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

• ClinicalTrials.gov Identifier: NCT01808651
• Recruitment Status: Completed
• First Posted: March 11, 2013
• Results First Posted: November 26, 2015
• Last Update Posted: November 26, 2015
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Fluoxetine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 200 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: May 2013
• Actual Primary Completion Date: March 2015
• Actual Study Completion Date: March 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fluoxetine; Flexible dosing of 20 to 40 milligrams (mg) administered orally, once daily, for approximately 52 weeks	Drug: Fluoxetine; Administered orally; Other Names: LY110140; Fluoxetine Hydrochloride; Prozac; Sarafem

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: Baseline through Week 52. ]
2. Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia - Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline through Week 52 ]
   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.

Secondary Outcome Measures :

1. Mean Change From Baseline to Week 52 on the 21-Item Hamilton Depression Rating Scale (HAMD21) Total Score [ Time Frame: Baseline, Week 52 ]
   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.
2. Percentage of Participants Achieving a Response at Week 52 [ Time Frame: Baseline, up to 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.
3. Percentage of Participants Achieving a Remission at Week 52 [ Time Frame: up to 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.
4. Mean Change From Baseline to Week 52 on the Clinical Global Impression of Severity (CGI-S) Scale [ Time Frame: Baseline, Week 52 ]
   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.
5. Mean Change From Baseline to Week 52 on the HAMD21 Subscale Scores [ Time Frame: Baseline, Week 52 ]
   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.
6. Change From Baseline to Week 52 in Sheehan Disability Scale (SDS) Total Score and Subscale Scores [ Time Frame: Baseline up to 52 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Japan

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.

Aichi, Japan, 471-8513

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.

Chiba, Japan, 270-0014

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.

Fukuoka, Japan, 800-0226

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.

Fukushima, Japan, 963-877

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.

Hiroshima, Japan, 737-0143

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.

Hokkaido, Japan, 065-0012

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.

Hyogo, Japan, 651-0097

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.

Kanagawa, Japan, 238-0042

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.

Kyoto, Japan, 616-8421

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.

Nagano, Japan, 390-0303

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.

Okayama, Japan, 700-0907

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.

Osaka, Japan, 586-0012

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.

Saitama, Japan, 339-0057

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.

Shiga, Japan, 525-0037

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.

Tochigi, Japan, 321-0953

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.

Tokyo, Japan, 170-0002

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: 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

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01808651
• Other Study ID Numbers: 14596; B1Y-JE-HCLW ( Other Identifier: Eli Lilly and Company )
• First Posted: March 11, 2013
• Results First Posted: November 26, 2015
• Last Update Posted: November 26, 2015
• Last Verified: October 2015

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; Fluoxetine; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors