Goal Achievement After a Change to Vortioxetine in Adults With Major Depressive Disorder

An Open-Label, Single-Arm, Multicenter, Prospective, Phase 4, Interventional, Flexible Dose Study to Evaluate the Effectiveness of Vortioxetine on Goal Achievement After a Change in Antidepressant Medication for the Treatment of Subjects With Major Depressive Disorder

The purpose of this study is to determine the effectiveness of treatment with vortioxetine on participant goal achievement after a change in antidepressant medication for the treatment of major depressive disorder (MDD).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Vortioxetine

Detailed Description

The drug being tested in this study is called Vortioxetine. Vortioxetine is being tested to treat depression in people who have major depressive disorder. This study will look at effectiveness of treatment with vortioxetine in participant's goal achievement for the treatment of major depressive disorder.

The study enrolled 123 patients. Participants will receive:

• Vortioxetine 10 to 20 mg

All participants will be asked to take one tablet at the same time each day throughout the study. The participants will receive a starting dose of 10 mg. The dose may be up-titrated to 20 mg. The dose may then be decreased by 5 mg based on participant's response and tolerability to higher dose as judged by the Investigator.

This multi-center trial will be conducted in Unites States. The overall time to participate in this study is 19 weeks. Participants will make multiple visits to the clinic and will be contacted by telephone for 4 weeks after last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Culver City, California, United States, 90230
      • Proscience Research Group
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC
    • Oakland, California, United States, 94607
      • Pacific Research Partners
    • Oceanside, California, United States, 92056
      • Excell Research
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
    • Upland, California, United States, 91207
      • University Medical Group
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers, LLC
  • Florida
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research Inc.
    • North Miami, Florida, United States, 33162
      • Behavioral Clinical Research , Inc
    • Orlando, Florida, United States, 32806
      • Compass Research Main
    • Tampa, Florida, United States, 33613
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
    • Naperville, Illinois, United States, 60563
      • Baber Research Group
  • Indiana
    • Evansville, Indiana, United States, 47713-1227
      • Deaconess Clinic
  • Massachusetts
    • New Bedford, Massachusetts, United States, 2740
      • Novex Clinical Research, LLC
    • South Weymouth, Massachusetts, United States, 2190
      • Coastal Research Associates, Inc.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan, Ann Arbor
  • New York
    • New York, New York, United States, 10023
      • Columbia University Medical Center
  • Ohio
    • Dayton, Ohio, United States, 45406
      • Dayton Clinical Research
  • Pennsylvania
    • Lansdale, Pennsylvania, United States, 19446
      • Green & Seidner Family Practice Associates
  • Texas
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA
    • San Antonio, Texas, United States, 78229
      • Radiant Research, Inc.
    • The Woodlands, Texas, United States, 77381
      • Family Psychiatry of The Woodlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Is suffering from Major Depressive Disorder (MDD) as the primary psychiatric diagnosis.
2. Has been or is currently being treated with an approved antidepressant (monotherapy) for 6 weeks or longer at an adequate therapeutic dose. Participants currently on an antidepressant at Screening will be discontinued in a manner that is consistent with labeling recommendations and conventional medical practice.
3. The antidepressant treatment must be on-going at time of Screening or have been discontinued within the 6 weeks prior to Screening.
4. Is considered appropriate for a change in antidepressant medication based on Investigator judgment in collaboration with the participant.
5. Has scores on Patient Health Questionnaire (PHQ-9) ≥5 and Clinical Global Impression Scale Severity (CGI-S ≥4).

Exclusion Criteria:

1. Has discontinued prior antidepressant treatment greater than 6 weeks from Screening.
2. Is considered to be at imminent risk for hospitalization due to severe depression in the opinion of the investigator. Recent hospitalization due to MDD within 3 months prior to Screening is exclusionary also.
3. Has a significant risk of suicide according to the Investigator's clinical judgment or has made an actual suicide attempt in the previous 6 months prior to Screening or scores "yes" on items 4 or 5 in the past 6 months on the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS).
4. Is considered to be treatment resistant, defined as participants with MDD who have not responded to 2 or more separate different antidepressant monotherapy trials of adequate dose and duration (6 weeks or longer) in their current episode. History of only responding to combination or augmentation therapy in previous major depressive episode (MDEs) is also considered evidence of treatment resistant depression.

