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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1161-4956 | Registry Identifier | WHO |
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The purpose of this study is to evaluate the efficacy of vortioxetine (5, 10, and 20 mg) versus placebo during the first 28 weeks of the 32-week double-blind treatment period in the prevention of relapse in participants with MDD who responded to acute treatment with vortioxetine 10 mg.
The drug being tested in this study is called vortioxetine. Vortioxetine is being tested for the prevention of relapse in adults with major depressive disorder (MDD) who respond to daily treatment with vortioxetine. This study will look at relapse rates of MDD in people who take vortioxetine.
The study will enroll approximately 1100 participants. All participants will receive vortioxetine 10 mg open-label for the first 16 weeks of the study. Participants who meet the appropriate MDD response criteria from the Week 8 Visit through Week 16 Visit will be eligible for randomization into the double-blind treatment period. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):
All participants will be asked to take one capsule at the same time each day throughout the study.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 55 weeks. Participants will make 19 visits to the clinic, and will be contacted by telephone 4 weeks after last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open-label: Vortioxetine 10 mg | Experimental | Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period. |
|
| Double-blind: Placebo | Placebo Comparator | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
|
| Double-blind: Vortioxetine 5 mg | Experimental | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
|
| Double-blind: Vortioxetine 10 mg | Experimental | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vortioxetine | Drug | Vortioxetine capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time From Randomization to Relapse of Major Depressive Disorder During the First 28 Weeks of the 32-Week Double-Blind Treatment Period | Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored at date of withdrawal or date of Week 28 visit, whichever was earliest. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The inter-quartile range (IQR) was 25th percentile to 75th percentile. | From date of double-blind randomization (Week 16) up to relapse or first 28 weeks of Double-blind Period which occurs first (Up to Week 44) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher score indicates greater severity of symptoms. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. Mixed model for repeated measures (MMRM) was used for analyses. |
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Inclusion Criteria:
Exclusion Criteria:
Has received any investigational compound within 30 days prior to screening or 5 half-lives prior to screening, whichever is longer.
Has previously or is currently participating in this study.
Has participated in 2 or more clinical studies in the year prior to screening, or has participated in a clinical trial for a psychiatric condition that is exclusionary per this protocol.
Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
Has one or more of the following:
The current depressive symptoms of the participant are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
Has a history of lack of response to previous adequate treatment with vortioxetine for any MDD episode with adequate treatment considered to be known dose of vortioxetine in the approved recommended dose range for at least 6 weeks duration.
Has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
Has started receiving formal cognitive or behavioral therapy, systematic psychotherapy within 30 days from screening or plans to initiate such therapy during the study (supportive therapy, marital therapy and bereavement counseling are allowed).
Has a significant risk of suicide according to the investigator's clinical judgment or has a score ≥5 on item 10 (suicidal thoughts) of the MADRS or has made a suicide attempt in the previous 6 months.
Is required to take excluded medications or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study.
Has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, hematological, infectious, dermatological disorder or metabolic disturbance.
Note: For the purposes of this protocol fibromyalgia, obstructive sleep apnea, chronic pain diagnosis, and morbid obesity (BMI of > 40) are considered unstable due to the potential impact on assessment of the primary endpoint.
Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.
Has 1 or more laboratory value outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant; or the participant has any of the following values at the Screening Visit:
Has glycosylated hemoglobin (HbA1C) ≥7% at screening and no prior diagnosis of diabetes and/or treatment for diabetes. NOTE: Participants with known stable diabetes are not excluded.
Has a thyroid stimulating hormone (TSH) value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator. NOTE: Free T4 will be checked if TSH is out of range. If free T4 is abnormal the participant will be excluded.
Has clinically significant abnormal vital signs as determined by the investigator.
Has an abnormal electrocardiogram (ECG) as determined by the central reader and confirmed as clinically significant by the investigator.
Is positive for Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, or has a history of human immunodeficiency virus (HIV) infection.
Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability or efficacy.
The participant, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
Has a history of hypersensitivity or allergies to vortioxetine.
If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
The participant is considered to be treatment resistant, eg, the participant has not responded to adequate monotherapy treatments of at least 6 weeks' duration, or has only responded to combination or augmentation therapy.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NoesisPharma | Phoenix | Arizona | 85032 | United States | ||
| SW Biomedical Research, LLC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35131363 | Derived | Thase ME, Jacobsen PL, Hanson E, Xu R, Tolkoff M, Murthy NV. Vortioxetine 5, 10, and 20 mg significantly reduces the risk of relapse compared with placebo in patients with remitted major depressive disorder: The RESET study. J Affect Disord. 2022 Apr 15;303:123-130. doi: 10.1016/j.jad.2022.02.002. Epub 2022 Feb 5. |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants with diagnosis of major depressive disorder (MDD) were enrolled to receive vortioxetine 10 mg in the Open-label Period for up to 16 weeks. Responders (defined below) were randomized in 1:1:1:1 ratio to receive vortioxetine 5 mg, 10 mg or 20 mg or placebo for up to 32 weeks in the Double-blind Period.
