A Fixed Dose Study of Adjunctive Treatment to Antidepressant Therapy for Adults With Major Depressive Disorder

Official Title: “A Randomized, Placebo-Controlled, Double-Blind Study of LY2216684 Fixed-Dose 12 mg and 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment”

The primary purpose of this study is to assess whether at least one dose of LY2216684 (12 mg or 18 mg once daily) is superior to placebo once daily in the adjunctive treatment of patients with major depressive disorder (MDD) who were identified as partial responders to an adequate course of treatment with a selective serotonin reuptake inhibitor (SSRI), during an 11-week, double-blind, acute adjunctive treatment phase.

Intervention(s) in this Clinical Trial

• Drug: LY2216684
  • Taken by mouth once daily
• Drug: Placebo
  • Taken by mouth once daily for 11 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 12 mg LY2216684
  • 12 mg for 11 weeks
• Experimental: 18 mg LY2216684
  • 12 mg for 1 week followed by 18 mg for 10 weeks
• Placebo Comparator: Placebo

Primary Measures

• Change from baseline to week 11 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No

Secondary Measures

• Change from baseline to week 11 in Sheehan Disability Scale (SDS) Global Functional Impairment scale
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in Fatigue Associated with Depression (FAsD) impact subscale score
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Percentage of patients achieving a MADRS total score of less than or equal 10 at week 11
  • Time Frame: 11 weeks
    Safety Issue?: No
• Percentage of patients achieving a MADRS total score of less than or equal 10 at 2 consecutive measurements including the patient's last measurement
  • Time Frame: Through 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in Hospital and Anxiety and Depression Scale (HADS) anxiety subscale score
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Percent of patients who have a greater than or equal to 50 percent improvement in the MADRS total score from baseline to week 11
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in HADS depression subscale score
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in MADRS individual items
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in Clinical Global Impressions of Severity (CGI-S)
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in FAsD average score and experience subscale score
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in Sheehan Disability Scale (SDS) items
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Change from baseline to week 11 in the EuroQol Questionnaire-5 Dimension (EQ-5D)
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: No
• Percentage of treatment emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
  • Time Frame: Through 13 weeks
    Safety Issue?: Yes
• Change from baseline to week 11 in Arizona Sexual Experiences (ASEX) scale
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: Yes
• Change from baseline to week 11 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: Yes
• The number of patients experiencing treatment emergent adverse events as a function of CYP2D6 genotype
  • Time Frame: Through 11 weeks
    Safety Issue?: Yes
• Change from baseline to week 11 in blood pressure
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: Yes
• Change from baseline to week 11 in pulse rate
  • Time Frame: Baseline, 11 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• Clinical diagnosis of Major Depressive Disorder (MDD)
• Women of child-bearing potential may participate but must test negative for pregnancy at the time of study entry; both women/men agree to use a reliable method of birth control
• Are taking an SSRI approved for MDD treatment within the patient's country and the SSRI prescribed, including dose, should be consistent with labeling guidelines within the participating country
• Have a partial response to SSRI treatment
• Meet inclusion scores on pre-defined psychiatric scales to assess diagnosis of depression, disease severity, and response to SSRI treatment
• Reliable and able to keep all scheduled appointments

Exclusion Criteria:

• Presence of another primary psychiatric illness:
• Have had or currently have any additional ongoing Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) Axis 1 condition other than major depression within 1 year of screening
• Have had any anxiety disorder that was considered a primary diagnosis within the past year (including panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and social phobia, but excluding specific phobias)
• Have a current or previous diagnosis of a bipolar disorder, schizophrenia, or other psychotic disorder
• Have a history of substance abuse and/or dependence within the past 1 year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine.
• Have an Axis II disorder that, in the judgment of the investigator, would interfere with compliance with protocol
• Have any diagnosed medical condition which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angle glaucoma, urinary hesitation or retention
• Use of excluded concomitant or psychotropic medication other than SSRI
• Have initiated or discontinued hormone therapy within the previous 3 months of prior to enrollment
• Have treatment resistant depression
• Have a lifetime history of vagal nerve stimulation, transcranial magnetic stimulation, or psychosurgery
• Have received electroconvulsive therapy in the last year
• Enrollment in a clinical study for an investigational drug
• Serious or unstable medical condition
• History of seizure disorders
• Have initiated psychotherapy or other nondrug therapies (such as acupuncture or hypnosis) within 12 weeks prior to enrollment or any time during the study. No change in intensity of psychotherapy within the last 6 weeks prior to enrollment or at any time during the study.
• Patients who, in the opinion of the investigator, are judged to be at serious risk for harm to self or others

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eli Lilly and Company Industry

Overall Clinical Trial Officials and Contacts

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) Study Director Eli Lilly and Company  

Overall Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) 1-317-615-4559 

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01173601

Study ID Number: 11316

ClinicalTrials.gov Identifier: NCT01173601

Health Authority: United States: Food and Drug Administration