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Efficacy of Lu AA21004 on Cognitive Dysfunction in Major Depressive Disorder

Primary Purpose

Depressive Disorder, Major

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

vortioxetine (Lu AA21004)

Duloxetine

Placebo

About this trial

This is an interventional treatment trial for Depressive Disorder, Major focused on measuring Drug Therapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
The participant has recurrent MDD as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.3x). The current MDE should be confirmed using the Mini International Neuropsychiatric Interview (MINI) V6.0.0.
The participant has received prescribed treatment for a previous episode of depression.
The participant has a MADRS total score ≥26 at both the screening and baseline visits.
Participant reports subjective cognitive dysfunction (such as difficulty concentrating, slow thinking, and difficulty in learning new things or remembering things).
The reported duration of the current major depressive episode (MDE) is at least 3 months
The participant is a man or woman between 18 and 65 years old, inclusive.
A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study and for 30 days after completion of the study.

Exclusion Criteria:

The participant has previously participated in this study.
The participant has a history of severe drug allergy or hypersensitivity, or known hypersensitivity to any of the excipients of the investigational medicinal product (IMP).
The participant has known hypersensitivity to duloxetine.
The participant has hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase insufficiency.
The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
The participant has a score ≥70 on the DSST (numbers correct) at the Baseline Visit.
The participant is, in the opinion of the investigator, not able to complete the neuropsychological tests validly at the Baseline Visit.
If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.
The participant has 1 or more of the following:
1. Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR (as assessed by the MINI Version 6.0.0).
2. Current or history of attention deficit hyperactivity disorder (ADHD), pervasive developmental disorder, manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
3. Current diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least 2 years prior to Screening. (Participant must also have negative urine drug screen prior to Baseline).
4. Presence or history of a clinically significant neurological disorder (including epilepsy).
5. Neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, etc).
6. Any DSM-IV Axis II disorder that might compromise the study.
The participant has any other disorder for which the treatment takes priority over treatment of MDD or is likely to interfere with study treatment or impair treatment compliance.
The participant has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
The participant is diagnosed with reading disability (dyslexia).
The participant 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.
The participant, in the opinion of the investigator, poses a risk of harm to others.
The participant has initiated formal cognitive or behavioral therapy, systemic psychotherapy within less than 6 months of study screening, or has plans to initiate such therapy during the study.
The participant has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
The current depressive symptoms are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each at the recommended dose.
The participant has a history of moderate or severe head trauma (for example, loss of consciousness for more than 1 hour) or other neurological disorders or systemic medical diseases that are, in the opinion of the investigator, likely to affect central nervous system functioning.
The participant has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of investigational drug. This criterion does not include those participants with basal cell or stage I squamous cell carcinoma of the skin.
The participant has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance.
Note: For the purposes of this protocol, the following conditions are considered unstable due to the potential impact on assessment of MDD response and/or cognitive status: pain disorders, chronic fatigue syndrome, fibromyalgia, obstructive sleep apnea, and known cases of HIV, HBV, and HCV
The participant has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.
The participant 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 evaluation period as specified in the Excluded Medications Section.
The participant has received any investigational compound <30 days before Screening or 5 half-lives prior to Screening.
The participant has clinically significant abnormal vital signs as determined by the investigator.
The subject has thyroid stimulating hormone (TSH) outside the normal range at the Screening Visit.
Note: If TSH value is outside the normal range, a free T4 will be obtained. Subjects who have elevated TSH but normal T4 (i.e. subclinical hypothyroidism) will be excluded. For subjects who are on thyroid hormone replacement therapy, a lower TSH with normal T4, are eligible to participate in the study only if there are no clinical symptoms of hypothyroidism .
The participant 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:
1. A serum creatinine value >1.5 times the upper limits of normal (×ULN).
2. A total serum total bilirubin value >1.5×ULN.
3. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2×ULN.
The participant has an abnormal electrocardiogram (ECG) as determined by the central reader and confirmed as clinically significant by the investigator.
The participant 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.
The participant has been previously exposed to LuAA21004 compound.
The participant has a history of lack of response to previous adequate treatment with duloxetine.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Vortioxetine (Lu AA21004) QD

Duloxetine QD

Placebo QD

Arm Description

Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.

Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.

Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).

