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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01179516
Recruitment Status : Completed
First Posted : August 11, 2010
Results First Posted : December 18, 2013
Last Update Posted : December 18, 2013
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE August 9, 2010
First Posted Date  ICMJE August 11, 2010
Results First Submitted Date  ICMJE October 25, 2013
Results First Posted Date  ICMJE December 18, 2013
Last Update Posted Date December 18, 2013
Study Start Date  ICMJE August 2010
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2013)
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Week 8 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2010)
Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score. [ Time Frame: Baseline and Week 8 ]
The change between MADRS total 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.
Change History Complete list of historical versions of study NCT01179516 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2013)
  • Percentage of Participants With a MADRS Response at Week 8 [ Time Frame: Baseline and Week 8 ]
    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.
  • Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8 [ Time Frame: Week 8 ]
    The Clinical Global Impression - global improvement 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 a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline Clinical Global Impression Scale-Severity of Illness (CGI-S) score-by-week as fixed effects.
  • Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥ 20 [ Time Frame: Baseline and Week 8 ]
    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. LS means are from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects. HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56, where lower scores indicate mild severity.
  • Percentage of Participants in MADRS Remission at Week 8 [ Time Frame: Week 8 ]
    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.
  • Change From Baseline in Sheehan Disability Scale (SDS) Total Score [ Time Frame: Baseline and Week 8 ]
    The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family 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 mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline SDS total score-by-week as fixed effects.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2010)
  • 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 ]
    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.
  • Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8 [ Time Frame: Week 8 ]
    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 MADRS total score at Week 8 in subjects with baseline Hamilton Anxiety scale (HAM-A) total score ≥20. [ Time Frame: Baseline and Week 8 ]
    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. HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56.
  • MADRS remission at Week 8, with remission defined as a MADRS total score ≤10. [ Time Frame: Week 8 ]
    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.
  • Change from Baseline in Sheehan Disability Scale (SDS) Total Score. [ Time Frame: Baseline and Week 8 ]
    The change between the SDS total score at week 8 or final visit and the total score collected at baseline. The SDS 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (10 and 15 mg) of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder
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 469 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups—which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

  • Vortioxetine 10 mg
  • Vortioxetine 15 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 14 weeks. Participants made 7 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Depressive Disorder, Major
Intervention  ICMJE
  • Drug: Vortioxetine
    Encapsulated vortioxetine immediate release tablets
    Other Names:
    • Lu AA21004
    • Brintellix®
  • Drug: Placebo
    Vortioxetine placebo-matching capsules
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
    Intervention: Drug: Placebo
  • Experimental: Vortioxetine 10 mg
    Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
    Intervention: Drug: Vortioxetine
  • Experimental: Vortioxetine 15 mg
    Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
    Intervention: Drug: Vortioxetine
Publications * Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder. J Clin Psychiatry. 2015 May;76(5):583-91. doi: 10.4088/JCP.14m09337.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 5, 2012)
469
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2010)
450
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • Has received any investigational compound <30 days before Screening or 5 half-lives prior to Screening.
  • Has received Lu AA21004 in a previous clinical study.
  • Has 1 or more the following:

    1. Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR .
    2. Current 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.
    3. Diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that had not been in sustained full remission for at least 2 years prior to Screening.
    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.
  • The current depressive symptoms of the patient were considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
  • Has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
  • Was currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or planned to initiate such therapy during the study.
  • Has a significant risk of suicide according to the investigator's clinical judgment or had a score ≥5 on item 10 (suicidal thoughts) of the MADRS or had made a suicide attempt in the previous 6 months.
  • Was required to take excluded medications or it was anticipated that would require treatment with at least 1 of the disallowed concomitant medications during the study.
  • Has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, hematological, infectious, dermatological disorder or metabolic disturbance. NOTE: For the purposes of this study, the following conditions were considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.
  • Has 1 or more laboratory value outside the normal range, based on the blood or urine samples taken at the Screening Visit, that were considered by the investigator to be clinically significant; or the patient has any of the following values at the Screening Visit:

    1. A serum creatinine value >1.5 times the upper limits of normal (× ULN).
    2. A total serum total bilirubin value >1.5 × ULN.
    3. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2 × ULN.
  • Has a thyroid stimulating hormone value outside the normal range.
  • Has clinically significant abnormal vital signs.
  • Has an abnormal electrocardiogram.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01179516
Other Study ID Numbers  ICMJE LuAA21004_317
U1111-1116-3223 ( Registry Identifier: WHO )
SU-06032011-7846 ( Registry Identifier: SMCTD )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director, Clinical Science Takeda
PRS Account Takeda
Verification Date October 2013

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