Phase 3
N=892
A Study in Relapse Prevention of Treatment-Resistant Depression
Treatment Resistant Depression
Bottom Line
View on ClinicalTrials.gov: NCT00958568 ↗Enrolled (actual)
892
Serious AEs
1.9%
Results posted
Apr 2014
Primary outcome: Primary: Time to Relapse by Any Criteria — NA; NA days — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Olanzapine and Fluoxetine combination (OFC) (Drug); Fluoxetine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Eli Lilly and Company
- Primary completion
- Mar 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Relapse by Any Criteria |
NA; NA | <0.001 sig |
| SECONDARY Percentage of Participants Who Relapse by Any Criteria |
15.8; 31.8 | <0.001 sig |
| SECONDARY Percentage of Participants Who Relapse Based on Montgomery-Åsberg Depression Rating Scale (MADRS) Score With Concomitant Clinical Global Impressions-Severity (CGI-S) of Depression Score |
14.0; 28.3 | <0.001 sig |
| SECONDARY Percentage of Participants Who Relapse as Measured by Hospitalization for Depression or Suicidality |
1.8; 1.3 | 0.713 |
| SECONDARY Percentage of Participants Who Relapse as Measured by Discontinuation Due to Lack of Efficacy/Worsening of Depression/Suicidality |
10.9; 28.3 | <0.001 sig |
| SECONDARY Time to Relapse Based on the Montgomery-Åsberg Depression Rating Scale (MADRS) Score With Concomitant Clinical Global Impressions-Severity (CGI-S) of Depression Score |
NA; NA | <0.001 sig |
| SECONDARY Time to Relapse as Measured by Hospitalization for Depression or Suicidality |
NA; NA | 0.831 |
| SECONDARY Time to Relapse as Measured by Discontinuation Due to Lack of Efficacy/Worsening of Depression/Suicidality |
NA; NA | <0.001 sig |
| SECONDARY Percentage of Participants Responding to Treatment During Open-Label Acute Treatment Phase |
78.0 | — |
| SECONDARY Percentage of Participants Maintaining Response at Any Point During Stabilization Treatment Phase |
68.2 | — |
| SECONDARY Percentage of Participants Achieving Remission at Any Point During Stabilization Treatment Phase |
77.9 | — |
| SECONDARY Percentage of Participants Maintaining Remission |
86.4; 78.9 | 0.047 sig |
| SECONDARY Mean Change From Week 20 to Week 47 in Montgomery-Asberg Depression Rating Scale (MADRS) Using Mixed-Effects Model Repeated Measures (MMRM) Analysis |
2.06; 4.97 | <0.001 sig |
| SECONDARY Mean Change From Week 20 to Week 47 in Montgomery-Asberg Depression Rating Scale (MADRS) Using Last Observation Carried Forward (LOCF) Analysis |
3.03; 6.84 | <0.001 sig |
| SECONDARY Mean Change From Week 20 to Week 47 in Clinical Global Impressions - Severity (CGI-S) of Depression Using Mixed-Effects Model Repeated Measures (MMRM) Analysis |
0.20; 0.54 | 0.002 sig |
| SECONDARY Resource Utilization - Average Number of Hours Worked for Pay Per Week at Week 47 |
37.49; 37.76 | — |
| SECONDARY Resource Utilization (Number of Psychiatric Visits, Number of Emergency Room or Equivalent Facility Visits for Psychiatric Illness) |
0.65; 0.81; 0.00; 0.00 | — |
| SECONDARY Change From Week 20 to Week 47 Endpoint in the Sheehan Disability Scale (SDS) |
1.30; 3.24 | 0.007 sig |
| SECONDARY Percent of Participants With Treatment-Emergent Akathisia |
0.9; 0.9 | 1.00 |
| SECONDARY Percent of Participants With Treatment-Emergent Parkinsonism |
1.4; 0.0 | 0.248 |
| SECONDARY Percent of Participants With Treatment-Emergent Dyskinesia |
0.5; 0.0 | 1.00 |
| SECONDARY Mean Change From Week 20 to Week 47 in Fasting Total Cholesterol |
-2.65; -1.74 | 0.839 |
| SECONDARY Percent of Participants With Treatment-Emergent High Fasting Total Cholesterol |
28.0; 20.5; 17.0; 16.9; 2.1; 3.4 | 0.352 |
| SECONDARY Mean Change From Week 20 to Week 47 in Fasting Low-Density Lipoprotein (LDL) Cholesterol |
-0.72; 0.85 | 0.703 |
| SECONDARY Percent of Participants With Treatment-Emergent High Fasting Low-Density Lipoprotein (LDL) Cholesterol |
17.4; 10.4; 22.7; 30.8; 4.5; 0.0 | 0.139 |
| SECONDARY Mean Change From Week 20 to Week 47 in Fasting High-Density Lipoprotein (HDL) Cholesterol |
-1.71; 2.02 | 0.001 sig |
| SECONDARY Percent of Participants With Treatment-Emergent Low Fasting High-Density Lipoprotein (HDL) Cholesterol |
39.2; 25.5 | 0.004 sig |
| SECONDARY Percent of Participants With Treatment-Emergent Hepatic Events |
0.0; 0.0 | 1.00 |
| SECONDARY Mean Change From Week 20 to Week 47 in Fasting Triglycerides |
-8.24; -21.51 | 0.083 |
| SECONDARY Percent of Participants With Treatment-Emergent High Fasting Triglycerides |
51.1; 26.8; 22.1; 6.8; 16.2; 5.4 | 0.029 sig |
| SECONDARY Mean Change From Week 20 to Week 47 in Fasting Glucose |
3.67; -2.22 | 0.002 sig |
| SECONDARY Percent of Participants With Treatment-Emergent High Fasting Glucose |
18.4; 7.2; 4.4; 5.2; 35.6; 28.1 | 0.031 sig |
| SECONDARY Mean Change From Week 20 to Week 47 in Weight |
1.14; -2.78 | <0.001 sig |