5. Has 1 or more of the following:

   1. Current or history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including schizoaffective disorder, major depression with psychotic features, bipolar depression with psychotic features, obsessive compulsive disorder, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as determined by the investigator.
   2. Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine). The participants must have a negative urine drug screen (UDS) at Screening and Baseline, this includes benzodiazepines and opiates (including oxycodone) for which there is no prescription.
   3. Presence or history of a clinically significant neurological disorder (including epilepsy) as determined by the investigator.
   4. Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
6. Has a known history of acute narrow-angle glaucoma or is at risk of acute narrow-angle glaucoma.
7. Has a known unstable thyroid disorder or a thyroid-stimulating hormone value outside the normal range based on medical history that is deemed clinically significant by the investigator.
8. Has active hepatitis B or a known history of hepatitis C virus.
9. Has a known history of human immunodeficiency virus infection.
10. Has a history of gastric bypass.
11. Has previously or is currently participating in this study or another vortioxetine or LuAA21004 study.
12. Is receiving or who have started receiving formal cognitive or behavioral therapy, systematic psychotherapy within 30 days from screening or plan to initiate such therapy during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vortioxetine 10-20 mg; Vortioxetine 10 mg, tablets, orally, once daily followed by a dose adjustment to a maximum of 20 mg, tablets, orally, once daily up to 12 weeks. The dose may be decreased by 5 mg based on participant's response and tolerability as judged by the investigator.	Drug: Vortioxetine; Vortioxetine tablet; Other Names: LuAA21004

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Goal Attainment Scale (GAS) Score of ≥50 at Week 12	GAS is a tool to measure progress each participant has towards achieving their individualized goals. The standardized scoring was applied for statistical analysis. A semi-structured interview was conducted with each participant to conduct goal-setting at the outset of study. Another evaluation took place at end of study (EOS) visit to determine the level of progress at that time. The score for each goal ranged from -2 (much worse) to +2 (much better). GAS yielded a norm-based score standardized to a mean of 50 with a standard deviation (SD) of 10. Higher score indicates composite of 3 goals (50 or above) as response.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Goal Attainment Scale Score at Weeks 6 and 12	GAS is a tool to measure progress each participant has towards achieving their individualized goals. The standardized scoring was applied for statistical analysis. A semi-structured interview was conducted with each participant to conduct goal-setting at outset of study. Another evaluation took place at EOS visit to determine level of progress at that time. The score for each goal ranged from -2 (much worse) to +2 (much better). GAS yielded a norm-based score standardized to a mean of 50 with SD of 10. The total score ranges between 22.6 and 77.4. A positive change from baseline in the composite of 3 goals (50 or above) indicates response.	Baseline and Weeks 6 and 12
Change From Baseline in Patient Health Questionnaire (PHQ-9) Score at Weeks 6 and 12	PHQ-9 is a well-established participant reported outcome tool for assessment of change in depressive symptoms and is a sensitive measure of depression severity. The PHQ-9 consists of a 9-item scale originally developed for primary care settings, with 1 item corresponding to each of the 9 made symptom criteria for depression in diagnostic and statistical manual of mental disorders (DSM), asking if they have bothered the participant over the last 2 weeks. Each question is rated on a scale from 0 (not at all) to 3 (nearly every day). If any problems are answered 1 or higher, a final question on how difficult those problems made it to do work, take care of things at home, or get along with other people is completed, rated from not difficult at all to extremely difficult. The 9 questions are summed to a total score ranging from 0 to 27 with higher scores reflecting greater severity. A positive change from baseline indicates severe condition.	Baseline and Weeks 6 and 12
Change From Baseline in Perceived Deficits Questionnaire-Depression (PDQ-D) at Weeks 6 and 12	The PDQ-D is a 20-item, patient-reported questionnaire with a 7-day recall period. Scores for four subscales. All 20 items use the same 5-point ordinal categorical response scale to reflect the frequency of experiencing a specific cognitive problem in the past 7 days. Scores for each of the four measured subscales are calculated by assigning a value of 0 ("never in the past 7 days"), 1 ("rarely - once or twice"), 2 ("sometimes - 3-5 times"), 3 ("often - about once a day"), or 4 ("very often - more than once a day") to each item, then summing the five items of that subscale, to produce a score ranging from 0 to 20. A total global score for overall cognitive dysfunction (range 0-80) is calculated by summing the four subscale scores. Higher scores for each subscale and for the total score indicate greater perceived cognitive dysfunction. A negative change from Baseline indicates improvement.	Baseline and Weeks 6 and 12
Change From Baseline in Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q) Total Score at Week 12	Q-LES-Q is a scale designed to allow researchers to assess the degree of a participant's quality of life in various areas of daily living. There is not a "Total Score" per se for the Q-LES-Q. The scale is divided into domains. Ninety-one of the 93 items are assembled into 8 categories: physical health/activities, feelings, work, household duties, school/course work, leisure time activities, social relations, and general activities. Items are scored on a 5 point scale, from 1 (not at all or never) to 5 (frequently or all the time), to indicate the degree of enjoyment or satisfaction experienced by domain. Raw summary scores are expressed as a percentage of the maximum possible score within a given domain to facilitate comparisons across areas of functioning. The total score is based on the Overall Life Satisfaction question in General Activities and ranges from 1 to 5. A positive change from baseline indicates greater enjoyment/satisfaction.	Baseline and Week 12
Change From Baseline in 5-Item World Health Organization Well-being Index (WHO-5) Score at Week 12	WHO-5 is a short, self-administered questionnaire covering 5 positively worded items, related to positive mood (good spirits, relaxation), vitality (being active and waking up fresh and rested), and general interests (being interested in things). Each of the five items is rated from 0 (= not present) to 5 (= constantly present). Scores are summated, with raw score ranging from 0 to 25, with higher score meaning better well-being. A positive change from baseline indicates improvement.	Baseline and Week 12
Change From Baseline in Clinical Global Impression Scale Severity (CGI-S) at Week 12	CGI-S is a clinician rated scale designed to assess global severity of illness and change in the clinical condition over time. The CGI-S provides the clinician's impression of the participant's state of mental illness. The clinician uses his or her clinical experience of this participant population to rate the severity of the participant's mental illness on a 7-point scale ranging from 1 (normal-not at all ill) to 7 (among the most extremely ill participants). Higher scores indicate greater severity of illness. A negative change from baseline indicates improvement.	Baseline and Week 12
Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 12	CGI-I assesses the participant's improvement (or worsening). The clinician assessed participant's condition on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicated greater severity of illness.	Week 12

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• McCue M, Sarkey S, Eramo A, Francois C, Parikh SV. Using the Goal Attainment Scale adapted for depression to better understand treatment outcomes in patients with major depressive disorder switching to vortioxetine: a phase 4, single-arm, open-label, multicenter study. BMC Psychiatry. 2021 Dec 11;21(1):622. doi: 10.1186/s12888-021-03608-1. Erratum In: BMC Psychiatry. 2022 Mar 7;22(1):170. BMC Psychiatry. 2022 Jun 8;22(1):388.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2016
• Primary Completion (Actual): February 6, 2018
• Study Completion (Actual): February 6, 2018

Study Registration Dates

• First Submitted: November 21, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (Estimate): November 23, 2016

Study Record Updates

• Last Update Posted (Actual): July 11, 2019
• Last Update Submitted That Met QC Criteria: June 14, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Vortioxetine
• Other Study ID Numbers: Vortioxetine-4003; U1111-1185-6902 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No