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

December 6, 2010
October 25, 2013
November 2010
March 2012   (final data collection date for primary outcome measure)
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.
Change from Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
The change between MADRS score at week 8 or final visit and MADRS score at baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
Complete list of historical versions of study NCT01255787 on ClinicalTrials.gov Archive Site
  • 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.
  • MADRS response at Week 8, with response defined as a ≥50% decrease in the MADRS total score from Baseline. [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
    The change between MADRS score at week 8 or final visit and MADRS score at baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
  • MADRS remission at Week 8, with remission defined as a MADRS total score ≤10. [ Time Frame: Week 8. ] [ Designated as safety issue: No ]
    MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
  • Clinical Global Impression Scale - Improvement (CGI-I) score at Week 8. [ Time Frame: Week 8. ] [ Designated as safety issue: No ]
    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 from baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater severity of illness.
  • 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 change between the Sheehan Disability Scale total score at week 8 or final visit and the total score collected at baseline. The Sheehan Disability Scale is a 3 item rating scale to assess functional impairment (panic, anxiety, phobic and depressive symptoms) over three inter-related domains (work/school, social life, and family life/home responsibilities) rated on an 11 point scale from 0 (not at all) to 10 (extremely) with a total score range from 0 to 30. Higher scores indicate greater severity of impairment.
Not Provided
Not Provided
 
Efficacy and Safety Study of Vortioxetine (Lu AA21004) for Treatment of Major Depressive Disorder
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

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.

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).

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Depressive Disorder, Major
  • Drug: Vortioxetine
    Vortioxetine tablets
    Other Names:
    • Lu AA21004
    • Brintellix®
  • Drug: Placebo
    Vortioxetine placebo-matching tablets
  • Experimental: Placebo
    Vortioxetine placebo-matching tablets, orally, once daily for up to 10 weeks.
    Intervention: Drug: Placebo
  • 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.
    Interventions:
    • Drug: Vortioxetine
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Vortioxetine
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Vortioxetine
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
600
April 2012
March 2012   (final data collection date for primary outcome measure)

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.
Both
20 Years to 64 Years
No
Contact information is only displayed when the study is recruiting subjects
Croatia,   Finland,   Germany,   Hong Kong,   India,   Japan,   Korea, Republic of,   Latvia,   Malaysia,   Philippines,   Poland,   Romania,   Russian Federation,   Serbia,   Taiwan,   Ukraine
 
NCT01255787
LuAA21004/CCT-002, 2010-022257-41, U1111-1117-6595, JapicCTI-101344, CTRI/2011/08/001963
No
Takeda
Takeda
Not Provided
Study Director: Medical Director Clinical Science Takeda
Takeda
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP