NCT01187407|CompletedPhase 3ResultsDMC

A Study of Flexible or Fixed Dose LY2216684 as Adjunctive Treatment for Participants With Major Depressive Disorder Who Have Had a Partial Response to Selective Serotonin Reuptake Inhibitor (SSRI) Treatment

A Randomized, Placebo-Controlled, Double-Blind Study of LY2216684 Flexible-Dose 12 mg to 18 mg Once Daily and LY2216684 Fixed-Dose 6 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment

Eli Lilly and Company ClinicalTrials.gov

Compare

2 other identifiers

12182H9P-MC-LNBQ

Study Type

interventional

Target

1,480

Locations

7 countries

Sites

Timeline

RegisteredAug 2010

StartedMar 2011

CompletionAug 2013

Brief Summary

The purpose of this study is to assess if LY2216684 (flexible dose of 12 to 18 milligrams \[mg\] or fixed dose of 6 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

1,480

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Mar 2011

Geographic Reach

7 countries

54 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.4 years study duration

First Submitted

Initial submission to the registry

August 20, 2010

Completed

4 days until next milestone

First Posted

Study publicly available on registry

August 24, 2010

Completed

6 months until next milestone

Study Start

First participant enrolled

March 1, 2011

Completed

2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2013

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2013

Completed

4.7 years until next milestone

Results Posted

Study results publicly available

April 24, 2018

Completed

Last Updated

April 24, 2018

Status Verified

March 1, 2018

Enrollment Period

2.4 years

First QC Date

August 20, 2010

Results QC Date

February 17, 2018

Last Update Submit

March 25, 2018

Conditions

Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (1)

Change From Randomization to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS had a 10-item checklist (sadness \[apparent\], sadness \[reported\], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items were rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, investigator, visit, baseline score, treatment-by-visit, and baseline score-by-visit.
Randomization, 8 weeks

Secondary Outcomes (19)

Change From Randomization to Week 8 in the Sheehan Disability Scale (SDS) Global Functional Impairment Score
Randomization, 8 weeks
Change From Randomization to Week 8 in the Fatigue Associated With Depression (FAsD) Impact Subscale Score
Randomization, 8 weeks
Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 up to Week 8
Randomization up to 8 weeks
Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal 10 for at Least 2 Consecutive Measurements, Including the Participant's Last Measurement
Randomization up to 8 weeks
Change From Randomization to Week 8 in the Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score
Randomization, 8 weeks
+14 more secondary outcomes

Study Arms (3)

12 or 18 mg flexible dose LY2216684 + SSRI

EXPERIMENTAL

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 (orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to a 12 or 18 mg flexible dose of LY2216684. During the AT Phase, participants first received 6 mg LY2216684 QD for 3 days, followed by 12 mg QD for the next 11 days. Then, based on efficacy and tolerability, dosage could be increased to 18 mg QD over the next 6 weeks. Participants on 18 mg QD could have had their dose decreased back 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.

Drug: LY2216684Drug: PlaceboDrug: SSRI

6 mg fixed dose LY2216684 + SSRI

EXPERIMENTAL

LY2216684: fixed dose of 6 mg, administered orally, QD for 8 weeks, adjunctive to an SSRI Prior to entering the AT Phase, participants completed a 3-week CF Phase where they received placebo (orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to 6 mg fixed dose of LY2216684. During the AT Phase, participants received a 6 mg fixed dose of LY2216684 adjunctive to their SSRI for 8 weeks. Participants who completed the AT Phase or discontinued early had the option to enter the DC Phase. During the 1-week abrupt DC Phase, participants maintained their SSRI treatment.

Drug: LY2216684Drug: PlaceboDrug: SSRI

Placebo + SSRI

PLACEBO COMPARATOR

Placebo: administered orally, QD for 8 weeks, adjunctive to an SSRI Prior to entering the AT Phase, participants completed a 3-week CF Phase where they received placebo (orally, QD) adjunctive to their SSRI. After the CF Phase, and after randomization criteria were met, participants were randomized to placebo. 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 DC Phase. During the 1-week abrupt DC Phase, participants maintained their SSRI treatment.

