A Study of Fluoxetine in Major Depressive Disorder (MDD) Long-Term Dosing

Study Overview
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Brief Summary
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This study will evaluate the safety and effectiveness of fluoxetine flexible dosing in the treatment of MDD in adult Japanese participants. Participants who complete the short-term treatment phase of Study B1Y-JE-HCLV (NCT#: NCT01808612) will be allowed to enroll in this study, and receive fluoxetine treatment for an additional 52 weeks.

Official Title
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A Phase 3, Open-label, Long-Term Study to Evaluate the Safety of LY110140 Once Daily Dosing for 52-week in Japanese Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Fluoxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have completed Study B1Y-JE-HCLV (NCT#:NCT01808612) Agree to abstain from sexual activity or to use a reliable method of birth control Exclusion Criteria: Significant suicidal risk Have a current or previous diagnosis of bipolar disorder, psychotic depression, schizophrenia or other psychotic disorder, anorexia, bulimia, obsessive compulsive disorder, or post-traumatic stress disorder Have a history of substance abuse or dependence within the past 6 months, excluding caffeine and nicotine Need to use thioridazine or pimozide during the study Have a positive urine drug screen for drugs with abuse potential Female participants who are either pregnant, nursing, or have recently given birth, or male participants who are planning for their partners to be or become pregnant Have frequent or severe allergic reactions to multiple medications Have a serious or unstable medical illness or condition, or psychological condition Participants deemed ineligible by the investigator or sub-investigator for other reasons

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluoxetine<br>Flexible dosing of 20 to 40 milligrams (mg) administered orally, once daily, for approximately 52 weeks | Drug: Fluoxetine<br>* Administered orally<br>* Other names: Sarafem;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) or Serious AEs (SAEs) |  | Baseline through Week 52. | 
| Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia - Suicide Severity Rating Scale (C-SSRS) | C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. | Baseline through Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Week 52 on the 21-Item Hamilton Depression Rating Scale (HAMD21) Total Score | HAMD21 is a 21-item assessment used to measure depression severity. Items were rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score ranging from 0 (not at all depressed) to 64 (severely depressed). Least squares (LS) means were calculated using mixed-model repeated measures (MMRM) adjusting for the random effect of participant and fixed categorical effects of treatment, pooled investigative site, visit, and treatment-by-visit interaction, as well as the continuous fixed covariate of baseline HAMD21 total score. | Baseline, Week 52 | 
| Percentage of Participants Achieving a Response at Week 52 | The percentage of participants achieving a response (defined as a ≥50% improvement from baseline on the HAMD21 total score) was calculated by dividing the number of participants achieving a response at last observation by the total number of participants at risk, multiplied by 100. | Baseline, up to Week 52 | 
| Percentage of Participants Achieving a Remission at Week 52 | The percentage of participants achieving a remission (defined as a HAMD21 total score ≤7) was calculated by dividing the number of participants achieving a remission at last observation by the total number of participants at risk, multiplied by 100. | up to Week 52 | 
| Mean Change From Baseline to Week 52 on the Clinical Global Impression of Severity (CGI-S) Scale | CGI-S measures severity of illness at the time of assessment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). LS means were calculated using MMRM adjusting for the random effect of participant and fixed categorical effects of treatment, pooled investigative site, visit, and treatment-by-visit interaction, as well as the continuous fixed covariate of baseline CGI-S score. | Baseline, Week 52 | 
| Mean Change From Baseline to Week 52 on the HAMD21 Subscale Scores | HAMD17 total scores and subscale scores from the HAMD21 are presented. HAMD17 is a 17-item assessment of depression severity (total scores range from 0-52). The Maier subscale (Items 1, 2, 7-10) represents the core symptoms of depression (0-24). Anxiety/Somatization subscale (Items 10-13, 15, 17) evaluates severity of psychic and somatic manifestations of anxiety as well as agitation (0-18). Retardation/Somatization subscale (Items 1, 7, 8, 14) evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation (0-14). Sleep subscale (Items 4-6) assesses insomnia (0-6). Individual item scores may range from 0-4 or 0-2. Higher scores indicate more severe symptoms. LS means were calculated using MMRM adjusting for the random effect of participant and fixed categorical effects of treatment, pooled investigative site, visit, and treatment-by-visit interaction, as well as the continuous fixed covariate of baseline score. | Baseline, Week 52 | 
| Change From Baseline to Week 52 in Sheehan Disability Scale (SDS) Total Score and Subscale Scores | SDS was completed by the participant and was used to assess the effect of the participant's symptoms on their work/school (Item 1), social life/leisure activities (Item 2), and family life/home responsibilities (Item 3). Each item was measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Total score was the sum of the 3 items and ranged from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. LS means were calculated using analysis of covariance (ANCOVA) adjusting for treatment, pooled investigative site, and baseline SDS score. | Baseline up to 52 weeks |