Phase 3
N=1,249
A Study in Prevention of Re-emergence of Depression Symptoms
Major Depressive Disorder
Bottom Line
View on ClinicalTrials.gov: NCT01299272 ↗Enrolled (actual)
1,249
Serious AEs
1.5%
Results posted
Apr 2018
Primary outcome: Primary: Percentage of Participants Who Meet Criteria for Re-emergence of Depressive Symptoms Estimated by Kaplan-Meier Product Limit Method (Double-blind Randomized Withdrawal Period) — 10.43; 8.24 percentage of participants — p=0.485
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- LY2216684 (Drug); Placebo (Drug); SSRI (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Eli Lilly and Company
- Primary completion
- Nov 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Meet Criteria for Re-emergence of Depressive Symptoms Estimated by Kaplan-Meier Product Limit Method (Double-blind Randomized Withdrawal Period) |
10.43; 8.24 | 0.485 |
| SECONDARY Percentage of Participants With Re-emergence of Depressive Symptoms (Double-blind Randomized Withdrawal Period) |
9.9; 8.2 | — |
| SECONDARY Change From Randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores at Week 44 (Double-blind Randomized Withdrawal Period) |
0.40; 0.34; 0.09; 0.08; 0.09; 0.05 | — |
| SECONDARY Change From Randomization in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores at Week 44 (Double-blind Randomized Withdrawal Period) |
-0.00; 0.15; -0.18; 0.15 | — |
| SECONDARY Change From Randomization in the Clinical Global Impression of Severity (CGI-S) Scores at Week 44 (Double-blind Randomized Withdrawal Period) |
0.01; -0.00 | — |
| SECONDARY Change From Randomization in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score at Week 44 (Double-blind Randomized Withdrawal Period) |
-0.05; 0.05; -0.06; -0.01; -0.05; 0.02 | — |
| SECONDARY Change From Randomization in the Sheehan Disability Scale (SDS) Items at Week 44 (Double-blind Randomized Withdrawal Period) |
-0.24; 0.02; -0.17; -0.15; -0.26; -0.08 | — |
| SECONDARY Change From Randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 44 (Double-blind Randomized Withdrawal Period) |
0.01; 0.01; 0.01; 0.01; 1.87; 0.61 | — |
| SECONDARY Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Double-blind Randomized Withdrawal Period) |
5; 4; 1; 0 | — |
| SECONDARY Change From Randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (Double-blind Randomized Withdrawal Period) |
-0.39; -0.08 | — |
| SECONDARY Change From Randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 44 (Double-blind Randomized Withdrawal Period) |
-0.27; -0.05 | — |
| SECONDARY Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 8 (Acute Open-label Period) |
-13.21; -1.82; -1.86; -1.24; -1.29; -0.65 | — |
| SECONDARY Change From Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Individual Item Scores up to Week 20 (Stabilization Open-label Period) |
-0.38; -0.01; -0.08; -0.05; -0.12; 0.00 | — |
| SECONDARY Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 8 (Acute Open-label Period) |
-3.02; -3.98 | — |
| SECONDARY Change From Week 8 in the Hospital Anxiety and Depression Scale (HADS) Depression and Anxiety Subscale Scores up to Week 20 (Stabilization Open-label Period) |
-0.77; -0.74 | — |
| SECONDARY Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 8 (Acute Open-label Period) |
-1.51 | — |
| SECONDARY Change From Week 8 in the Clinical Global Impression of Severity (CGI-S) Scores up to Week 20 (Stabilization Open-label Period) |
-0.25 | — |
| SECONDARY Change From Baseline in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 8 (Acute Open-label Period) |
-0.82; -0.88; -0.85 | — |
| SECONDARY Change From Week 8 in the Fatigue Associated With Depression (FAsD) Average Score, Experience Subscale Score, and Impact Subscale Score up to Week 20 (Stabilization Open-label Period) |
-0.22; -0.15; -0.19 | — |
| SECONDARY Change From Baseline in the Sheehan Disability Scale (SDS) Items up to Week 8 (Acute Open-label Period) |
-2.17; -2.38; -2.16 | — |
| SECONDARY Change From Week 8 in the Sheehan Disability Scale (SDS) Items up to Week 20 (Stabilization Open-label Period) |
-0.58; -0.47; -0.50 | — |
| SECONDARY Change From Baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) Index Scores, Visual Analog Scale up to Week 20 (Open-label Period) |
0.15; 0.21; 18.07 | — |
| SECONDARY Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (Open-label Period) |
66; 5 | — |
| SECONDARY Change From Baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (Open-label Period) |
-1.78 | — |
| SECONDARY Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score at Week 20 (Open-label Period) |
-6.68 | — |
| SECONDARY Change From Randomization in Blood Pressure at Week 44 (Double-blind Randomized Withdrawal Period) |
-0.20; -4.19; 0.24; -4.18 | — |
| SECONDARY Change From Baseline in Blood Pressure up to Week 20 (Open-label Period) |
2.30; 2.81 | — |
| SECONDARY Change From Randomization in Pulse Rate at Week 44 (Double-blind Randomized Withdrawal Period) |
-2.54; -10.76 | — |
| SECONDARY Change From Baseline in Pulse Rate up to Week 20 (Open-label Period) |
10.80 | — |
Summary
The primary objective of this study was to assess the maintenance of efficacy of LY2216684 compared with placebo as adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs) as measured by the time-to-symptom reemergence among participants with major depressive disorder (MDD) who met randomization criteria with adjunctive LY2216684 during the stabilization period.
This trial consists of two distinct periods: an open-label treatment period, which consists of two parts, 8 weeks acute open-label with movement to 12 weeks open-label stabilization if participants are in remission at end of 8 weeks (open-label for 20 weeks total) followed by a randomized, double-blind, placebo-controlled period for 24 weeks.
Eligibility Criteria
Inclusion Criteria
- Outpatients with 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
- 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
- Have had at least 1 previous episode of MDD prior to the current episode within the past 5 years
Exclusion Criteria
- 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 a current or any 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 which could be exacerbated by noradrenergic agents, including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angle glaucoma, or history of urinary hesitation or retention
- Have initiated or discontinued hormone therapy (including birth control or thyroid hormone) within the previous 3 months prior to enrollment
- Have a lifetime history of vagal nerve stimulation (VNS), transcranial magnetic stimulation (TMS), or psychosurgery
- Have received electroconvulsive therapy (ECT) in the past year
- Have a serious or unstable medical condition
- Have a history of seizure disorders
- Have initiated psychotherapy, change in intensity of psychotherapy or other nondrug therapies (such as acupuncture or hypnosis) within 6 weeks prior to enrollment or 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
- Are pregnant or breastfeeding
- Meet criteria for treatment-resistant depression
Data sourced from ClinicalTrials.gov (NCT01299272). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.