A Study of Olanzapine and Fluoxetine for Treatment-resistant Depression

NCT01687478 | Terminated Phase 3 Results

• 2 other identifiers: 13702F1D-CR-HGNB
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to assess the efficacy and safety of olanzapine and fluoxetine compared to placebo and fluoxetine as treatment for treatment-resistant depression (TRD) in Chinese participants.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline to 8 Week Endpoint in Montgomery-Äsberg Depression Rating Scale (MADRS)

  The MADRS total score is the sum of the 10 items; therefore the possible MADRS total score ranges from 0 to 60. A higher MADRS total score indicates a greater severity of depressive symptoms. Least square means (LSM) change from baseline, standard error was derived using mixed model repeated measures (MMRM) methodology with factors for treatment, Pooled Investigator, Visit, (Baseline + Treatment)\*Visit.

  Baseline, 8 Weeks

Secondary Outcomes (8)

• Mean Change From Baseline to 8 Week Endpoint in Clinical Global Impressions-Severity of Depression (CGI-S) Scale

  Baseline, 8 Weeks

• Mean Change From Baseline to 8 Week Endpoint in the Simpson-Angus Scale (SAS)

  Baseline, 8 Weeks

• Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)

  Baseline, 8 Weeks

• Mean Change From Baseline to 8 Week Endpoint in the Sheehan Disability Scale (SDS)

  Baseline, 8 Weeks

• Percentage of Participants Who Achieve a Response Based on a ≥50% Reduction From Baseline in MADRS Total Score

  Baseline,8 Weeks

Study Arms (2)

Olanzapine + Fluoxetine

EXPERIMENTAL

Olanzapine starting dose is 5 milligram (mg) (1 tablet). May titrate up to 10 mg (2 tablets), or 15 mg (3 tablets) administered once daily by mouth for 8 weeks. Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.

Drug: Olanzapine; Drug: Fluoxetine

Placebo + Fluoxetine

PLACEBO COMPARATOR

Placebo matches the Olanzapine tablet for blinding. Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.

Drug: Fluoxetine; Drug: Placebo

Interventions

Olanzapine DRUG

Administered Orally

Also known as: LY170053, Zyprexa

Olanzapine + Fluoxetine

Fluoxetine DRUG

Administered Orally

Also known as: LY110140, Prozac

Olanzapine + Fluoxetine; Placebo + Fluoxetine

Placebo DRUG

Administered Orally

Placebo + Fluoxetine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have single or recurrent unipolar major depressive disorder (MDD) without psychotic features by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) clinical assessment
• Have a total score ≥22 on the 17-item Hamilton Depression Rating Scale (HAM-D17) at screening and randomization
• Have treatment-resistant depression (TRD), defined as having failed to achieve a satisfactory antidepressant response, in the opinion of the investigator, to separate treatment courses of at least 2 different antidepressants, other than fluoxetine, of adequate dosage and duration (≥6 weeks) within the current major depressive episode

You may not qualify if:

• Have a diagnosis of Parkinson's disease or a related disorder
• Have a current or lifetime diagnosis of any of the following conditions, according to DSM-IV-TR criteria: Schizophrenia; Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder; Psychotic Disorder Not Otherwise Specified; Bipolar Disorder I or II; Delirium of any type; Dementia of any type; Amnestic Disorder; any Substance-Induced Disorder; or any Psychotic Disorder due to a General Medical Condition
• Have a current diagnosis of post-partum depression or MDD with a seasonal pattern as defined in the DSM-IV-TR
• Have paranoid, schizoid, schizotypal, antisocial, or borderline personality disorder (Axis II) as a comorbid or primary diagnosis, based on DSM-IV-TR criteria
• Have DSM-IV-TR substance dependence/abuse or are not willing to avoid use of the substance (not including dependence on nicotine or caffeine) within 30 days of screening
• Are actively suicidal in the judgment of the investigator
• Have uncorrected narrow-angle glaucoma
• Have had one or more seizures without a clear and resolved etiology
• Have leukopenia
• Have any acute, serious, or unstable medical conditions
• Have an increased serum prolactin concentration at screening
• Have a rate-corrected cardiac QT interval, calculated using Bazett's formula (QTc Bazett's \[Rate-corrected cardiac QT interval on electrocardiogram calculated using Bazett's formula(QTcB)\]), on Electrocardiogram (ECG) \>450 milliseconds (male) or \>470 milliseconds (female) at screening
• Have a history of allergic reaction to olanzapine, fluoxetine, or olanzapine in combination with fluoxetine
• Have had treatment with olanzapine, fluoxetine, or olanzapine in combination with fluoxetine withdrawn due to clinically significant and/or intolerable adverse effects within 6 months of screening
• Have received treatment with remoxipride within 6 months of randomization

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (11)

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

Baoding, 071000, China

Location

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

Beijing, 100088, China

Location

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

Changsha, 410011, China

Location

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

Guangzhou, 510080, China

Location

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

Hangzhou, 310009, China

Location

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

Kunming, 650032, China

Location

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

Nanjing, 210029, China

Location

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

Shanghai, 200030, China

Location

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

Wuhan, 430022, China

Location

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

Xi'an, 710061, China

Location

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

Xinxiang, 453002, China

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Olanzapine; Fluoxetine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2012
• First Posted: September 19, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: October 9, 2019
• Results First Posted: August 24, 2017

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

CN (11)