Using the following assessments:
Timepoint [2] 0 0
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Secondary outcome [5] 0 0
reductions from baseline to the endpoint of the 6-week, double-blind treatment phase on the Montgomery-Asberg Depression Rating Scale (MADRS) total score
Timepoint [5] 0 0
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Secondary outcome [9] 0 0
symptoms of depression
Timepoint [9] 0 0
Secondary outcome [10] 0 0
longitudinal effects from baseline across visits of the double-blind treatment phase by comparing changes in YMRS total scores
Timepoint [10] 0 0
Secondary outcome [11] 0 0
changes in vital signs and weight, laboratory analytes, and electrocardiograms (ECGs), and the incidence and severity of TEAEs and extrapyramidal symptoms (EPS)
Timepoint [11] 0 0
Secondary outcome [12] 0 0
using the Barnes Akathisia Scale, Simpson-Angus Scale and the AIMS.
Timepoint [12] 0 0
Secondary outcome [13] 0 0
the effect of carbamazepine on the plasma concentration of olanzapine via comparison to historic oral steady-state olanzapine concentrations
Timepoint [13] 0 0
Secondary outcome [14] 0 0
the effect of olanzapine on the plasma concentrations of carbamazepine via a descriptive comparison of the two treatment groups
Timepoint [14] 0 0
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
Secondary outcome [16] 0 0
using the following measures:
Timepoint [16] 0 0
Secondary outcome [17] 0 0
YMRS total score change from the baseline (Visit 7) to the endpoint of the open-label treatment phase.
Timepoint [17] 0 0
Secondary outcome [18] 0 0
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:
Timepoint [18] 0 0
Secondary outcome [19] 0 0
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
Timepoint [19] 0 0
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
Secondary outcome [21] 0 0
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
Timepoint [21] 0 0
Secondary outcome [22] 0 0
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
Timepoint [22] 0 0
Secondary outcome [23] 0 0
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)
Timepoint [23] 0 0

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
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
Recruitment hospital [2] 0 0
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
Recruitment hospital [3] 0 0
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
Recruitment hospital [4] 0 0
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
Recruitment postcode(s) [1] 0 0
- Everton Park
Recruitment postcode(s) [2] 0 0
- Epping
Recruitment postcode(s) [3] 0 0
- Frankston
Recruitment postcode(s) [4] 0 0
- Malvern
Recruitment outside Australia
Country [1] 0 0
Greece
State/province [1] 0 0
Corfu
Country [2] 0 0
Greece
State/province [2] 0 0
Kavala
Country [3] 0 0
Greece
State/province [3] 0 0
Tripoli
Country [4] 0 0
Hungary
State/province [4] 0 0
Budapest
Country [5] 0 0
Hungary
State/province [5] 0 0
Debrecen
Country [6] 0 0
Hungary
State/province [6] 0 0
Gyula
Country [7] 0 0
Hungary
State/province [7] 0 0
Szekesfehervar
Country [8] 0 0
Russian Federation
State/province [8] 0 0
Moscow
Country [9] 0 0
Russian Federation
State/province [9] 0 0
St. Petersburg

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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
Trial website
https://clinicaltrials.gov/ct2/show/NCT00190892
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00190892