Efficacy and Safety of Flexibly Dosed BMS-820836 in the Treatment of Patients With Treatment Resistant Major Depression

• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase B: Baseline ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Screening Visit ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase B: weeks 2 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase B: weeks 4 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase B: weeks 6 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase B: weeks 8 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase C: weeks 9 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase C: weeks 10 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase C: weeks 11 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase C: weeks 12 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase C: weeks 13 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms from end of Phase B to end of Phase C, last observation carried forward (LOCF) in the Montgomery Asberg Depression Rating Scale (MADRS) total score. [ Time Frame: Phase C: weeks 14 ] [ Designated as safety issue: No ]

• Change in Sheehan Disability Scale (SDS) Total score [ Time Frame: End of Phase B and End of Phase C ] [ Designated as safety issue: No ]
• Change in the Montgomery Asberg Depression Rating Scale (MADRS) anhedonia factor score [ Time Frame: End of Phase B and End of Phase C ] [ Designated as safety issue: No ]

• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 2 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 4 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 6 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 8 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 9 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 10 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 11 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 12 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 13 ] [ Designated as safety issue: No ]
• A reduction in depressive symptoms at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by an improvement of Clinical Global Impression (CGI) score. [ Time Frame: Weeks 14 ] [ Designated as safety issue: No ]
• A change in functional impairment at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by the Sheehan Disability Scale (SDS) score. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• A change in functional impairment at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by the Sheehan Disability Scale (SDS) score. [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
• A change in functional impairment at the end of Phase C (Week 14, last observation carried forward [LOCF]) measured by the Sheehan Disability Scale (SDS) score. [ Time Frame: Week 14 ] [ Designated as safety issue: No ]

The purpose of the study is to evaluate the efficacy of study drug (BMS-820836) as compared with continued duloxetine in the treatment of patients with treatment resistant depression (TRD).

• Drug: Duloxetine
  Capsule, Oral, 30-60 mg/day, once daily (QD), 8 weeks
  Other Name: Cymbalta
• Drug: Placebo matching with BMS-820836
  Tablet, Oral, 0.0 mg, once daily (QD), 14 weeks
• Drug: BMS-820836
  Tablet, Oral, 0.5-2.0 mg, once daily (QD), 6 weeks
• Drug: Duloxetine
  Capsule, Oral, 30-60 mg/day, once daily (QD), 6 weeks
  Other Name: Cymbalta
• Drug: Placebo matching with Duloxetine
  Tablet, Oral, 0.0 mg, once daily (QD), 8 weeks

• Active Comparator: Arm 1: Duloxetine 30mg
  Intervention: Drug: Duloxetine
• Placebo Comparator: Arm 2: BMS-820836 placebo
  Intervention: Drug: Placebo matching with BMS-820836
• Experimental: Arm 3: BMS-820836 0.5-2.0 mg/day
  Intervention: Drug: BMS-820836
• Active Comparator: Arm 4: Duloxetine 30mg
  Intervention: Drug: Duloxetine
• Placebo Comparator: Arm 5: Duloxetine placebo
  Intervention: Drug: Placebo matching with Duloxetine

Inclusion Criteria:

• Patients must be able to understand the nature of the study, agree to comply with the prescribed dosage regimens, report for regularly scheduled office visits, and communicate to study personnel about adverse events and concomitant medication use.
• Patients with a diagnosis of Major Depressive Disorder, currently experiencing a Major Depressive Episode, as defined by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition Text Revision(DSM IV TR) criteria. The current depressive episode must be > 8 weeks in duration and < 3 years duration.
• In the current Major Depressive Disorder (MDD) episode, patients should report a history of inadequate response to 1 - 3 adequate trials of antidepressant treatment.
• Patients must have a 17-item Hamilton Depression Rating Scale (HAM-D17) total score =>18 at Screening.

Exclusion Criteria:

• Patients who report an inadequate response (less than 50% reduction in depressive symptom severity) to more than three adequate trials of antidepressant treatments during the current depressive episode.
• Patients who have failed duloxetine at an adequate dose and for an adequate duration in their current episode unless in the judgment of the investigator, the patient could benefit from the treatment with this medication.
• Patients whose only inadequate response to an antidepressant in the current Major Depressive Episode (MDE) is to an Serotonin norepinephrine reuptake inhibitors (SNRI) (duloxetine, venlafaxine, desvenlafaxine or milnacipran).