Clinical trial NCT00840034: A Study of Adjunctive Treatment to Antidepressant Therapy for Adults With Major Depressive Disorder
Official title: A Study of Augmentation With LY2216684 for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-02-10
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose is to study the efficacy, safety, and tolerability of LY2216684 as an adjunctive treatment for 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) (as defined by history).

Detailed description: This is a 12 week multi-center, double-blind, placebo-controlled study on the efficacy of LY2216684 augmentation of selective serotonin reuptake inhibitors (SSRIs) in participants with MDD who have a partial response to treatment with an SSRI. While remaining on a steady dose of their SSRI treatment at entry into the study, participants will be randomly assigned to adjunctive treatment with LY2216684 or placebo in a 1:1 ratio for 10 weeks of acute treatment.

Eligibility criteria: Inclusion Criteria:

* 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 to an adequate course of treatment defined by the investigator's opinion that participant had attained at least minimal improvement on their current Selective serotonin reuptake inhibitor (SSRI) treatment
* Women of child-bearing potential must test negative for pregnancy and agree to use a reliable method of birth control
* Grid Hamilton Rating Scale for Depression (GRID-HAMD17) total score greater than or equal 16 to at both study entry and study enrollment
* SSRI treatment for at least 6 weeks at a stable dose for at least 2 weeks prior to study enrollment
* Stated participant preference for augmentation rather than switching antidepressant treatment

Exclusion Criteria:

* Are currently involved in or discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug
* Have previously completed or withdrawn from this study or any other study investigating LY2216684
* Have had or currently have any additional ongoing DSM-IV-TR Axis 1 condition other than MDD
* Have had any anxiety disorder preceding the onset of depression that was considered the primary diagnosis within 1 year of study entry
* Have a current or previous diagnosis of Bipolar I or II, psychotic depression, schizophrenia or other psychotic disorder
* Have a history of substance abuse within the past 1 year
* Have an Axis II disorder which, in the judgment of the investigator, would interfere with compliance with the protocol
* Have had a 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 history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or psychosurgery within the last year
* Women who are pregnant or breastfeeding
* Participants who are judged to be at serious risk for harm to self or others
* Have a serious or unstable medical illness
* Have any diagnosed medical condition which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia or tachyarrhythmia, narrow angle glaucoma, or urinary hesitation or retention
* Have a history of severe allergies to more than 1 class of medication or multiple adverse drug reactions
* Have a history of any seizure disorder (other than febrile seizures)
* Are taking noradrenergic psychotropic medications, such as tricyclic antidepressants or serotonin norepinephrine reuptake inhibitors (SNRI)
* Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to study entry
* Require psychotropic medication other than sedative/hypnotic medication for sleep
* Are taking or have received treatment with any excluded medication within 7 days prior to study enrollment
* Have a thyroid stimulating hormone (TSH ) level outside the established reference range
* Have initiate or discontinued hormone therapy within the previous 3 months prior to enrollment
* Initiation or change in intensity of psychotherapy or other non-drug therapies within 6 weeks prior to enrollment
* A positive urine drug screen for any substance of abuse at study entry

Primary outcomes:
measure: Change From Baseline to 8 Weeks in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Baseline, 8 weeks
Secondary outcomes:
measure: Change From Baseline to 8 Weeks in 16-Item Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) Total Score
timeFrame: Baseline, 8 weeks
measure: Change From Baseline to 8 Weeks in 16-Item Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) Individual Items
timeFrame: Baseline, 8 weeks
measure: Change From Baseline to 8 Weeks in Hospital Anxiety and Depression Scale (HADS)
timeFrame: Baseline, up to 8 weeks
measure: Change From Baseline to 8 Weeks in Clinical Global Impression of Severity (CGI-S)
timeFrame: Baseline, 8 weeks
measure: Change From Baseline to 8 Weeks in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
timeFrame: Baseline, 8 weeks
measure: Change From Baseline to 8 Weeks in Fatigue Associated With Depression Participant-Reported Outcome (FAsD PRO)
timeFrame: Baseline, up to 8 weeks
measure: Change From Baseline to 8 Weeks in Visual Analog Scale for Fatigue (VAS-F)
timeFrame: Baseline, up to 8 weeks
measure: Change From Baseline to 8 Weeks in Visual Analog Scale for Pain (VAS-P)
timeFrame: Baseline, up to 8 weeks
measure: Change From Baseline to 8 Weeks in Sheehan Disability Scale (SDS)
timeFrame: Baseline, up to 8 weeks
measure: Change From Baseline to 8 Weeks in Quality of Life Enjoyment and Satisfaction Survey-Short Form (Q-LES-Q-SF)
timeFrame: Baseline, up to 8 weeks
measure: Change From Baseline to 8 Weeks Massachusetts General Hospital Sexual Functioning Questionnaire (MGH-SFQ)
timeFrame: Baseline, up to 8 weeks
measure: Colombia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, 8 weeks
Other outcomes:
measure: Change From Baseline to 8 Weeks in Supine Systolic and Diastolic Blood Pressure
timeFrame: Baseline, 8 weeks
measure: Change From Baseline to 8 Weeks in Supine Pulse
timeFrame: Baseline, 8 weeks
Locations:
city: Birmingham
country: United States
facility: 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.
state: Alabama
city: Little Rock
country: United States
facility: 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.
state: Arkansas
city: Carson
country: United States
facility: 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.
state: California
city: Costa Mesa
country: United States
facility: 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.
state: California
city: Santa Ana
country: United States
facility: 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.
state: California
city: Torrance
country: United States
facility: 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.
state: California
city: Denver
country: United States
facility: 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.
state: Colorado
city: Coral Springs
country: United States
facility: 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.
state: Florida
city: Jacksonville
country: United States
facility: 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.
state: Florida
city: Miami
country: United States
facility: 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.
state: Florida
city: Orlando
country: United States
facility: 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.
state: Florida
city: Smyrna
country: United States
facility: 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.
state: Georgia
city: Oak Brook
country: United States
facility: 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.
state: Illinois
city: Lafayette
country: United States
facility: 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.
state: Indiana
city: Baltimore
country: United States
facility: 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.
state: Maryland
city: Saint Charles
country: United States
facility: 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.
state: Missouri
city: Willingboro
country: United States
facility: 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.
state: New Jersey
city: Albuquerque
country: United States
facility: 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.
state: New Mexico
city: Fresh Meadows
country: United States
facility: 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.
state: New York
city: Rochester
country: United States
facility: 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.
state: New York
city: Philadelphia
country: United States
facility: 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.
state: Pennsylvania
city: Austin
country: United States
facility: 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.
state: Texas
city: Dallas
country: United States
facility: 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.
state: Texas
city: San Antonio
country: United States
facility: 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.
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.