Outcomes

Primary Outcome Measures

Change From Baseline to Week 8 in the Digit Symbol Substitution Test (DSST)

The DSST assesses relative contributions of speed, memory, executive function and visual scanning. Participants are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time for a total possible score of 0 to 133. Higher scores-correct number of symbols reflects greater objective cognitive functioning. An increase in score represents an improvement in an integrated measure of cognitive function. An Analysis of Covariance (ANCOVA) model was used with treatment and center as fixed factors and the Baseline value as a covariate.

Secondary Outcome Measures

Change From Baseline to Week 8 in the Perceived Deficits Questionnaire (PDQ) Attention/Concentration and Planning/Organization Subscore

PDQ is a patient-rated scale designed to subjectively assess cognitive dysfunction, comprising four 5-item subscales: Attention/Concentration, Retrospective Memory, Prospective Memory, and Planning/Organization for a total possible score of 0 to 40. The subscale Attention/Concentration is the sum of items 1, 5, 9, 13, and 17 with a range of 0-20; while the subscale Planning/Organization is the sum of items 4, 8, 12, 16, and 20 with the score range of 0 to 20. The scores of the subscales Attention/Concentration and Planning/Organization were summed. Higher scores reflect greater participant-perceived cognitive dysfunction in the domains identified. A decrease in score represents an improvement in subjective cognitive function in the domains identified. A Mixed Model Repeated Measures (MMRM) model was used with baseline*week, center, week, treatment and week*treatment as factors in the analysis.

Clinical Global Impressions-Improvement (CGI-I) Score at Week 8

The CGI-I assesses the clinician's impression of the subject's state of mental illness improvement and consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on a seven-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change relative to baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater worsening of illness. Values closest to 1 for this outcome measure indicate the greatest improvement of symptoms. A MMRM model was used with baseline*week, center, week, treatment and week*treatment as factors in the analysis.

Change From Baseline to Week 8 in the Trail Making Test (TMT-A)

The TMT is a two-part cognitive test. TMT-A assesses cognitive processing speed and consists of 25 circles distributed over a sheet of paper. Participants have 4 minutes to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Tester informs participant immediately whenever they make an error and allows for corrections by participants. Lower scores represent better speed of processing. A decrease in score over the study represents an improvement in speed in processing. An ANCOVA model was used with treatment and center as fixed factors and the baseline value as a covariate.

Change From Baseline to Week 8 in the Trail Making Test B (TMT-B)

The TMT is a two-part cognitive test. TMT-B assesses executive functioning and consists of 25 circles distributed over a sheet of paper. Participants have 4 minutes to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Tester informs participant immediately whenever they make an error and allows for corrections by participants. Lower score for TMT-B represents better executive function. A decrease in score over the study represents an improvement in executive function. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.

Change in Time From Baseline to Week 8 in the Stroop Test

The STROOP test assesses the ability to inhibit a prepotent response to reading words while performing a task that requires attention control. It comprises of 2 sheets with 50 words each, up to 50 correct responses for each of the congruent and incongruent Stroop tests. Participants have 4 minutes to name the ink color of each word. Lower time to complete the test indicates better performance. Higher number of correct responses indicates better responses. A decrease in the time to complete the tests and an increase in the number of correct responses both indicate improvement over the course of the study. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.

Change From Baseline to Week 8 in the Groton Maze Learning Test (GMLT)

The GMLT measures executive functioning and spatial problem solving. Participants learn a hidden pathway through a maze of 10 x 10 grid of tiles on a computer touch screen using step-by-step guess, with trial and error feedback after each step. Once the pathway is learned, participants repeat the same pathway four more times. It usually takes 5-6 minutes to administer this test. Lower score equals better performance. A decrease in score over the course of the study indicates improved executive function. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.

Change From Baseline to Week 8 in the Detection Task (DT)

The DT is a computerized test that measures simple reaction time and psychomotor speed. The task requires participants to respond by pressing a "yes" button as soon as an onscreen playing card is turned over and is red, and by pressing a "no" button if the card is not red. It takes 2 minutes to be administered. There is no minimum or maximum scores since it is a time-based assessment. Lower score equals better performance. A decrease in score over the course of the study indicates improved speed of processing and psychomotor function. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.

Change From Baseline to Week 8 in the Identification Task (IT)

The IT measured choice reaction time: the participant pressed a "yes" button whenever an onscreen playing card turned face up and was red, or a "no" button if the card was not red. The IT took on average 2 minutes to complete. Lower scores equal better performance. A decrease in score over the course of the study indicates improved visual attention/vigilance. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.

Change From Baseline to Week 8 in the One-Back Task

The One-Back test measures the cognitive domain of attention and working memory through yes or no responses to 30 trials. The task requires participants to report when a stimulus item presented serially is the same as an item one step back from the item at hand for a total correct responses 0 to 100. It usually takes 2-3 minutes to be administered. Higher scores equal better performance. An increase in score over the course of the study indicates improved attention/working memory. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.

Proportion of Cognitive Dysfunction Improvement Due to Improvement of Depression

Improvement of Cognitive Dysfunction is determined using the change from Baseline to Week 8 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score and the Digital Symbol Substitution Test (DSST) total number of correct symbols. The MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression). The DSST assesses relative contributions of speed, memory, executive function and visual scanning. The proportion of direct effect from treatment = DSST difference / (DSST difference + coefficient*MADRS difference).

Change From Baseline to Week 8 in the MADRS Total Score

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.

Percentage of Participants With MADRS Response at Week 8

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. MADRS Response was defined as a ≥50% decrease in MADRS Total Score from Baseline.

Percentage of Participants in MADRS Remission at Week 8

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. MADRS Remission was defined as a MADRS total score ≤10.

Change From Baseline to Week 8 in the Clinical Global Impressions-Severity (CGI-S) Score

The CGI-S assesses the clinician's impression of the subject's current state of mental illness and consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill). A MMRM model with baseline*week, center, week, treatment and week*treatment as factors was used for analyses.

Full Information

NCT ID

NCT01564862

First Posted

March 26, 2012

Last Updated

February 4, 2015

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT01564862

Brief Title

Efficacy of Lu AA21004 on Cognitive Dysfunction in Major Depressive Disorder

Official Title

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Active-Referenced, Flexible Dose Study on the Efficacy of Lu AA21004 on Cognitive Dysfunction in Adult Subjects With Major Depressive Disorder (MDD)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2015

Overall Recruitment Status

Completed

Study Start Date

April 2012 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the effects of Lu AA21004, once daily (QD), on cognitive dysfunction in patients with major depressive disorder.

Detailed Description

Lu AA21004 is under codevelopment by Takeda Global Research & Development Center, Inc. and H. Lundbeck A/S for the treatment of MDD. This study will consist of a screening period within 10 days of the Baseline Visit followed by an 8-week double-blind treatment period and a one-week taper down period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Depressive Disorder, Major

Keywords

Drug Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

602 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vortioxetine (Lu AA21004) QD

Arm Type

Experimental

Arm Description

Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.

Arm Title

Duloxetine QD

Arm Type

Active Comparator

Arm Description

Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.

Arm Title

Placebo QD

Arm Type

Placebo Comparator

Arm Description

Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).

Intervention Type

Drug

Intervention Name(s)

vortioxetine (Lu AA21004)

Intervention Description

Lu AA21004 capsules

Intervention Type

Drug

Intervention Name(s)

Duloxetine

Other Intervention Name(s)

Cymbalta

Intervention Description

Duloxetine capsules

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo matching capsules

Primary Outcome Measure Information:

Title

Change From Baseline to Week 8 in the Digit Symbol Substitution Test (DSST)

Description

Time Frame

Baseline and Week 8

Secondary Outcome Measure Information:

Title

Change From Baseline to Week 8 in the Perceived Deficits Questionnaire (PDQ) Attention/Concentration and Planning/Organization Subscore

Description

Time Frame

Baseline and Week 8

Title

Clinical Global Impressions-Improvement (CGI-I) Score at Week 8

Description

Time Frame

Baseline, Week 8

Title

Change From Baseline to Week 8 in the Trail Making Test (TMT-A)

Description

Time Frame

Baseline and Week 8

Title

Change From Baseline to Week 8 in the Trail Making Test B (TMT-B)

Description

Time Frame

Baseline and Week 8

Title

Change in Time From Baseline to Week 8 in the Stroop Test

Description

Time Frame

Baseline and Week 8

Title

Change From Baseline to Week 8 in the Groton Maze Learning Test (GMLT)

