The Study of Olanzapine Plus Fluoxetine in Combination for Treatment of Treatment Resistant Depression - Full Text View

Sponsor:	Eli Lilly and Company
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00035321

Purpose

The purposes of this study are to determine:

Whether olanzapine plus fluoxetine in combination will help patients with treatment-resistant major depression.
The safety of olanzapine plus fluoxetine in combination, plus and any side effects that might be associated with the combination.
The effectiveness of olanzapine plus fluoxetine compared to olanzapine and fluoxetine alone.

Condition	Intervention	Phase
Major Depressive Disorder	Drug: Olanzapine Drug: Fluoxetine	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	The Study of Olanzapine Plus Fluoxetine in Combination for Treatment-Resistant Depression Without Psychotic Features

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants Depression Psychotic Disorders

Drug Information available for: Fluoxetine Fluoxetine hydrochloride Olanzapine

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

To assess the efficacy of up to 8 weeks of treatment with OFC versus olanzapine and fluoxetine monotherapies, in patients with recurrent MDD without psychotic features
who meet study criteria for TRD, as measured by last observation carried forward (LOCF) mean change from baseline to endpoint in the MADRS total score
Treatment-resistant depression will be defined as:historic failure to achieve satisfactory response to an antidepressant (other than fluoxetine) during the current MDD episode
when treated with an acceptable antidepressant drug and dose for at least 6 weeks
prospective failure to achieve a satisfactory response to fluoxetine monotherapy during the 8 week study lead-in phase

Secondary Outcome Measures:

To compare the efficacy, safety, and quality of life results of up to 8 weeks of OFC therapy(treatment phase) with fluoxetine and olanzapine monotherapies using the following assessments:
Onset of action as measured by time to achieve and initial response (greater than or equal to 25% reduction from baseline in MADRS total score
Efficacy in the treatment of co-morbid anxiety symptoms as measured by LOCF mean change from baseline to endpoint in Hamilton Psychiatric Rating Scale for Anxiety (HAM-A)total score
Study-defined response and remission rates including time to achieve a full response (defined as greater than or equal to 50% reduction in MADRS total score)
and time to achieve remission (defined as MADRS total score less than or equal to 10 at endpoint)
LOCF mean change from baseline to endpoint in Clinical Global Impression - Severity of Depression score
(CGI-Severity of Depression), individual MADRS questions,and HAM-A item scores
Repeated measures analyses of post-baseline MADRS and HAM-A total scores
The incidence and severity of treatment-emergent adverse events and EPS. The Barnes Akathisia Scale,Simpson-Angus Scale, and the Abnormal Involuntary Movement Scale (AIMS) will be used to assess EPS
The Brief Psychiatric Rating Scale (BPRS) to evaluate the emergence of psychosis
Changes in vital signs and weight, laboratory analytes, and electrocardiograms (ECG)),Quality of life as measured by the LOCF mean change from baseline to endpoint on the Sheehan Disability Scale (SDS) score and the Short Form 36 Health Survey
Additional secondary objectives are to assess the efficacy, safety, and quality of life results of up to 8 additional weeks of open-label OFC therapy (after the treatment phase)using the following measures:
LOCF mean change from baseline to endpoint in MADRS, HAM-A, and CGI-Severity of Depression scores and study-defined rates of response and remission
Safety as measured by the incidence and severity of treatment-emergent adverse events, and EPS using the Barnes Akithisia Scale, Simpson Angus Scale and the AIM
The BPRS to examine the emergence of psychosis
Changes in vital signs and weight, laboratory analytes, and ECG

Estimated Enrollment:	600
Study Start Date:	April 2002
Estimated Study Completion Date:	July 2005

Eligibility

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

Criteria

Inclusion Criteria:

Male or female patients, 18 - 65 years of age.
Each patient must have a level of understanding sufficient to perform all tests and examinations required by the protocol, and must be considered reliable according to the investigator's clinical judgement
Patients must fulfill the criteria for recurrent MDD without psychotic features as defined by the DSM-IV, based on clinical assessment and confirmed by Structured Clinical Interview for DSM-IV Axis I Disorders - Clinical Version (SCID-I) plus the Major Depressive Disorder Specifiers included in the Research Version of the SCID-I. This includes at least one of the following diagnoses: 296.31, 296.32, and 296.33
Female patients of childbearing potential must be using a medically accepted means of contraception throughout the course of the study. Use of any oral or injectable contraception must be initiated prior to visit 2
Failure to achieve satisfactory antidepressant response to an adequate trial of an antidepressant (except fluoxetine), for at least 6 weeks at an acceptable dose or greater, occurring within the current episode of MDD

Exclusion Criteria:

Treatment with a drug within the last 30 days that has not received regulatory approval at the time of study entry
Exposure to OFC in a Lilly-sponsored clinical trial investigating OFC, and any patients historically failing to respond to olanzapine and fluoxetine in combination under any circumstance
Persons who have previously entered any Lilly-sponsored study which was investigating olanzapine
Female patients who are either pregnant or nursing
Serious, unstable illnesses for which death is anticipated within 1 year of intensive care unit hospitalization for the disease is anticipated within 6 months. This includes hepatic (specifically any degree of jaundice), renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic diseases (specifically current agranulocytosis with an absolute neutrophil count < 500 mm_3)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00035321

Show 33 Study Locations

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

More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Thase ME, Corya SA, Osuntokun O, Case M, Henley DB, Sanger TM, Watson SB, Dube S. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry. 2007 Feb;68(2):224-36.

Study ID Numbers:	6272, H6P-MC-HDAO
Study First Received:	May 2, 2002
Last Updated:	July 21, 2006
ClinicalTrials.gov Identifier:	NCT00035321 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Olanzapine
Psychotropic Drugs
Antiemetics
Depressive Disorder, Major
Mental Disorders
Therapeutic Uses
Antidepressive Agents, Second-Generation
Antidepressive Agents
Depression
Tranquilizing Agents

Gastrointestinal Agents
Central Nervous System Depressants
Depressive Disorder
Antipsychotic Agents
Serotonin Uptake Inhibitors
Pharmacologic Actions
Behavioral Symptoms
Fluoxetine
Serotonin Agents
Autonomic Agents
Mood Disorders
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 25, 2009