Drug: PlaceboDrug: SSRI

Interventions

LY2216684DRUG

Also known as: Edivoxetine

12 or 18 mg flexible dose LY2216684 + SSRI6 mg fixed dose LY2216684 + SSRI

PlaceboDRUG

12 or 18 mg flexible dose LY2216684 + SSRI6 mg fixed dose LY2216684 + SSRIPlacebo + SSRI

SSRIDRUG

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

Also known as: selective serotonin reuptake inhibitor

12 or 18 mg flexible dose LY2216684 + SSRI6 mg fixed dose LY2216684 + SSRIPlacebo + SSRI

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Clinical diagnosis of Major Depressive Disorder (MDD)
Using a reliable method of birth control
Are taking a selective serotonin reuptake inhibitor (SSRI) approved for MDD treatment within the participant'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
Reliable and able to keep all scheduled appointments

You may not qualify if:

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 that could be exacerbated by noradrenergic agents, including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angle glaucoma, and history of 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 (VNS) transcranial magnetic stimulation (TMS), or psychosurgery
Have received electroconvulsive therapy (ECT) in the past year
Enrollment in a clinical study for an investigational drug
Serious or unstable medical condition
History of seizure disorders
+2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Eli Lilly and Companylead

Study Sites (54)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Birmingham, Alabama, 35216, United States

Location

Phoenix, Arizona, 85032, United States

Location

Chino, California, 91710, United States

Location

Glendale, California, 91204, United States

Location

Imperial, California, 92251, United States

Location

National City, California, 91950, United States

Location

Sherman Oaks, California, 91403, United States

Location

Colorado Springs, Colorado, 80907, United States

Location

Clearwater, Florida, 33761, United States

Location

Coral Gables, Florida, 33145, United States

Location

Fort Lauderdale, Florida, 33319, United States

Location

Tampa, Florida, 33613, United States

Location

Atlanta, Georgia, 30308, United States

Location

Hoffman Estates, Illinois, 60169, United States

Location

Indianapolis, Indiana, 46260, United States

Location

Prairie Village, Kansas, 66206, United States

Location

Wichita, Kansas, 67205, United States

Location

Baltimore, Maryland, 21285, United States

Location

Haverhill, Massachusetts, 01830, United States

Location

Weymouth, Massachusetts, 02190, United States

Location

Flowood, Mississippi, 39232, United States

Location

O'Fallon, Missouri, 63368, United States

Location

Brooklyn, New York, 11235, United States

Location

New York, New York, 10021, United States

Location

Beachwood, Ohio, 44122, United States

Location

Oklahoma City, Oklahoma, 73103, United States

Location

Philadelphia, Pennsylvania, 19107, United States

Location

Houston, Texas, 77096, United States

Location

Rab, 51280, Croatia

Location

Zagreb, 10090, Croatia

Location

Hořovice, 268 31, Czechia

Location

Hostivice, 25201, Czechia

Location

Kladno, 27201, Czechia

Location

Olomouc, 77900, Czechia

Location

Prague, 100 00, Czechia

Location

Strakonice, 38601, Czechia

Location

Ústí nad Labem, 400001, Czechia

Location

Helsinki, 00100, Finland

Location

Joensuu, 80100, Finland

Location

Kuopio, 70110, Finland

Location

Tampere, 33200, Finland

Location

Turku, 20100, Finland

Location

Chiba, 270-0014, Japan

Location

Fukuoka, 810-0035, Japan

Location

Fukushima, 961-0021, Japan

Location

Hyōgo, 661-0002, Japan

Location

Kanagawa, 247-0056, Japan

Location

Tokyo, 100-0006, Japan

Location

San Juan, 00918, Puerto Rico

Location

Bratislava, 85101, Slovakia

Location

Košice, 04001, Slovakia

Location

Michalovce, SK-071 01, Slovakia

Location

Rimavská Sobota, 97901, Slovakia

Location

Rožňava, 04801, Slovakia

Location

Related Publications (2)

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.
PMID: 27685842DERIVED
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.
PMID: 27035159DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanolSelective Serotonin Reuptake Inhibitors

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake InhibitorsMembrane Transport ModulatorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesNeurotransmitter AgentsSerotonin AgentsPhysiological Effects of Drugs

Results Point of Contact

Title: Chief Medical Officer
Organization: Eli Lilly and Company

Study Officials

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)
Eli Lilly and Company
STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee: No
Restriction Type: GT60
Restrictive Agreement: Yes

Study Design

Study Type: interventional
Phase: phase 3
Allocation: RANDOMIZED
Masking: QUADRUPLE
Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose: TREATMENT
Intervention Model: PARALLEL
Sponsor Type: INDUSTRY
Responsible Party: SPONSOR

Study Record Dates

First Submitted

August 20, 2010

First Posted

August 24, 2010

Study Start

March 1, 2011

Primary Completion

August 1, 2013

Study Completion

August 1, 2013

Last Updated

April 24, 2018

Results First Posted

April 24, 2018

Record last verified: 2018-03

Locations

CZ(7)SL(5)CR(2)JP(6)US(28)PR(1)FI(5)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Results Posted

Conditions

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (19)

Study Arms (3)

12 or 18 mg flexible dose LY2216684 + SSRI

6 mg fixed dose LY2216684 + SSRI

Placebo + SSRI

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (54)

Related Publications (2)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Results Point of Contact

Study Officials

Publication Agreements

Study Design

Study Record Dates

Locations