Description

Time Frame

Baseline and Week 8

Title

Change From Baseline to Week 8 in the Detection Task (DT)

Description

Time Frame

Baseline and Week 8

Title

Change From Baseline to Week 8 in the Identification Task (IT)

Description

Time Frame

Baseline and Week 8

Title

Change From Baseline to Week 8 in the One-Back Task

Description

Time Frame

Baseline and Week 8

Title

Proportion of Cognitive Dysfunction Improvement Due to Improvement of Depression

Description

Time Frame

Baseline and Week 8

Title

Change From Baseline to Week 8 in the MADRS Total Score

Description

Time Frame

Baseline, Week 1, Week 4 and Week 8

Title

Percentage of Participants With MADRS Response at Week 8

Description

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. MADRS Response was defined as a ≥50% decrease in MADRS Total Score from Baseline.

Time Frame

Baseline and Week 8

Title

Percentage of Participants in MADRS Remission at Week 8

Description

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. MADRS Remission was defined as a MADRS total score ≤10.

Time Frame

Week 8

Title

Change From Baseline to Week 8 in the Clinical Global Impressions-Severity (CGI-S) Score

Description

Time Frame

Baseline, Week 1, Week 4 and Week 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. The participant has recurrent MDD as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.3x). The current MDE should be confirmed using the Mini International Neuropsychiatric Interview (MINI) V6.0.0. The participant has received prescribed treatment for a previous episode of depression. The participant has a MADRS total score ≥26 at both the screening and baseline visits. Participant reports subjective cognitive dysfunction (such as difficulty concentrating, slow thinking, and difficulty in learning new things or remembering things). The reported duration of the current major depressive episode (MDE) is at least 3 months The participant is a man or woman between 18 and 65 years old, inclusive. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study and for 30 days after completion of the study. Exclusion Criteria: The participant has previously participated in this study. The participant has a history of severe drug allergy or hypersensitivity, or known hypersensitivity to any of the excipients of the investigational medicinal product (IMP). The participant has known hypersensitivity to duloxetine. The participant has hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase insufficiency. The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress. The participant has a score ≥70 on the DSST (numbers correct) at the Baseline Visit. The participant is, in the opinion of the investigator, not able to complete the neuropsychological tests validly at the Baseline Visit. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period. The participant has 1 or more of the following: Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR (as assessed by the MINI Version 6.0.0). Current or history of attention deficit hyperactivity disorder (ADHD), pervasive developmental disorder, manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR. Current diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least 2 years prior to Screening. (Participant must also have negative urine drug screen prior to Baseline). Presence or history of a clinically significant neurological disorder (including epilepsy). Neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, etc). Any DSM-IV Axis II disorder that might compromise the study. The participant has any other disorder for which the treatment takes priority over treatment of MDD or is likely to interfere with study treatment or impair treatment compliance. The participant has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests. The participant is diagnosed with reading disability (dyslexia). The participant 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. The participant, in the opinion of the investigator, poses a risk of harm to others. The participant has initiated formal cognitive or behavioral therapy, systemic psychotherapy within less than 6 months of study screening, or has plans to initiate such therapy during the study. The participant has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening. The current depressive symptoms are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each at the recommended dose. The participant has a history of moderate or severe head trauma (for example, loss of consciousness for more than 1 hour) or other neurological disorders or systemic medical diseases that are, in the opinion of the investigator, likely to affect central nervous system functioning. The participant has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of investigational drug. This criterion does not include those participants with basal cell or stage I squamous cell carcinoma of the skin. The participant has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. Note: For the purposes of this protocol, the following conditions are considered unstable due to the potential impact on assessment of MDD response and/or cognitive status: pain disorders, chronic fatigue syndrome, fibromyalgia, obstructive sleep apnea, and known cases of HIV, HBV, and HCV The participant has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma. The participant 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 evaluation period as specified in the Excluded Medications Section. The participant has received any investigational compound <30 days before Screening or 5 half-lives prior to Screening. The participant has clinically significant abnormal vital signs as determined by the investigator. The subject has thyroid stimulating hormone (TSH) outside the normal range at the Screening Visit. Note: If TSH value is outside the normal range, a free T4 will be obtained. Subjects who have elevated TSH but normal T4 (i.e. subclinical hypothyroidism) will be excluded. For subjects who are on thyroid hormone replacement therapy, a lower TSH with normal T4, are eligible to participate in the study only if there are no clinical symptoms of hypothyroidism . The participant 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: A serum creatinine value >1.5 times the upper limits of normal (×ULN). A total serum total bilirubin value >1.5×ULN. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2×ULN. The participant has an abnormal electrocardiogram (ECG) as determined by the central reader and confirmed as clinically significant by the investigator. The participant 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. The participant has been previously exposed to LuAA21004 compound. The participant has a history of lack of response to previous adequate treatment with duloxetine.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Senior Medical Director Clinical Science

