Efficacy and Safety Study of Vortioxetine (Lu AA21004) for Treatment of Major Depressive Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01255787
First received: December 6, 2010
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to assess the efficacy and safety of multiple doses of vortioxetine, once daily (QD), in participants with major depressive disorder.


Condition Intervention Phase
Depressive Disorder, Major
Drug: Vortioxetine
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multinational, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Assess the Efficacy and Safety of Lu AA21004 in Patients With Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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 were from an Analysis of Covariance (ANCOVA) model with treatment as a fixed factor and the Baseline value as a covariate.


Secondary Outcome Measures:
  • Percentage of Participants With a MADRS Response at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Response is defined as a participant with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.

  • Percentage of Participants in MADRS Remission at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.

  • Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    The Clinical Global Impression - Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from an ANCOVA model with treatment as a fixed factor and the Baseline Clinical Global Impression-Severity of Illness (CGI-S) score as a covariate.

  • Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and family life or home responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means were from an ANCOVA model with treatment as a fixed factor and the Baseline value as a covariate.


Enrollment: 600
Study Start Date: November 2010
Study Completion Date: April 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo
Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.
Drug: Placebo
Vortioxetine placebo-matching tablets
Experimental: Vortioxetine 5 mg
Vortioxetine 5 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.
Drug: Vortioxetine
Vortioxetine tablets
Other Names:
  • Lu AA21004
  • Brintellix®
Drug: Placebo
Vortioxetine placebo-matching tablets
Experimental: Vortioxetine 10 mg
Vortioxetine 10 mg, tablets, orally, once daily for 8 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily for 2 weeks.
Drug: Vortioxetine
Vortioxetine tablets
Other Names:
  • Lu AA21004
  • Brintellix®
Drug: Placebo
Vortioxetine placebo-matching tablets
Experimental: Vortioxetine 20 mg
Vortioxetine 10 mg, tablets, orally, once daily for 1 week, followed by vortioxetine 20 mg, tablets, orally, once daily for 7 weeks, followed by vortioxetine placebo-matching tablets, orally, once daily, for 2 weeks.
Drug: Vortioxetine
Vortioxetine tablets
Other Names:
  • Lu AA21004
  • Brintellix®
Drug: Placebo
Vortioxetine placebo-matching tablets

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 doses of vortioxetine.

The study enrolled 600 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 5 mg
  • Vortioxetine 10 mg
  • Vortioxetine 20 mg
  • Placebo (dummy inactive pill) - 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 14 countries in Europe and Asia. The overall time to participate in this study was up to 13 weeks. Participants made weekly visits to the clinic during the first 2 weeks of the 8-week treatment period and then every 2 weeks up to the end of the 8-week treatment period. Participants who completed the 8-week treatment period entered a 2-week discontinuation period to assess potential discontinuation symptoms 1 and 2 weeks after the end of the 8-week treatment period. A safety follow-up contact (visit or phone call) was made 4 weeks after completion of the 8-week double-blind treatment period (2 weeks after the end of the 2-week discontinuation period).

  Eligibility

Ages Eligible for Study:   20 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Suffers from Major Depressive Disorder as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.2x and 296.3x).
  2. The reported duration of the current major depressive episode is at least 3 months at the Screening Visit.
  3. Has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26 at the Screening and Baseline Visits.
  4. Has a Clinical Global Impression Scale-Severity (CGI-S) score ≥4 at the Screening and Baseline Visits.

Exclusion Criteria:

  1. Has one or more of the following conditions:

    • Any current psychiatric disorder other than Major Depressive Disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR; assessed by the Mini International Neuropsychiatric Interview: MINI). A participant who exhibits symptoms of anxiety is eligible unless fulfilling the diagnostic criteria for a current anxiety disorder per DSM-IV-TR.
    • Current diagnosis or 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.
    • Current diagnosis or history of any substance-related disorder (except nicotine and caffeine-related disorders) as defined in the DSM-IV-TR. Participant with confirmed positive urine drug screens (except prescribed medications or a medication that does not constitute drug abuse) will be excluded.
    • 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-TR axis II disorder that might compromise the study.
  2. The current depressive symptoms of the participant are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
  3. Has received electroconvulsive, vagal nerve stimulation, or repetitive transcranial magnetic stimulation therapy within 6 months prior to the Screening Visit.
  4. Is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
  5. Is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide within 6 months prior to the Screening Visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01255787

  Show 73 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Clinical Science Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01255787     History of Changes
Other Study ID Numbers: LuAA21004/CCT-002, 2010-022257-41, U1111-1117-6595, JapicCTI-101344, CTRI/2011/08/001963
Study First Received: December 6, 2010
Results First Received: October 25, 2013
Last Updated: October 25, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
Croatia: Agency for Medicinal Product and Medical Devices
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Russia: Department of State Regulation of Circulation of Medical Remedies
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Ukraine: State Pharmacological Center - Ministry of Health
Hong Kong: Department of Health
India: Drugs Controller General of India
South Korea: Korea Food and Drug Administration (KFDA)
Malaysia: National Pharmaceutical Control Bureau
Philippines : Food and Drug Administration
Taiwan: Taiwan Food and Drug Administration

Keywords provided by Takeda:
Major Depressive Disorder
Depression
Melancholia
Drug Therapy

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Vortioxetine
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin 5-HT1 Receptor Antagonists
Serotonin Antagonists
Serotonin 5-HT3 Receptor Antagonists

ClinicalTrials.gov processed this record on August 20, 2014