The Study of Olanzapine Plus Fluoxetine in Combination for Treatment of Treatment Resistant Depression

Condition(s) targeted: Major Depressive Disorder

Intervention: Olanzapine (Drug); Fluoxetine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Eli Lilly and Company

Official(s) and/or principal investigator(s):
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), Study Director, Affiliation: Eli Lilly and Company

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.

Official title: The Study of Olanzapine Plus Fluoxetine in Combination for Treatment-Resistant Depression Without Psychotic Features

Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

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:

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

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician., St. John, Canada

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Torrance, California, United States

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Oceanside, California, United States

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For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician., New London, Connecticut, United States

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician., St. Petersburg, Florida, United States

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For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Richmond, Virginia, United States

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Waukesha, Wisconsin, United States

Starting date: April 2002
Ending date: July 2005
Last updated: July 21, 2006