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

City

Tucson

State/Province

Arizona

Country

United States

City

Little Rock

State/Province

Arkansas

Country

United States

City

Bellflower

State/Province

California

Country

United States

City

Carson

State/Province

California

Country

United States

City

Cerritos

State/Province

California

Country

United States

City

Glendale

State/Province

California

Country

United States

City

Imperial

State/Province

California

Country

United States

City

Los Angeles

State/Province

California

Country

United States

City

Norwalk

State/Province

California

Country

United States

City

Oakland

State/Province

California

Country

United States

City

Paramount

State/Province

California

Country

United States

City

San Bernardino

State/Province

California

Country

United States

City

Santa Ana

State/Province

California

Country

United States

City

Wildomar

State/Province

California

Country

United States

City

Colorado Springs

State/Province

Colorado

Country

United States

City

Denver

State/Province

Colorado

Country

United States

City

Norwalk

State/Province

Connecticut

Country

United States

City

Lauderhill

State/Province

Florida

Country

United States

City

Miami

State/Province

Florida

Country

United States

City

Orlando

State/Province

Florida

Country

United States

City

Sanford

State/Province

Florida

Country

United States

City

St. Petersburg

State/Province

Florida

Country

United States

City

Tampa

State/Province

Florida

Country

United States

City

West Palm Beach

State/Province

Florida

Country

United States

City

Chicago

State/Province

Illinois

Country

United States

City

Hoffman Estates

State/Province

Illinois

Country

United States

City

Naperville

State/Province

Illinois

Country

United States

City

Oak Brook

State/Province

Illinois

Country

United States

City

Skokie

State/Province

Illinois

Country

United States

City

Indianapolis

State/Province

Indiana

Country

United States

City

Prairie Village

State/Province

Kansas

Country

United States

City

Shreveport

State/Province

Louisiana

Country

United States

City

Baltimore

State/Province

Maryland

Country

United States

City

Haverhill

State/Province

Massachusetts

Country

United States

City

St. Louis

State/Province

Missouri

Country

United States

City

North Platte

State/Province

Nebraska

Country

United States

City

Las Vegas

State/Province

Nevada

Country

United States

City

Buffalo

State/Province

New York

Country

United States

City

New York

State/Province

New York

Country

United States

City

Staten Island

State/Province

New York

Country

United States

City

Avon lake

State/Province

Ohio

Country

United States

City

Beachwood

State/Province

Ohio

Country

United States

City

Garfield Heights

State/Province

Ohio

Country

United States

City

Toledo

State/Province

Ohio

Country

United States

City

Oklahoma City

State/Province

Oklahoma

Country

United States

City

Portland

State/Province

Oregon

Country

United States

City

Allentown

State/Province

Pennsylvania

Country

United States

City

Norristown

State/Province

Pennsylvania

Country

United States

City

Philadelphia

State/Province

Pennsylvania

Country

United States

City

Columbia

State/Province

South Carolina

Country

United States

City

Franklin

State/Province

Tennessee

Country

United States

City

Memphis

State/Province

Tennessee

Country

United States

City

Dallas

State/Province

Texas

Country

United States

City

Houston

State/Province

Texas

Country

United States

City

San Antonio

State/Province

Texas

Country

United States

City

The Woodlands

State/Province

Texas

Country

United States

City

Orem

State/Province

Utah

Country

United States

City

Salt Lake City

State/Province

Utah

Country

