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Olanzapine Plus Carbamazepine in the Treatment of Bipolar I Mania

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00190892
First received: September 12, 2005
Last updated: January 24, 2007
Last verified: January 2007
  Purpose

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


Condition Intervention Phase
Bipolar Disorder
Drug: olanzapine
Drug: carbamazepine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Olanzapine Plus Carbamazepine Versus Carbamazepine Alone in the Treatment of Manic or Mixed Episodes Associated With Bipolar I Disorder

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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.
  • 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 Outcome Measures:
  • 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
  • Using the following assessments:
  • 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.
  • 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
  • reductions from baseline to the endpoint of the 6-week, double-blind treatment phase on the Montgomery-Asberg Depression Rating Scale (MADRS) total score
  • 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
  • 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
  • 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
  • symptoms of depression
  • longitudinal effects from baseline across visits of the double-blind treatment phase by comparing changes in YMRS total scores
  • changes in vital signs and weight, laboratory analytes, and electrocardiograms (ECGs), and the incidence and severity of TEAEs and extrapyramidal symptoms (EPS)
  • using the Barnes Akathisia Scale, Simpson-Angus Scale and the AIMS.
  • the effect of carbamazepine on the plasma concentration of olanzapine via comparison to historic oral steady-state olanzapine concentrations
  • the effect of olanzapine on the plasma concentrations of carbamazepine via a descriptive comparison of the two treatment groups
  • 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
  • using the following measures:
  • YMRS total score change from the baseline (Visit 7) to the endpoint of the open-label treatment phase.
  • 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:
  • 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
  • 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
  • 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
  • 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
  • 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)

Estimated Enrollment: 120
Study Start Date: September 2004
Estimated Study Completion Date: June 2006
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00190892

Locations
Australia, Queensland
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
Australia, Victoria
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
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, Australia
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, 491 00
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, 654 03
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, Greece, 221 00
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, Hungary
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, Russian Federation
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 to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00190892     History of Changes
Other Study ID Numbers: 7031, F1D-MC-HGKR
Study First Received: September 12, 2005
Last Updated: January 24, 2007
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bipolar Disorder
Disease
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Pathologic Processes
Carbamazepine
Olanzapine
Analgesics
Analgesics, Non-Narcotic
Anticonvulsants
Antiemetics
Antimanic Agents
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 27, 2014