AzTrials
AzTrials

Treatment Resistant DepressionPhase 3NCT01687478

A Study of Olanzapine and Fluoxetine for Treatment-resistant Depression

A Phase 3 study testing Olanzapine and Fluoxetine in people with Treatment Resistant Depression, run by Eli Lilly and Company at 11 sites in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Treatment Resistant Depression
What is being tested?
Olanzapine and Fluoxetine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
176 participants
Where
11 sitesChina
Study dates
Sep 2012to Nov 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

China11 sites
  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

Other trials in China

About this study

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

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.

Being tested
Olanzapine, Fluoxetine, Placebo
Medical subject headings
Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlanzapineDrug

    Also called LY170053, Zyprexa

    Administered Orally

  • FluoxetineDrug

    Also called LY110140, Prozac

    Administered Orally

  • PlaceboDrug

    Administered Orally

Study groups in NCT01687478
Study groupRoleWhat they receive
Olanzapine + FluoxetineExperimentalOlanzapine 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.
Receives: Drug: Olanzapine; Drug: Fluoxetine
Placebo + FluoxetinePlacebo comparatorPlacebo 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.
Receives: Drug: Fluoxetine; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, 8 Weeks

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

    CGI-S scale measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The LS mean (LSM) change from baseline, standard error was derived using MMRM methodology with factors for treatment , Pooled Investigator , Visit , (Baseline + Treatment)*Visit.

    Measured: Baseline, 8 Weeks

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

    SAS scale consists of 10 items including 7 items that address bradykinesia-rigidity and additional single items for tremor, glabellar tap,and salivation. Each item represents a specific physical condition and is rated on a 5-point category rating scale ranging from 0 (complete absence of the condition) to 4 (the condition is present to an extreme degree).The total score is obtained by adding the scores for the 10 individual items making the maximum possible score is 40. Higher scores are indicative of more severe Parkinsonian-type symptoms.

    Measured: Baseline, 8 Weeks

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

    SF-36, version 2 is a generic participant-rated questionnaire and consists of 36 questions covering the following 8 health domains (subscales): general health, role limitations because of physical problems, role limitations due to emotional problems, physical functioning, bodily pain, mental health, social functioning, and vitality. Each subscale is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. Two summary scores, the physical component summary (PCS) and the mental component summary (MCS) were constructed based on the eight SF-36 subscales. Both PCS and MCS range from 0-100 with higher scores indicating better health or functioning.

    Measured: Baseline, 8 Weeks

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

    SDS consists of 3 items (work/school, social life/leisure activities, and family life/home responsibilities). Total scores range from 0 to 30 with higher values indicating greater disruption. Individual Item scores range from 0 to 10 with higher values indicating greater disruption.

    Measured: Baseline, 8 Weeks

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

    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.

    Measured: Baseline,8 Weeks

  6. Percentage of Participants Who Achieve Remission Based on MADRS Total Score ≤10 at 8 Weeks

    The MADRS consists of 10 items with each item rated on a scale ranging from 0 to 6. Fixed descriptors appear along the scale for each item at points 0, 2, 4, and 6, to standardize the gradation of response along the scale. 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.

    Measured: Baseline, 8 Weeks

  7. Mean Change From Baseline to 8 Week Endpoint in the Barnes Akathisia Scale (BAS)

    BAS is used to rate observable, restless movements of drug induced akathisia and the subjective awareness of restlessness and any distress associated with the akathisia. The BAS consists of the following 3 items: an objective assessment of akathisia symptoms; a subjective assessment of the patient's awareness of inner restlessness; and a global clinical assessment of akathisia. The first two items are rated on a 4-point scale ranging from 0 (no abnormal movements or the absence of inner restlessness) to 3 (severe akathisia or the awareness of intense compulsion to move most of the time). The last item, the global clinical assessment of akathisia, is rated on a 5-point scale, ranging from 0 (no evidence of akathisia) to 5 (severe akathisia). Total BAS score ranges from 0 to 14 with a higher score representing worse results.

    Measured: Baseline, 8 Weeks

  8. Mean Change From Baseline to 8 Week Endpoint in the Abnormal Involuntary Movement Scale (AIMS)

    AIMS is a 12-item scale. Items 1 to 8 are rated on a 5-point scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Item 9 assesses the participant's incapacitation due to abnormal movements, and item 10 assesses the participant's awareness of the abnormal movements and associated distress. Items 9 and 10 are rated on 5-point scales ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Items 11 and 12 are yes/no questions regarding the dental status of the participant. The total score is the sum of the scores for the 12 items and the possible total score ranges from 0 to 42. A higher total score is indicative of more severe dyskinetic movements.

    Measured: Baseline, 8 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionNov 2015
  4. Study completionNov 2015

Why it stopped: Interim assessment: Lack of efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
176 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01687478
Sponsor's protocol ID
13702
Other IDs
F1D-CR-HGNB
Status last verified
Sep 2019
First submitted
7 Sep 2012
Last updated
9 Oct 2019
Data monitoring committee
No
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Olanzapine and Fluoxetine in people with Treatment Resistant Depression, run by Eli Lilly and Company at 11 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline to 8 Week Endpoint in Montgomery-Äsberg Depression Rating Scale (MADRS) (time frame: Baseline, 8 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2019.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in