United States

City

Kirkland

State/Province

Washington

Country

United States

City

Seattle

State/Province

Washington

Country

United States

City

Brown Deer

State/Province

Wisconsin

Country

United States

City

Milwaukee

State/Province

Wisconsin

Country

United States

City

Kazanlak

Country

Bulgaria

City

Novi Iskar

Country

Bulgaria

City

Pleven

Country

Bulgaria

City

Plovdiv

Country

Bulgaria

City

Sofia

Country

Bulgaria

City

Tzerova Koria

Country

Bulgaria

City

Helsinki

Country

Finland

City

Kuopio

Country

Finland

City

Turku

Country

Finland

City

Berlin

Country

Germany

City

Bochum

Country

Germany

City

Chemnitz

Country

Germany

City

Hannover

Country

Germany

City

Munchen

Country

Germany

City

Schwerin

Country

Germany

City

Westerstede

Country

Germany

City

Wiesbaden

Country

Germany

City

Bialystok

Country

Poland

City

Leszno

Country

Poland

City

Lodz

Country

Poland

City

Torun

Country

Poland

City

Ekaterinburg

Country

Russian Federation

City

Nizhny Novgorod

Country

Russian Federation

City

Saint-Petersburg

Country

Russian Federation

City

Smolensk

Country

Russian Federation

City

Stavropol

Country

Russian Federation

City

Kharkiv

Country

Ukraine

City

Kyiv

Country

Ukraine

City

Luhansk

Country

Ukraine

City

Ternopil

Country

Ukraine

12. IPD Sharing Statement

Citations:

PubMed Identifier

31422713

Citation

Jacobson W, Zhong W, Nomikos GG, Christensen MC, Kurre Olsen C, Harvey PD. Effects of vortioxetine on functional capacity across different levels of functional impairment in patients with major depressive disorder: a University of California, San Diego Performance-based Skills Assessment (UPSA) analysis. Curr Med Res Opin. 2020 Jan;36(1):117-124. doi: 10.1080/03007995.2019.1657692. Epub 2019 Aug 29.

Results Reference

derived

PubMed Identifier

30439678

Citation

Christensen MC, Sluth LB, McIntyre RS. Validation of the University of California San Diego Performance-based Skills Assessment (UPSA) in major depressive disorder: Replication and extension of initial findings. J Affect Disord. 2019 Feb 15;245:508-516. doi: 10.1016/j.jad.2018.11.034. Epub 2018 Nov 5.

Results Reference

derived

PubMed Identifier

29689693

Citation

Christensen MC, Loft H, McIntyre RS. Vortioxetine improves symptomatic and functional outcomes in major depressive disorder: A novel dual outcome measure in depressive disorders. J Affect Disord. 2018 Feb;227:787-794. doi: 10.1016/j.jad.2017.11.081. Epub 2017 Nov 16.

Results Reference

derived

PubMed Identifier

29546401

Citation

Keefe RSE, Nomikos G, Zhong W, Christensen MC, Jacobson W. A Subgroup Analysis of the Impact of Vortioxetine on Functional Capacity, as Measured by UPSA, in Patients with Major Depressive Disorder and Subjective Cognitive Dysfunction. Int J Neuropsychopharmacol. 2018 May 1;21(5):442-447. doi: 10.1093/ijnp/pyy020.

Results Reference

derived

PubMed Identifier

29235884

Citation

Christensen MC, Munro V. Cost per successfully treated patient for vortioxetine versus duloxetine in adults with major depressive disorder: an analysis of the complete symptoms of depression and functional outcome. Curr Med Res Opin. 2018 Apr;34(4):593-600. doi: 10.1080/03007995.2017.1416952. Epub 2018 Jan 16.

Results Reference

derived

PubMed Identifier

28213121

Citation

Harvey PD, Jacobson W, Zhong W, Nomikos GG, Cronquist Christensen M, Kurre Olsen C, Merikle E. Determination of a clinically important difference and definition of a responder threshold for the UCSD performance-based skills assessment (UPSA) in patients with major depressive disorder. J Affect Disord. 2017 Apr 15;213:105-111. doi: 10.1016/j.jad.2017.02.014. Epub 2017 Feb 14.

Results Reference

derived

Learn more about this trial

Efficacy of Lu AA21004 on Cognitive Dysfunction in Major Depressive Disorder

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