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

NCT ID: NCT01153009

Last Updated: 2013-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 614 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2012-03-31

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.

Detailed Description

The drug that was tested in this study is called Vortioxetine. Vortioxetine is being tested to treat depression in adults who have major depressive disorder (MDD). This study looked at MDD relief in people who took varying dosages of vortioxetine.

The study enrolled 614 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

• Vortioxetine 15 mg
• Vortioxetine 20 mg
• Duloxetine 60 mg
• Placebo (dummy inactive capsule) - this was a capsule that looked like the study drug but had no active ingredient.

All participants were asked to take one capsule at the same time each day throughout the study.

This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 13 weeks. Participants made 9 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.

Conditions

Depressive Disorder, Major

Keywords

Major Depressive Disorder; Depression; Melancholia; Drug Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo-matching capsules

Vortioxetine 15 mg

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.

Group Type: EXPERIMENTAL

Vortioxetine

Intervention Type: DRUG

Encapsulated vortioxetine immediate release tablets

Vortioxetine 20 mg

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.

Group Type: EXPERIMENTAL

Vortioxetine

Intervention Type: DRUG

Encapsulated vortioxetine immediate release tablets

Duloxetine 60 mg

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.

Group Type: ACTIVE_COMPARATOR

Duloxetine

Intervention Type: DRUG

Overencapsulated duloxetine delayed-release capsules

Interventions

Vortioxetine

Encapsulated vortioxetine immediate release tablets

Intervention Type: DRUG

Duloxetine

Overencapsulated duloxetine delayed-release capsules

Intervention Type: DRUG

Placebo

Placebo-matching capsules

Intervention Type: DRUG

Other Intervention Names

Lu AA21004; Brintellix®; Cymbalta®

Eligibility Criteria

Inclusion Criteria

1. 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).

2. The reported duration of the current MDE is at least 3 months.

3. Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.

4. Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.

Exclusion Criteria

1. Has previously participated in a Lu AA21004 clinical study.

2. Has 1 or more the following:

1. Any current psychiatric disorder other than major depressive disorder (MDD) as defined in the DSM-IV-TR (as assessed by the SCID).

2. 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.

3. 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).

4. Presence or history of a clinically significant neurological disorder (including epilepsy).

5. Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).

6. Any Axis II disorder that might compromise the study.

3. 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.

4. Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.

5. Has clinically significant abnormal vital signs as determined by the investigator.

6. Has an abnormal electrocardiogram as determined by the central reader and confirmed as clinically significant by the investigator.

7. Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal.

8. 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.

9. Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.

10. Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.

11. Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. The following are also considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.

12. Has a significant risk of suicide according to the investigator's opinion or has a score greater than or equal to 5 on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale or has made a suicide attempt in the previous 6 months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director, Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Beverly Hills, California, United States

Chino, California, United States

Garden Grove, California, United States

Irvine, California, United States

Los Alamitos, California, United States

Oceanside, California, United States

Pasadena, California, United States

Pico Rivera, California, United States

San Diego, California, United States

Colorado Springs, Colorado, United States

Norwalk, Connecticut, United States

Boca Raton, Florida, United States

Fort Myers, Florida, United States

Gainesville, Florida, United States

Jacksonville, Florida, United States

Lauderhill, Florida, United States

Orlando, Florida, United States

Tampa, Florida, United States

West Palm Beach, Florida, United States

Atlanta, Georgia, United States

Marietta, Georgia, United States

Chicago, Illinois, United States

Libertyville, Illinois, United States

Oakbrook Ter, Illinois, United States

Valparaiso, Indiana, United States

Shreveport, Louisiana, United States

Boston, Massachusetts, United States

Weymouth, Massachusetts, United States

Rochester Hills, Michigan, United States

Flowood, Mississippi, United States

Toms River, New Jersey, United States

Cedarhurst, New York, United States

Fresh Meadows, New York, United States

New York, New York, United States

Rochester, New York, United States

Staten Island, New York, United States

Cincinnati, Ohio, United States

Toledo, Ohio, United States

Oklahoma City, Oklahoma, United States

Portland, Oregon, United States

Allentown, Pennsylvania, United States

Media, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

North Charleston, South Carolina, United States

Memphis, Tennessee, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Irving, Texas, United States

San Antonio, Texas, United States

Orem, Utah, United States

Woodstock, Vermont, United States

Richmond, Virginia, United States

Middleton, Wisconsin, United States

Waukesha, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36708956 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31818787 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25575488 (View on PubMed)

Other Identifiers

U1111-1114-8191

Identifier Type: REGISTRY

Identifier Source: secondary_id

LuAA21004_315

Identifier Type: -

Identifier Source: org_study_id