Participants took part in the study at 74 investigative sites in the United States from 10 February 2015 to 25 April 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Open-label: Vortioxetine 10 mg | Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Open-label Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 12, 2019 | Apr 3, 2020 |
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| Double-blind: Vortioxetine 20 mg | Placebo Comparator | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
|
|
| Placebo | Drug | Vortioxetine placebo-matching capsules |
|
| Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 |
| Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed | The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participant who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness on the following scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. MMRM was used for analyses. | Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 |
| Clinical Global Impression Scale-Global Improvement Scale (CGI-I) Score | The CGI-I scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. | Week 32 |
| Time From Randomization to Relapse of Major Depressive Disorder During the Entire 32-Week Double-Blind Treatment Period | Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The IQR was 25th percentile to 75th percentile. | From date of double-blind randomization (Week 16) up to relapse or 32 weeks of Double-blind Period which occurs first (Up to Week 44) |
| Tucson |
| Arizona |
| 85712 |
| United States |
| CNS Research Science, Inc. | Cerritos | California | 90703 | United States |
| Collaborative Neuroscience Network, LLC | Garden Grove | California | 92845 | United States |
| Irvine Center for Clinical Research, Inc. | Irvine | California | 92614 | United States |
| Synergy Clinical Research of Escondido | Lemon Grove | California | 91945 | United States |
| Pharmacology Research Institute | Los Alamitos | California | 90720 | United States |
| Pacific Institute of Medical Research | Los Angeles | California | 90024 | United States |
| CNRI - Los Angeles, LLC | Pico Rivera | California | 90660 | United States |
| CNRI - San Diego, LLC | San Diego | California | 92102 | United States |
| Artemis Institute for Clinical Research, LLC | San Diego | California | 92103 | United States |
| University of California San Diego Medical Center | San Diego | California | 92103 | United States |
| Pasadena Research Institute | San Gabriel | California | 91776 | United States |
| Collaborative Neuroscience Network, LLC | Torrance | California | 90502 | United States |
| Research Center for Clinical Studies, Inc. | Norwalk | Connecticut | 06851 | United States |
| CNS Clinical Research Group | Coral Springs | Florida | 33067 | United States |
| Gulfcoast Medical Research Center, LLC | Fort Myers | Florida | 33912 | United States |
| MD Clinical | Hallandale | Florida | 33009 | United States |
| Indago Research & Health Center, Inc. | Hialeah | Florida | 33012 | United States |
| Clinical Neuroscience Solutions, Inc. | Jacksonville | Florida | 32256 | United States |
| Meridien Research | Maitland | Florida | 32751 | United States |
| Sarkis Clinical Trials - Parent | Ocala | Florida | 34474 | United States |
| Clinical Neuroscience Solutions, Inc. | Orlando | Florida | 32801 | United States |
| Stedman Clinical Trials, LLC | Tampa | Florida | 33613 | United States |
| Janice L. Miller, M.D., PA d/b/a Janus Center for Psychiatric Reseach | West Palm Beach | Florida | 33407 | United States |
| Radiant Research, Inc. | Atlanta | Georgia | 30328 | United States |
| Atlanta Center for Medical Research | Atlanta | Georgia | 30331 | United States |
| iResearch Atlanta, LLC | Decatur | Georgia | 30030 | United States |
| Alexian Brothers Center for Psychiatric Research | Arlington Heights | Illinois | 60005 | United States |
| Rush St Lukes Presbyterian Medical Center | Chicago | Illinois | 60612 | United States |
| Capstone Clinical Research, Inc. | Libertyville | Illinois | 60048 | United States |
| Goldpoint Clinical Research, LLC | Indianapolis | Indiana | 46260 | United States |
| Buynak Clinical Research | Valparaiso | Indiana | 46383 | United States |
| Phoenix Medical Research, Inc. | Prairie Village | Kansas | 66208 | United States |
| Heartland Research Associates, LLC | Wichita | Kansas | 67207 | United States |
| Lake Charles Clinical Trials, LLC | Lake Charles | Louisiana | 70629 | United States |
| Pharmasite Research, Inc. | Baltimore | Maryland | 21208 | United States |
| Potomac Grove Clinical Research Center | Gaithersburg | Maryland | 20877 | United States |
| Boston Clinical Trials & Medical Research | Boston | Massachusetts | 02131 | United States |
| Univ. of Massachussetts Memorial Health Care Systems | Worcester | Massachusetts | 01605-2610 | United States |
| Altea Research Institute | Las Vegas | Nevada | 89102 | United States |
| Hassman Research Institute | Berlin | New Jersey | 08009 | United States |
| Erie County Medical Center Corporation | Buffalo | New York | 14215 | United States |
| Neurobehavioral Research, Inc. | Cedarhurst | New York | 11516 | United States |
| CNS Research Science, Inc. | Jamaica | New York | 11432 | United States |
| Village Clinical Research, Inc. | New York | New York | 10003 | United States |
| Manhattan Behavioral Medicine, PLLC | New York | New York | 10022 | United States |
| Finger Lakes Clinical Research | Rochester | New York | 14618 | United States |
| Montefiore Medical Center PRIME | The Bronx | New York | 10467 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Clinical Trials of America, Inc | Hickory | North Carolina | 28601 | United States |
| NorthCoast Clinical Trials, Inc. | Beachwood | Ohio | 44122 | United States |
| Patient Priority Clinical Sites, LLC | Cincinnati | Ohio | 45215 | United States |