| SECONDARY Percent of Participants With Week 20-to-Week 47 Endpoint Increase in Weight of at Least 7% |
11.8; 2.3 | <0.001 sig |
| SECONDARY Percent of Participants With Suicide-Related Thoughts and Behaviors |
4.1; 6.3; 0; 0 | 0.392 |
| SECONDARY Mean Change in Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) on Electrocardiogram |
-3.12; -1.55 | 0.421 |
| SECONDARY Percent of Participants With Treatment-Emergent Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) on Electrocardiogram ≥500 Milliseconds (Msec) |
0; 0 | — |
| SECONDARY Percent of Participants With a 60 Milliseconds (Msec) Increase in Fridericia-Corrected (for Rate) Cardiac QT Interval (QTcF) on Electrocardiogram |
0; 0 | — |
Summary
The purpose of this study is to determine whether olanzapine and fluoxetine combination (OFC) if used for a long time (47 weeks) makes patients suffering from Treatment Resistant Depression stable, determine if OFC is safe when used to treat patients with Treatment Resistant Depression for a long time (up to 47 weeks), to determine whether olanzapine and fluoxetine combination or fluoxetine alone is better to treat Treatment Resistant Depression when treated for a long time (up to 47 weeks) and to assess the quality of life during treatment.
Eligibility Criteria
Inclusion Criteria
- 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, confirmed by the structured clinician Interview for DSM-IV Axis 1 disorders (SCID-I).
- If female and of childbearing potential, test negative for pregnancy and agree to abstain from sexual activity or use a medically accepted means of contraception during the study. Use of any oral or injectable contraception must be initiated prior to receiving treatment.
- Have 17-item Hamilton Depression (HAM-D) score greater than or equal to 18 at screening and the day treatment is due to be received for the first time.
- Have treatment-resistant depression, as defined by having demonstrated failure to achieve satisfactory antidepressant response to adequate separate treatment courses of at least 2 different antidepressants within the current episode of MDD.
Exclusion Criteria
- Have a diagnosis of Parkinson's disease or related disorders.
- Have a current or lifetime diagnosis of any of the following according to DSM-IV 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 current diagnosis of post-partum depression, MDD with atypical features, or MDD with a seasonal pattern as defined in the DSM-IV.
- Have paranoid, schizoid, schizotypal, antisocial, and borderline personality disorders (Axis II) as a comorbid or primary diagnosis, based on DSM-IV criteria.
- Have had psychotic symptoms within 1 month prior to Screening or demonstrate psychotic features at screening and on the day treatment is due to be assigned for the first time as determined by the investigator.
- Have DSM-IV substance dependence/abuse or not willing to avoid use of the substance (not including dependence on nicotine or caffeine), as defined by the SCID-I, within the past 30 days.
- Are actively suicidal in the judgment of the investigator.
- Have had one or more seizures without a clear and resolved etiology.
- Have leukopenia or history of leukopenia without a clear and resolved etiology, or known history of agranulocytosis during the participant's lifetime.
- Have alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) values greater than or equal to 2 times the upper limit of normal (ULN) of the performing laboratory or aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) values greater than or equal to 2 times the ULN or total bilirubin values greater than or equal to 1.5 times the ULN at any time during screening.
- Have acute, serious, or unstable medical conditions.
- Have any illness such that death is anticipated within 1 year or intensive care unit hospitalization for the illness is anticipated within 6 months.
- Have elevated prolactin levels at screening.
- Have Bazett's corrected QT interval (QTc) greater than 450 milliseconds (male) or greater than 470 milliseconds (female) at screening and when treatment is due to be received for the first time.
- Have received electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS) treatment within the current episode; have a history of failure to adequate treatment courses of ECT or VNS; or will require ECT or VNS at any time during study participation.
- If receiving psychotherapy, light therapy, or both, are anticipated to require changes in frequency/intensity of treatment regimen or to cease treatment regimen over the duration of the study. Participants who are not receiving any of these therapies upon study entry may not begin any of these therapies during screening, or during any treatment phases of the study.
- Have received previous treatment wit
Data sourced from ClinicalTrials.gov (NCT00958568). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.