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

NCT ID: NCT01173601

Last Updated: 2018-04-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1416 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2013-10-31

Brief Summary

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The primary purpose of this study is to assess whether at least 1 dose of LY2216684 (12 milligrams \[mg\] or 18 mg once daily) is superior to placebo once daily in the adjunctive treatment of participants 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 8-week, double-blind, acute adjunctive treatment phase.

Detailed Description

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Following the Confirmation Phase, participants were randomized to adjunctive LY2216684 or adjunctive placebo if they met the following randomization criteria: 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

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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12 milligrams (mg) LY2216684 + SSRI

LY2216684: 12 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 12-mg treatment arm (AT Phase).

Participants who completed the AT Phase or discontinued early entered a 2-week Discontinuation (DC) Phase. Participants were randomly assigned to either abrupt DC or tapered DC over the 2-week DC Phase. Participants maintained their SSRI treatment during the DC Phase.

Group Type EXPERIMENTAL

LY2216684

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.

18 milligrams (mg) LY2216684 + SSRI

LY2216684: 12 milligrams (mg), administered orally, once daily (QD) for 1 week, followed by 18 mg, administered orally, once daily for 7 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 18-mg treatment arm (AT Phase).

Participants who completed the AT Phase or discontinued early entered a 2-week Discontinuation (DC) Phase. Participants were randomly assigned to either abrupt DC or tapered DC over the 2-week DC Phase. Participants maintained their SSRI treatment during the DC Phase.

Group Type EXPERIMENTAL

LY2216684

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: Tablet equivalent to LY2216684, administered orally, once daily (QD) for 11 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 (AT Phase).

Participants who completed the AT Phase or discontinued early had the option to enter the Discontinuation (DC) Phase. Participants who had received placebo were assigned to the abrupt DC over the 2-week DC Phase. Participants maintained their SSRI treatment during the DC Phase.

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

* 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 a selective serotonin reuptake inhibitor (SSRI) approved for MDD treatment within the participant's country. 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 a DSM-IV-TR Axis II disorder that, in the judgment of the investigator, would interfere with compliance with protocol
* Have any diagnosed medical condition that 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
* 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, 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 non-drug therapies (such as acupuncture or hypnosis) within 12 weeks prior to enrollment or any time during the study. Have no change in intensity of psychotherapy within the last 6 weeks prior to enrollment or at any time during the study.
* Participants who, in the opinion of the investigator, are judged to be at serious risk for harm to self or others
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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Irvine, California, United States

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La Habra, California, United States

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Redlands, California, United States

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Denver, Colorado, United States

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Jacksonville, Florida, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Baltimore, Maryland, United States

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St Louis, Missouri, United States

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Berlin, New Jersey, United States

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Jamaica, New York, United States

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New York, New York, United States

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Dayton, Ohio, United States

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Middleburg Heights, Ohio, United States

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Allentown, Pennsylvania, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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San Antonio, Texas, United States

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Sugar Land, Texas, United States

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Murray, Utah, United States

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Milwaukee, Wisconsin, United States

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Fukuoka, , Japan

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Fukushima, , Japan

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Hyōgo, , Japan

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Kanagawa, , Japan

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Nagano, , Japan

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Saga, , Japan

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Tokyo, , Japan

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Daugavpils, , Latvia

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Jelgava, , Latvia

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Liepāja, , Latvia

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Sigulda, , Latvia

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Strenči, , Latvia

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?Uromin, , Poland

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Chełmno, , Poland

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Gdansk, , Poland

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Gorlice, , Poland

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Katowice, , Poland

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Leszno, , Poland

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Lublin, , Poland

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Tuszyn, , Poland

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Moscow, , Russia

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Rostov-on-Don, , Russia

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Yekaterinburg, , Russia

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Bellville, , South Africa

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Cape Town, , South Africa

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Centurion, , South Africa

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George, , South Africa

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West Cape, , South Africa

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Chernihiv District, , Ukraine

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Dnipropetrovsk, , Ukraine

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Donetsk, , Ukraine

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Kherson, , Ukraine

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Kyiv, , Ukraine

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Luhansk, , Ukraine

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Odesa, , Ukraine

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Poltava, , Ukraine

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Simferopol, , Ukraine

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Uzhhorod, , Ukraine

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Vinnytsia, , Ukraine

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Countries

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United States Japan Latvia Poland Russia South Africa Ukraine

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-LNBM

Identifier Type: OTHER

Identifier Source: secondary_id

11316

Identifier Type: -

Identifier Source: org_study_id

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