| IPS Research Company | Oklahoma City | Oklahoma | 73103 | United States |
| Cutting Edge Research Group, Inc. | Oklahoma City | Oklahoma | 73116 | United States |
| Summit Research Network (Oregon) Inc. | Portland | Oregon | 97210 | United States |
| Oregon Center for Clinical Investigations, Inc. | Portland | Oregon | 97214 | United States |
| Suburban Research Associates | Media | Pennsylvania | 19063 | United States |
| Keystone Clinical Studies, LLC | Norristown | Pennsylvania | 19403 | United States |
| University of Pennsylvania School of Medicine | Philadelphia | Pennsylvania | 19104 | United States |
| Lincoln Research | Lincoln | Rhode Island | 02865 | United States |
| Medical University of South Carolina (MUSC) | Charleston | South Carolina | 29401 | United States |
| Coastal Carolina Research Center, Inc | Mt. Pleasant | South Carolina | 29464 | United States |
| Clinical Neuroscience Solutions, Inc. | Memphis | Tennessee | 38119 | United States |
| FutureSearch Clinical Trials, L.P. | Austin | Texas | 78731 | United States |
| BioBehavioral Research of Austin | Austin | Texas | 78759 | United States |
| FutureSearch Trials of Dallas, LP | Dallas | Texas | 75231 | United States |
| Bayou City Research, Ltd. | Houston | Texas | 77007 | United States |
| Houston Clinical Trials, LLC | Houston | Texas | 77098 | United States |
| Pillar Clinical Research, LLC | Richardson | Texas | 75080 | United States |
| Clinical Trials of Texas, Inc. | San Antonio | Texas | 78229 | United States |
| Radiant Research, Inc. | Murray | Utah | 84123 | United States |
| Neuropsychiatric Associates | Woodstock | Vermont | 05091 | United States |
| University of Virginia Health System | Charlottesville | Virginia | 22903 | United States |
| Virginia Commonwealth University Medical Center | Richmond | Virginia | 23298-5054 | United States |
| Eastside Therapeutic Resource | Everett | Washington | 98201 | United States |
| Summit Research Network (Seattle), LLC | Seattle | Washington | 98104 | United States |
| Frontier Institute | Spokane | Washington | 99204 | United States |
| Northbrooke Research Center | Brown Deer | Wisconsin | 53223 | United States |
| FG001 | Double-blind: Placebo | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| FG002 | Double-blind: Vortioxetine 5 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| FG003 | Double-blind: Vortioxetine 10 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| FG004 | Double-blind: Vortioxetine 20 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| COMPLETED |
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| NOT COMPLETED |
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| Double-blind Period |
|
|
Safety Set for Open-label Period included all participant who received at least 1 dose of Open-label study medication. Baseline I is defined as the last non-missing observation prior to the first dose of open-label study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Open-label: Vortioxetine 10 mg | Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||||
| Height | Mean | Standard Deviation | cm |
| |||||||||||||||||
| Weight | Mean | Standard Deviation | kg |
| |||||||||||||||||
| Body Mass Index (BMI) | BMI=Weight (kg)/height (m^2) | Mean | Standard Deviation | kg/m^2 |
| ||||||||||||||||
| Smoking Classification | Count of Participants | Participants |
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| Alcohol Consumption | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time From Randomization to Relapse of Major Depressive Disorder During the First 28 Weeks of the 32-Week Double-Blind Treatment Period | Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored at date of withdrawal or date of Week 28 visit, whichever was earliest. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The inter-quartile range (IQR) was 25th percentile to 75th percentile. | Full Analysis Set (FAS) included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. | Posted | Median | Inter-Quartile Range | weeks | From date of double-blind randomization (Week 16) up to relapse or first 28 weeks of Double-blind Period which occurs first (Up to Week 44) |
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| Secondary | Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher score indicates greater severity of symptoms. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. Mixed model for repeated measures (MMRM) was used for analyses. | FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. Number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Least Squares Mean | Standard Error | scores on scale | Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 |
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| Secondary | Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed | The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participant who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness on the following scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. MMRM was used for analyses. | FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. Number analyzed is the number of participants with data available for analysis at the given time-point. | Posted | Least Squares Mean | Standard Error | scores on scale | Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 |
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| Secondary | Clinical Global Impression Scale-Global Improvement Scale (CGI-I) Score | The CGI-I scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. | FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. Overall number of participants analyzed is the number of participants with data available for analyses. | Posted | Mean | Standard Deviation | scores on scale | Week 32 |
