A Study in Participants With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor

Lilly

Status and phase: Completed; Phase 3

Conditions: Major Depressive Disorder

Treatments: Drug: SSRI; Drug: Placebo; Drug: LY2216684

Study type: Interventional

Funder types: Industry

Identifiers

NCT01185340

H9P-MC-LNBR (Other Identifier)

12183

Details and patient eligibility

About

The primary objective of this study is to assess whether LY2216684 12 milligrams (mg) or 18 mg flexible dose once daily is superior to placebo once daily in the adjunctive treatment of participants with major depressive disorder (MDD) who are partial responders to their selective serotonin reuptake inhibitor (SSRI) treatment.

Full description

Following the Confirmation (CF) Phase, participants were randomized to adjunctive LY2216684 or adjunctive placebo if they had <25% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score over the past 3 weeks and a current MADRS total score ≥14. Participants who did not meet criteria received adjunctive placebo to preserve the blind.

Enrollment: 1,056 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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 being treated with one of the following selective serotonin reuptake inhibitors (SSRIs): escitalopram, citalopram, sertraline, fluoxetine, paroxetine, or fluvoxamine; for at least 6 weeks prior to investigational product dispensing with at least the last 4 weeks at a stable, optimized dose
• Drug and dosage should be within the labeling guidelines for the specific country
• Meet criteria for major depressive disorder (MDD), as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision® (DSM-IV-TR) criteria
• Meet criteria for partial response, as defined by investigator's opinion that the participant has experienced a minimal clinically meaningful improvement with SSRI
• Have a GRID 17-Item Hamilton Depression Rating Scale (GRID-HAMD17) total score greater than or equal to 16 at screening
• Have less than or equal to 75% improvement on the current SSRI at screening determined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ)

Exclusion criteria

• Have had or currently have any additional ongoing 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 [OCD], post-traumatic stress disorder [PTSD], generalized anxiety disorder [GAD], 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 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
• Unstable medical conditions that contraindicate the use of LY2216684
• Have any diagnosed medical condition that could be exacerbated by noradrenergic agents, including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angled glaucoma, history of urinary hesitancy or retention
• Use of excluded concomitant or psychotropic medication other than SSRI
• Have initiated or discontinued hormone therapy within the 3 months prior to enrollment
• History of treatment-resistant depression as shown by lack of response of the current depressive episode to 2 or more adequate courses of antidepressant therapy at a clinically appropriate dose for at least 4 weeks or, in the judgment of the investigator, the participant has treatment-resistant depression
• Have a lifetime history of vagal nerve stimulation (VNS), transcranial magnetic stimulation (TMS), or psychosurgery
• Have received electroconvulsive therapy (ECT) in the past year

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,056 participants in 2 patient groups, including a placebo group

LY2216684 + SSRI

Experimental group

Description:

LY2216684: flexible dose of 12 or 18 milligrams (mg), administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Prior to entering the Adjunctive Treatment (AT) Phase, participants completed a 3-week Confirmation (CF) Phase where they received placebo (administered orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to the LY2216684 treatment arm. For the first 2 weeks of the AT Phase, participants received a starting dose of 12 mg QD. Then, based on efficacy and tolerability, the dose could be increased to 18 mg QD over the next 6 weeks. Participants who had their dose increased to 18 mg QD could have had their dose decreased to 12 mg QD. Participants who completed the AT Phase or discontinued early had the option to enter the Discontinuation (DC) Phase. During the 1-week abrupt DC Phase, participants maintained their SSRI treatment.

Treatment:

Drug: LY2216684

Drug: Placebo

Drug: SSRI

Placebo + SSRI

Placebo Comparator group

Description:

Placebo: Administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI) Prior to entering the Adjunctive Treatment (AT) Phase, participants completed a 3-week Confirmation (CF) Phase where they received placebo (administered orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to the placebo treatment arm. During the AT Phase, participants received placebo (administered orally, QD) adjunctive to their SSRI for 8 weeks. Participants who completed the AT Phase or discontinued early had the option to enter the Discontinuation (DC) Phase. During the 1-week abrupt DC Phase, participants maintained their SSRI treatment.

Treatment:

Drug: Placebo

Drug: SSRI