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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01185340




Registration number
NCT01185340
Ethics application status
Date submitted
18/08/2010
Date registered
19/08/2010
Date last updated
27/04/2018

Titles & IDs
Public title
A Study in Participants With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor
Scientific title
A Randomized Placebo-Controlled, Double-Blind Study of LY2216684 Flexible-Dose 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment
Secondary ID [1] 0 0
H9P-MC-LNBR
Secondary ID [2] 0 0
12183
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SSRI

Experimental: 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.

Placebo comparator: 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.


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Timepoint [1] 0 0
Randomization, 8 weeks
Secondary outcome [1] 0 0
Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Global Functional Impairment Score
Timepoint [1] 0 0
Randomization, 8 weeks
Secondary outcome [2] 0 0
Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Impact Subscale Score
Timepoint [2] 0 0
Randomization, 8 weeks
Secondary outcome [3] 0 0
Probability of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 at Week 8
Timepoint [3] 0 0
8 weeks
Secondary outcome [4] 0 0
Percentage of Participants Achieving a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of Less Than or Equal to 10 for at Least 2 Consecutive Measurements, Including the Participant's Last Measurement
Timepoint [4] 0 0
Randomization up to 8 weeks
Secondary outcome [5] 0 0
Change From Randomization to Week 8 in Hospital and Anxiety and Depression Scale (HADS) Anxiety Subscale Score
Timepoint [5] 0 0
Randomization, 8 weeks
Secondary outcome [6] 0 0
Probability of Participants Who Have a Greater Than or Equal to 50 Percent Improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 8
Timepoint [6] 0 0
8 weeks
Secondary outcome [7] 0 0
Change From Randomization to Week 8 in The Hospital Anxiety and Depression Scale (HADS) Depression Subscale Score
Timepoint [7] 0 0
Randomization, 8 weeks
Secondary outcome [8] 0 0
Change From Randomization to Week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) Individual Items
Timepoint [8] 0 0
Randomization, 8 weeks
Secondary outcome [9] 0 0
Change From Randomization to Week 8 in Clinical Global Impressions of Severity (CGI-S)
Timepoint [9] 0 0
Randomization, 8 weeks
Secondary outcome [10] 0 0
Change From Randomization to Week 8 in Fatigue Associated With Depression (FAsD) Average Score and Experience Subscale Score
Timepoint [10] 0 0
Randomization, 8 weeks
Secondary outcome [11] 0 0
Change From Randomization to Week 8 in Sheehan Disability Scale (SDS) Items
Timepoint [11] 0 0
Randomization, 8 weeks
Secondary outcome [12] 0 0
Change From Randomization to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)
Timepoint [12] 0 0
Randomization, 8 weeks
Secondary outcome [13] 0 0
Change From Randomization to Week 8 in the EuroQol Questionnaire-5 Dimension (EQ-5D)
Timepoint [13] 0 0
Randomization, 8 weeks
Secondary outcome [14] 0 0
Percentage of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
Timepoint [14] 0 0
Randomization up to 8 weeks
Secondary outcome [15] 0 0
Change From Randomization to Week 8 in Arizona Sexual Experiences (ASEX) Scale
Timepoint [15] 0 0
Randomization, 8 weeks
Secondary outcome [16] 0 0
Change From Randomization to Week 8 in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
Timepoint [16] 0 0
Randomization, 8 weeks
Secondary outcome [17] 0 0
Change From Randomization to Week 8 in Blood Pressure
Timepoint [17] 0 0
Randomization, 8 weeks
Secondary outcome [18] 0 0
Change From Randomization to Week 8 in Pulse Rate
Timepoint [18] 0 0
Randomization, 8 weeks

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2013
Sample size
Target
Accrual to date
Final
1056
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
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. - Everton Park
Recruitment hospital [2] 0 0
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. - Spring Hill
Recruitment hospital [3] 0 0
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. - Frankston
Recruitment hospital [4] 0 0
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. - Heidelberg
Recruitment hospital [5] 0 0
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. - Malvern
Recruitment hospital [6] 0 0
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. - Melbourne
Recruitment postcode(s) [1] 0 0
4053 - Everton Park
Recruitment postcode(s) [2] 0 0
4000 - Spring Hill
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3144 - Malvern
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Austria
State/province [11] 0 0
Vienna
Country [12] 0 0
Belgium
State/province [12] 0 0
Diest
Country [13] 0 0
Belgium
State/province [13] 0 0
Liège
Country [14] 0 0
Belgium
State/province [14] 0 0
Mont-Godinne
Country [15] 0 0
Germany
State/province [15] 0 0
Bad Saarow
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Bochum
Country [18] 0 0
Germany
State/province [18] 0 0
Cham
Country [19] 0 0
Germany
State/province [19] 0 0
Dresden
Country [20] 0 0
Germany
State/province [20] 0 0
Hattingen
Country [21] 0 0
Germany
State/province [21] 0 0
Leipzig
Country [22] 0 0
Germany
State/province [22] 0 0
Munich
Country [23] 0 0
Germany
State/province [23] 0 0
Nürnberg
Country [24] 0 0
Germany
State/province [24] 0 0
Prien
Country [25] 0 0
Germany
State/province [25] 0 0
Schwerin
Country [26] 0 0
Sweden
State/province [26] 0 0
Goteborg
Country [27] 0 0
Sweden
State/province [27] 0 0
Lund
Country [28] 0 0
Sweden
State/province [28] 0 0
Malmo
Country [29] 0 0
Sweden
State/province [29] 0 0
Solna
Country [30] 0 0
Sweden
State/province [30] 0 0
Stockholm
Country [31] 0 0
United Kingdom
State/province [31] 0 0
East Sussex
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Scotland
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Chesterfield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01185340
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01185340