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

NCT ID: NCT01185340

Last Updated: 2018-04-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1056 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-31

Study Completion Date

2013-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Major Depressive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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LY2216684 + SSRI

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.

Group Type EXPERIMENTAL

LY2216684

Intervention Type DRUG

Placebo

Intervention Type DRUG

SSRI

Intervention Type DRUG

Participants should have been on their SSRI for at least 6 weeks prior and were to continue on their stable dose throughout the study

Placebo + SSRI

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

SSRI

Intervention Type DRUG

Participants should have been on their SSRI for at least 6 weeks prior and were to continue on their stable dose throughout the study

Interventions

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LY2216684

Intervention Type DRUG

Placebo

Intervention Type DRUG

SSRI

Participants should have been on their SSRI for at least 6 weeks prior and were to continue on their stable dose throughout the study

Intervention Type DRUG

Other Intervention Names

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Edivoxetine selective serotonin reuptake inhibitor

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Garden Grove, California, United States

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Oakland, California, United States

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Temecula, California, United States

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Waterbury, Connecticut, United States

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Boca Raton, Florida, United States

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Fort Myers, Florida, United States

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North Bay Village, Florida, United States

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Oakland Park, Florida, United States

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Orlando, Florida, United States

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West Palm Beach, Florida, United States

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Shreveport, Louisiana, United States

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Lincoln, Nebraska, United States

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Marlton, New Jersey, United States

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Brooklyn, New York, United States

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New York, New York, United States

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Staten Island, New York, United States

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Cincinnati, Ohio, United States

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Media, Pennsylvania, United States

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Herndon, Virginia, United States

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Richmond, Virginia, United States

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Everton Park, Queensland, Australia

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Spring Hill, Queensland, Australia

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Frankston, Victoria, Australia

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Heidelberg, Victoria, Australia

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Malvern, Victoria, Australia

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Melbourne, Victoria, Australia

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Vienna, , Austria

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Diest, , Belgium

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Liège, , Belgium

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Mont-Godinne, , Belgium

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Bad Saarow, , Germany

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Berlin, , Germany

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Bochum, , Germany

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Cham, , Germany

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Dresden, , Germany

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Hattingen, , Germany

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Leipzig, , Germany

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Munich, , Germany

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Nuremberg, , Germany

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Prien am Chiemsee, , Germany

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Schwerin, , Germany

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Gothenburg, , Sweden

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Lund, , Sweden

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Malmo, , Sweden

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Solna, , Sweden

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Stockholm, , Sweden

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Bexhill-on-Sea, East Sussex, United Kingdom

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Glasgow, Scotland, United Kingdom

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Chesterfield, , United Kingdom

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Countries

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United States Australia Austria Belgium Germany Sweden United Kingdom

References

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Stauffer VL, Liu P, Goldberger C, Marangell LB, Nelson C, Gorwood P, Fava M. Is the Noradrenergic Symptom Cluster a Valid Construct in Adjunctive Treatment of Major Depressive Disorder? J Clin Psychiatry. 2017 Mar;78(3):317-323. doi: 10.4088/JCP.15m09972.

Reference Type DERIVED
PMID: 27685842 (View on PubMed)

Ball SG, Ferguson MB, Martinez JM, Pangallo BA, Nery ES, Dellva MA, Sparks J, Zhang Q, Liu P, Bangs M, Goldberger C. Efficacy outcomes from 3 clinical trials of edivoxetine as adjunctive treatment for patients with major depressive disorder who are partial responders to selective serotonin reuptake inhibitor treatment. J Clin Psychiatry. 2016 May;77(5):635-42. doi: 10.4088/JCP.14m09619.

Reference Type DERIVED
PMID: 27035159 (View on PubMed)

Other Identifiers

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H9P-MC-LNBR

Identifier Type: OTHER

Identifier Source: secondary_id

12183

Identifier Type: -

Identifier Source: org_study_id

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