Efficacy of Lu AA21004 on Cognitive Dysfunction in Major Depressive Disorder

NCT01564862 | Completed Phase 2 Results

• 3 other identifiers: LuAA21004_2022011-005298-22U1111-1126-0091
• Study Type: interventional
• Target: 602
• Locations: 7 countries
• Sites: 92

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.

Conditions

Depressive Disorder, Major

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and Week 8

Secondary Outcomes (14)

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

  Baseline and Week 8

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

  Baseline, Week 8

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

  Baseline and Week 8

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

  Baseline and Week 8

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

  Baseline and Week 8

Study Arms (3)

Vortioxetine (Lu AA21004) QD

EXPERIMENTAL

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.

Drug: vortioxetine (Lu AA21004)

Duloxetine QD

ACTIVE COMPARATOR

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

Drug: Duloxetine

Placebo QD

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

vortioxetine (Lu AA21004) DRUG

Lu AA21004 capsules

Vortioxetine (Lu AA21004) QD

Duloxetine DRUG

Duloxetine capsules

Also known as: Cymbalta

Duloxetine QD

Placebo DRUG

Placebo matching capsules

Placebo QD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (92)

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Bellflower, California, United States

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Carson, California, United States

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Cerritos, California, United States

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Glendale, California, United States

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Imperial, California, United States

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Los Angeles, California, United States

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Norwalk, California, United States

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Oakland, California, United States

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Paramount, California, United States

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San Bernardino, California, United States

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Santa Ana, California, United States

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Wildomar, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Norwalk, Connecticut, United States

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Lauderhill, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Sanford, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Chicago, Illinois, United States

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Hoffman Estates, Illinois, United States

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Naperville, Illinois, United States

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Oak Brook, Illinois, United States

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Skokie, Illinois, United States

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Indianapolis, Indiana, United States

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Prairie Village, Kansas, United States

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Shreveport, Louisiana, United States

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Baltimore, Maryland, United States

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Haverhill, Massachusetts, United States

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St Louis, Missouri, United States

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North Platte, Nebraska, United States

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Las Vegas, Nevada, United States

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Buffalo, New York, United States

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New York, New York, United States

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Staten Island, New York, United States

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Avon Lake, Ohio, United States

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Beachwood, Ohio, United States

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Garfield Heights, Ohio, United States

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Toledo, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Allentown, Pennsylvania, United States

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Norristown, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Columbia, South Carolina, United States

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Franklin, Tennessee, United States

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Memphis, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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The Woodlands, Texas, United States

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Orem, Utah, United States

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Salt Lake City, Utah, United States

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Kirkland, Washington, United States

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Seattle, Washington, United States

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Brown Deer, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Kazanlak, Bulgaria

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Novi Iskar, Bulgaria

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Sofia, Bulgaria

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Tzerova Koria, Bulgaria

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Helsinki, Finland

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Kuopio, Finland

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Turku, Finland

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Berlin, Germany

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Bochum, Germany

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Chemnitz, Germany

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Hanover, Germany

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München, Germany

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Schwerin, Germany

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Westerstede, Germany

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Wiesbaden, Germany

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Bialystok, Poland

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Leszno, Poland

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Lodz, Poland

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Torun, Poland

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Nizhny Novgorod, Russia

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Saint Petersburg, Russia

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Smolensk, Russia

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Stavropol, Russia

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Yekaterinburg, Russia

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Kharkiv, Ukraine

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Kyiv, Ukraine

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Luhansk, Ukraine

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Ternopil, Ukraine

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Related Publications (6)

• 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.

  PMID: 31422713 DERIVED

• 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.

  PMID: 30439678 DERIVED

• 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.

  PMID: 29689693 DERIVED

• 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.

  PMID: 29546401 DERIVED

• 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.

  PMID: 29235884 DERIVED

• 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.

  PMID: 28213121 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Vortioxetine; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiophenes; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

clinicaltrialregistry@tpna.com

+1-877-825-3327

Study Officials

• Senior Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2012
• First Posted: March 28, 2012
• Study Start: April 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: February 5, 2015
• Results First Posted: February 5, 2015

Record last verified: 2015-02

Locations

PL (4); FI (3); US (62); BU (6); DE (8); RU (5); UA (4)