Safety and Efficacy of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

NCT01153009 | Completed Phase 3 Results

• 2 other identifiers: LuAA21004_315U1111-1114-8191
• Study Type: interventional
• Target: 614
• Locations: 1 country
• Sites: 56

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and tolerability of vortioxetine, once daily (QD), compared with placebo in adults with major depressive disorder.

Conditions

Depressive Disorder, Major

Keywords

Major Depressive Disorder; Depression; Melancholia; Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

  The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.

  Baseline and Week 8

Secondary Outcomes (5)

• Percentage of Participants With a MADRS Response at Week 8

  Baseline and Week 8

• Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8

  Week 8

• Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥20

  Baseline and Week 8

• Percentage of Participants in MADRS Remission at Week 8

  Week 8

• Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8

  Baseline and Week 8

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo-matching capsules, orally, once daily for up to 9 weeks.

Drug: Placebo

Vortioxetine 15 mg

EXPERIMENTAL

Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.

Drug: Vortioxetine

Vortioxetine 20 mg

EXPERIMENTAL

Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.

Drug: Vortioxetine

Duloxetine 60 mg

ACTIVE COMPARATOR

Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.

Drug: Duloxetine

Interventions

Vortioxetine DRUG

Encapsulated vortioxetine immediate release tablets

Also known as: Lu AA21004, Brintellix®

Vortioxetine 15 mg; Vortioxetine 20 mg

Duloxetine DRUG

Overencapsulated duloxetine delayed-release capsules

Also known as: Cymbalta®

Duloxetine 60 mg

Placebo DRUG

Placebo-matching capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or a woman who suffers from a major depressive episode (MDE) recurrent as the primary diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.3x) as confirmed by the Structured Clinical Interview for DSM Disorders (SCID).
• The reported duration of the current MDE is at least 3 months.
• Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.
• Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.

You may not qualify if:

• Has previously participated in a Lu AA21004 clinical study.
• Has 1 or more the following:
• Any current psychiatric disorder other than major depressive disorder (MDD) as defined in the DSM-IV-TR (as assessed by the SCID).
• Current or past history of: 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.
• Diagnosis of any substance abuse or dependence (except nicotine and caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least 2 years prior to screening (subject must also have negative urine drug screen prior to Baseline).
• Presence or history of a clinically significant neurological disorder (including epilepsy).
• Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
• Any Axis II disorder that might compromise the study.
• 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. Has 1 or more laboratory values 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.
• Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.
• Has clinically significant abnormal vital signs as determined by the investigator.
• Has an abnormal electrocardiogram as determined by the central reader and confirmed as clinically significant by the investigator.
• Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal.
• Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those patients with basal cell or Stage I squamous cell carcinoma of the skin.
• Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.

Sponsors & Collaborators

• Takeda: lead

Study Sites (56)

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Beverly Hills, California, United States

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Chino, California, United States

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Garden Grove, California, United States

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Irvine, California, United States

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Los Alamitos, California, United States

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Oceanside, California, United States

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Pasadena, California, United States

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Pico Rivera, California, United States

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San Diego, California, United States

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Colorado Springs, Colorado, United States

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Norwalk, Connecticut, United States

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Boca Raton, Florida, United States

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Fort Myers, Florida, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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Lauderhill, Florida, United States

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Orlando, 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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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Chicago, Illinois, United States

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Libertyville, Illinois, United States

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Oakbrook Ter, Illinois, United States

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Valparaiso, Indiana, United States

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Shreveport, Louisiana, United States

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Boston, Massachusetts, United States

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Weymouth, Massachusetts, United States

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Rochester Hills, Michigan, United States

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Flowood, Mississippi, United States

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Toms River, New Jersey, United States

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Cedarhurst, New York, United States

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Fresh Meadows, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Staten Island, New York, United States

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Cincinnati, 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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Media, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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North Charleston, South Carolina, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Irving, Texas, United States

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San Antonio, Texas, United States

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Orem, Utah, United States

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Woodstock, Vermont, United States

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Richmond, Virginia, United States

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Middleton, Wisconsin, United States

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Waukesha, Wisconsin, United States

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Related Publications (3)

• Adair M, Christensen MC, Florea I, Loft H, Fagiolini A. Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerability. J Affect Disord. 2023 May 1;328:345-354. doi: 10.1016/j.jad.2023.01.074. Epub 2023 Jan 26.

  PMID: 36708956 DERIVED

• Christensen MC, Florea I, Loft H, McIntyre RS. Efficacy of vortioxetine in patients with major depressive disorder reporting childhood or recent trauma. J Affect Disord. 2020 Feb 15;263:258-266. doi: 10.1016/j.jad.2019.11.074. Epub 2019 Nov 13.

  PMID: 31818787 DERIVED

• Mahableshwarkar AR, Jacobsen PL, Chen Y, Serenko M, Trivedi MH. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015 Jun;232(12):2061-70. doi: 10.1007/s00213-014-3839-0. Epub 2015 Jan 11.

  PMID: 25575488 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Depressive Disorder

Interventions

Vortioxetine; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• 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 3
• 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: June 28, 2010
• First Posted: June 29, 2010
• Study Start: June 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: December 18, 2013
• Results First Posted: December 18, 2013

Record last verified: 2013-10

Locations

US (56)