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

Primary Purpose

Major Depressive Disorder

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Olanzapine

Fluoxetine

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Outcomes

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

Full Information

NCT ID

NCT00035321

First Posted

May 2, 2002

Last Updated

July 21, 2006

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00035321

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2006

Overall Recruitment Status

Completed

Study Start Date

April 2002 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

July 2005 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Eli Lilly and Company

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Double

Allocation

Randomized

Enrollment

600 (false)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Olanzapine

Intervention Type

Drug

Intervention Name(s)

Fluoxetine

Primary Outcome Measure Information:

Title

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

Title

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

Title

Treatment-resistant depression will be defined as:historic failure to achieve satisfactory response to an antidepressant (other than fluoxetine) during the current MDD episode

Title

when treated with an acceptable antidepressant drug and dose for at least 6 weeks

Title

prospective failure to achieve a satisfactory response to fluoxetine monotherapy during the 8 week study lead-in phase

Secondary Outcome Measure Information:

Title

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:

Title

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

Title

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

Title

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)

Title

and time to achieve remission (defined as MADRS total score less than or equal to 10 at endpoint)

Title

LOCF mean change from baseline to endpoint in Clinical Global Impression - Severity of Depression score

Title

(CGI-Severity of Depression), individual MADRS questions,and HAM-A item scores

Title

Repeated measures analyses of post-baseline MADRS and HAM-A total scores

Title

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

Title

The Brief Psychiatric Rating Scale (BPRS) to evaluate the emergence of psychosis

Title

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

Title

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

Title

The BPRS to examine the emergence of psychosis

Title

Changes in vital signs and weight, laboratory analytes, and ECG

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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.

City

Oceanside

State/Province

California

Country

United States

Facility Name

City

San Marcos

State/Province

California

Country

United States

Facility Name

City

Torrance

State/Province

California

Country

United States

Facility Name

City

New London

State/Province

Connecticut

Country

United States

Facility Name

City

Coral springs

State/Province

Florida

Country

United States

Facility Name

City

North Miami

State/Province

Florida

Country

United States

Facility Name

City

St. Petersburg

State/Province

Florida

Country

United States

Facility Name

City

Atlanta

State/Province

Georgia

Country

United States

Facility Name

City

Marietta

State/Province

Georgia

Country

United States

Facility Name

City

Chicago

State/Province

Illinois

Country

United States

Facility Name

City

Libertyville

State/Province

Illinois

Country

United States

Facility Name

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Oak Brook

State/Province

Illinois

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United States

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New Orleans

State/Province

Louisiana

Country

United States

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Baltimore

State/Province

Maryland

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United States

Facility Name

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Glen Burnie

State/Province

Maryland

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United States

Facility Name

City

Westminster

State/Province

Maryland

Country

United States

Facility Name

City

Pittsfield

State/Province

Massachusetts

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United States

Facility Name

City

Columbia

State/Province

Missouri

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United States

Facility Name

City

Clementon

State/Province

New Jersey

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United States

Facility Name

City

Moorestown

State/Province

New Jersey

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United States

Facility Name

City

Toms River

State/Province

New Jersey

Country

United States

Facility Name

City

Dayton

State/Province

Ohio

Country

United States

Facility Name

City

Medford

State/Province

Oregon

Country

United States

Facility Name

City

Salem

State/Province

Oregon

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United States

Facility Name

City

Sellersville

State/Province

Pennsylvania

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United States

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Lincoln

State/Province

Rhode Island

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United States

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Dallas

State/Province

Texas

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United States

Facility Name

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Salt Lake City

State/Province

Utah

Country

United States

Facility Name

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Richmond

State/Province

Virginia

Country

United States

Facility Name

City

Waukesha

State/Province

Wisconsin

Country

United States

Facility Name

City

St John's

State/Province

Newfoundland and Labrador

Country

Canada

Facility Name

City

Kingston

State/Province

Ontario

Country

Canada

Facility Name

City

St. John

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

22967772

Citation

Houston JP, Kohler J, Bishop JR, Ellingrod VL, Ostbye KM, Zhao F, Conley RR, Poole Hoffmann V, Fijal BA. Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia. J Clin Psychiatry. 2012 Aug;73(8):1077-86. doi: 10.4088/JCP.11m06916.

Results Reference

derived

PubMed Identifier

22480387

Citation

Houston JP, Lau K, Aris V, Liu W, Fijal BA, Heinloth AN, Perlis RH. Association of common variations in the norepinephrine transporter gene with response to olanzapine-fluoxetine combination versus continued-fluoxetine treatment in patients with treatment-resistant depression: a candidate gene analysis. J Clin Psychiatry. 2012 Jun;73(6):878-85. doi: 10.4088/JCP.10m06744. Epub 2012 Mar 6.

Results Reference

derived

PubMed Identifier

21095016

Citation

Houston J, Dharia S, Bishop JR, Ellingrod VL, Fijal B, Jacobson JG, Hoffmann VP. Association of DRD2 and ANKK1 polymorphisms with prolactin increase in olanzapine-treated women. Psychiatry Res. 2011 May 15;187(1-2):74-9. doi: 10.1016/j.psychres.2010.10.020. Epub 2010 Nov 20.

Results Reference

derived

PubMed Identifier

20361905

Citation

Tohen M, Case M, Trivedi MH, Thase ME, Burke SJ, Durell TM. Olanzapine/fluoxetine combination in patients with treatment-resistant depression: rapid onset of therapeutic response and its predictive value for subsequent overall response in a pooled analysis of 5 studies. J Clin Psychiatry. 2010 Apr;71(4):451-62. doi: 10.4088/JCP.08m04984gre. Epub 2010 Feb 23.

Results Reference

derived

PubMed Identifier

17335320

Citation

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. doi: 10.4088/jcp.v68n0207.

Results Reference

derived

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

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