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| Secondary | Time From Randomization to Relapse of Major Depressive Disorder During the Entire 32-Week Double-Blind Treatment Period | Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The IQR was 25th percentile to 75th percentile. | FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. | Posted | Median | Inter-Quartile Range | weeks | From date of double-blind randomization (Week 16) up to relapse or 32 weeks of Double-blind Period which occurs first (Up to Week 44) |
|
From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open-label: Vortioxetine 10 mg | Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period. | 0 | 1,106 | 9 | 1,106 | 417 | 1,106 |
| EG001 | Double-blind: Placebo | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. | 0 | 151 | 1 | 151 | 16 | 151 |
| EG002 | Double-blind: Vortioxetine 5 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. | 0 | 140 | 3 | 140 | 30 | 140 |
| EG003 | Double-blind: Vortioxetine 10 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. | 1 | 145 | 4 | 145 | 27 | 145 |
| EG004 | Double-blind: Vortioxetine 20 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. | 0 | 144 | 0 | 144 | 32 | 144 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure | Cardiac disorders | MedDRA: 22.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA: 22.0 | Systematic Assessment |
| |
| Post procedural cellulitis | Infections and infestations | MedDRA: 22.0 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA: 22.0 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA: 22.0 | Systematic Assessment |
| |
| Intraductal proliferative breast lesion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA: 22.0 | Systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA: 22.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with vortioxetine 10 mg and was not related. |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA: 22.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA: 22.0 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA: 22.0 | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA: 22.0 | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA: 22.0 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA: 22.0 | Systematic Assessment |
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| Abortion missed | Pregnancy, puerperium and perinatal conditions | MedDRA: 22.0 | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA: 22.0 | Systematic Assessment |
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| Panic attack | Psychiatric disorders | MedDRA: 22.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA: 22.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA: 22.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA: 22.0 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA: 22.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA: 22.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA: 22.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA: 22.0 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Sep 25, 2015 | Apr 3, 2020 | Prot_001.pdf |
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000078784 | Vortioxetine |
| ID | Term |
|---|---|
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Significant Protocol Deviation |
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| Noncompliance with Study Drug |
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| Lost to Follow-up |
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| Voluntary Withdrawal |
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| Relapse |
|
| Reason not Specified |
|
| Missing |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
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| Participant is an Ex-smoker |
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| Consumes Once a Week |
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| Consumes 2 to 6 Times per Week |
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| Consumes Daily |
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| Participant was an Ex-Drinker |
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| Double-blind Vortioxetine 10 mg Vs Double-blind Placebo | Cox Proportional Hazards Model | Cox proportional hazards model with a factor for treatment and baseline II MADRS total score as a covariate, using the exact method to handle ties. | 0.002 | Gate-keeping fixed-sequence testing procedure was used for multiple comparisons. | Hazard Ratio (HR) | 0.476 | 2-Sided | 95 | 0.296 | 0.767 | Superiority |
| Double-blind Vortioxetine 20 mg Vs Double-blind Placebo | Cox Proportional Hazards Model | Cox proportional hazards model with a factor for treatment and baseline II MADRS total score as a covariate, using the exact method to handle ties. | 0.003 | Gate-keeping fixed-sequence testing procedure was used for multiple comparisons. | Hazard Ratio (HR) | 0.483 | 2-Sided | 95 | 0.298 | 0.782 | Superiority |
| OG002 | Double-blind: Vortioxetine 10 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| OG003 | Double-blind: Vortioxetine 20 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
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|
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
| OG002 | Double-blind: Vortioxetine 10 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| OG003 | Double-blind: Vortioxetine 20 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
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|
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| OG003 | Double-blind: Vortioxetine 20 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
|
|
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| OG002 | Double-blind: Vortioxetine 10 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
| OG003 | Double-blind: Vortioxetine 20 mg | Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. |
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