Clinical trial NCT01687478: A Study of Olanzapine and Fluoxetine for Treatment-resistant Depression
Official title: A Study to Assess the Short-Term Efficacy and Safety of Olanzapine and Fluoxetine Compared to Placebo and Fluoxetine for Nonpsychotic Treatment-Resistant Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Treatment Resistant Depression
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-09-19
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* 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

Exclusion Criteria:

* 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
* Have received treatment with depot antipsychotics within one dosing interval before randomization
* Have received electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS) treatment within the current MDD episode, or has a history of failure to respond to adequate treatment courses of ECT or VNS, or is expected to require ECT or VNS at any time during the study
* Have received previous treatment with clozapine
* Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of screening, or are expected to need MAOI treatment at any time during the study or up until 5 weeks after study discontinuation

Primary outcomes:
measure: Mean Change From Baseline to 8 Week Endpoint in Montgomery-Äsberg Depression Rating Scale (MADRS)
timeFrame: Baseline, 8 Weeks
Secondary outcomes:
measure: Mean Change From Baseline to 8 Week Endpoint in Clinical Global Impressions-Severity of Depression (CGI-S) Scale
timeFrame: Baseline, 8 Weeks
measure: Mean Change From Baseline to 8 Week Endpoint in the Simpson-Angus Scale (SAS)
timeFrame: Baseline, 8 Weeks
measure: Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
timeFrame: Baseline, 8 Weeks
measure: Mean Change From Baseline to 8 Week Endpoint in the Sheehan Disability Scale (SDS)
timeFrame: Baseline, 8 Weeks
measure: Percentage of Participants Who Achieve a Response Based on a ≥50% Reduction From Baseline in MADRS Total Score
timeFrame: Baseline,8 Weeks
measure: Percentage of Participants Who Achieve Remission Based on MADRS Total Score ≤10 at 8 Weeks
timeFrame: Baseline, 8 Weeks
measure: Mean Change From Baseline to 8 Week Endpoint in the Barnes Akathisia Scale (BAS)
timeFrame: Baseline, 8 Weeks
measure: Mean Change From Baseline to 8 Week Endpoint in the Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Baseline, 8 Weeks
Other outcomes:
Locations:
city: Baoding
country: China
facility: 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.
city: Beijing
country: China
facility: 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.
city: Changsha
country: China
facility: 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.
city: Guang Zhou
country: China
facility: 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.
city: Hangzhou
country: China
facility: 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.
city: Kunming
country: China
facility: 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.
city: Nanjing
country: China
facility: 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.
city: Shanghai
country: China
facility: 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.
city: Wuhan
country: China
facility: 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.
city: Xi'An
country: China
facility: 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.
city: Xinxiang
country: China
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: