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Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)

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ClinicalTrials.gov Identifier: NCT02371980
Recruitment Status : Completed
First Posted : February 26, 2015
Results First Posted : April 17, 2020
Last Update Posted : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE February 20, 2015
First Posted Date  ICMJE February 26, 2015
Results First Submitted Date  ICMJE April 3, 2020
Results First Posted Date  ICMJE April 17, 2020
Last Update Posted Date April 17, 2020
Actual Study Start Date  ICMJE February 10, 2015
Actual Primary Completion Date March 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2020)
Time From Randomization to Relapse of Major Depressive Disorder During the First 28 Weeks of the 32-Week Double-Blind Treatment Period [ Time Frame: From date of double-blind randomization (Week 16) up to relapse or first 28 weeks of Double-blind Period which occurs first (Up to Week 44) ]
Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored at date of withdrawal or date of Week 28 visit, whichever was earliest. 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 ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The inter-quartile range (IQR) was 25th percentile to 75th percentile.
Original Primary Outcome Measures  ICMJE
 (submitted: February 20, 2015)
Time From Randomization to Relapse of Major Depressive Disorder During the First 28 Weeks of the 32-Week Double-Blind Treatment Period [ Time Frame: From date of double-blind randomization (Week 16) to relapse (up to Week 44) ]
Relapse is defined as depression (Montgomery-Åsberg Depression Rating Scale MADRS Score ≥22), or lack of efficacy as determined by the investigator.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2020)
  • Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 ]
    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 score indicates greater severity of symptoms. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. Mixed model for repeated measures (MMRM) was used for analyses.
  • Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed [ Time Frame: Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 ]
    The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participant who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness on the following scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. MMRM was used for analyses.
  • Clinical Global Impression Scale-Global Improvement Scale (CGI-I) Score [ Time Frame: Week 32 ]
    The CGI-I scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
  • Time From Randomization to Relapse of Major Depressive Disorder During the Entire 32-Week Double-Blind Treatment Period [ Time Frame: From date of double-blind randomization (Week 16) up to relapse or 32 weeks of Double-blind Period which occurs first (Up to Week 44) ]
    Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored. 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 ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The IQR was 25th percentile to 75th percentile.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2015)
  • Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Double-blind Baseline (Week 16) and Weeks 18, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    The change between MADRS total score at each week assessed or final visit and MADRS score at baseline in the double-blind period. 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 Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed [ Time Frame: Double-blind Baseline (Week 16) and Weeks 18, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
  • Clinical Global Impression Scale-Global Improvement Scale (CGI-I) score at Each Week Assessed in the double-blind period [ Time Frame: Weeks 18, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    The CGI-I 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.
  • Time From Randomization to Relapse of Major Depressive Disorder During the Entire 32-Week Double-Blind Treatment Period [ Time Frame: From date of double-blind randomization (Week 16) to relapse (up to Week 48) ]
    Relapse is defined as depression (Montgomery-Asberg Depression Rating Scale (MADRS Score ≥22), or lack of efficacy as determined by the investigator.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Phase 4, Relapse Prevention Study Evaluating the Efficacy and Safety of Vortioxetine (5, 10 and 20 mg) in Adults With Major Depressive Disorder
Brief Summary The purpose of this study is to evaluate the efficacy of vortioxetine (5, 10, and 20 mg) versus placebo during the first 28 weeks of the 32-week double-blind treatment period in the prevention of relapse in participants with MDD who responded to acute treatment with vortioxetine 10 mg.
Detailed Description

The drug being tested in this study is called vortioxetine. Vortioxetine is being tested for the prevention of relapse in adults with major depressive disorder (MDD) who respond to daily treatment with vortioxetine. This study will look at relapse rates of MDD in people who take vortioxetine.

The study will enroll approximately 1100 participants. All participants will receive vortioxetine 10 mg open-label for the first 16 weeks of the study. Participants who meet the appropriate MDD response criteria from the Week 8 Visit through Week 16 Visit will be eligible for randomization into the double-blind treatment period. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

  • Vortioxetine 5 mg
  • Vortioxetine 10 mg
  • Vortioxetine 20 mg
  • Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient

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

This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 55 weeks. Participants will make 19 visits to the clinic, and will be contacted by telephone 4 weeks after last dose of study drug for a follow-up assessment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: Vortioxetine
    Vortioxetine capsules
    Other Name: LuAA21004
  • Drug: Placebo
    Vortioxetine placebo-matching capsules
Study Arms  ICMJE
  • Experimental: Open-label: Vortioxetine 10 mg
    Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period.
    Intervention: Drug: Vortioxetine
  • Placebo Comparator: Double-blind: Placebo
    Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
    Intervention: Drug: Placebo
  • Experimental: Double-blind: Vortioxetine 5 mg
    Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
    Intervention: Drug: Vortioxetine
  • Experimental: Double-blind: Vortioxetine 10 mg
    Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
    Intervention: Drug: Vortioxetine
  • Placebo Comparator: Double-blind: Vortioxetine 20 mg
    Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
    Intervention: Drug: Vortioxetine
Publications * Not Provided

*   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: April 3, 2020)
1106
Original Estimated Enrollment  ICMJE
 (submitted: February 20, 2015)
1100
Actual Study Completion Date  ICMJE April 25, 2019
Actual Primary Completion Date March 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
  2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
  3. Suffers from recurrent major depressive disorder (MDD) as the primary diagnosis according to Diagnostic & Statistical Manual of Mental Disorders, 4th Edition - Text Revision (DSM-IV-TR) criteria (classification code 296.3x), and the current episode is confirmed by the Mini International Neuropsychiatric Interview (MINI).
  4. Reported duration of the current episode is ≥8 weeks and ≤18months.
  5. Had at least 2 other major depressive episodes (MDEs) before the current episode.
  6. Has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26 at the Screening and Baseline I visits.
  7. Is a man or woman aged 18 to 75 years, inclusive.
  8. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study and for 30 days after the last dose.

Exclusion Criteria:

  1. Has received any investigational compound within 30 days prior to screening or 5 half-lives prior to screening, whichever is longer.
  2. Has previously or is currently participating in this study.
  3. Has participated in 2 or more clinical studies in the year prior to screening, or has participated in a clinical trial for a psychiatric condition that is exclusionary per this protocol.
  4. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
  5. Has one or more of the following:

    1. Any current psychiatric disorder which is the primary focus of treatment other than MDD as defined in the DSM-IV-TR, and assessed by the MINI.
    2. Current or history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including schizoaffective disorder, major depression with psychotic features, bipolar depression with psychotic features, obsessive compulsive disorder (OCD), mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
    3. Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in full and sustained remission for at least 3 months from the day of screening (Participant must also have negative urine drug screen at Screening and Baseline I.)
    4. Presence or history of a clinically significant neurological disorder (including epilepsy) as determined by the investigator.
    5. Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
    6. Any Axis II disorder as defined by DSM-IV-TR that might compromise the study.
  6. 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.
  7. Has a history of lack of response to previous adequate treatment with vortioxetine for any MDD episode with adequate treatment considered to be known dose of vortioxetine in the approved recommended dose range for at least 6 weeks duration.
  8. Has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
  9. Has started receiving formal cognitive or behavioral therapy, systematic psychotherapy within 30 days from screening or plans to initiate such therapy during the study (supportive therapy, marital therapy and bereavement counseling are allowed).
  10. Has a significant risk of suicide according to the investigator's clinical judgment or has a score ≥5 on item 10 (suicidal thoughts) of the MADRS or has made a suicide attempt in the previous 6 months.
  11. Is required to take excluded medications or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study.
  12. 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 protocol fibromyalgia, obstructive sleep apnea, chronic pain diagnosis, and morbid obesity (BMI of > 40) are considered unstable due to the potential impact on assessment of the primary endpoint.

  13. Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.
  14. Has 1 or more laboratory value 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; or the participant 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 serum total bilirubin value >1.5 xULN.
    3. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2 xULN.
  15. Has glycosylated hemoglobin (HbA1C) ≥7% at screening and no prior diagnosis of diabetes and/or treatment for diabetes. NOTE: Participants with known stable diabetes are not excluded.
  16. Has a thyroid stimulating hormone (TSH) value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator. NOTE: Free T4 will be checked if TSH is out of range. If free T4 is abnormal the participant will be excluded.
  17. Has clinically significant abnormal vital signs as determined by the investigator.
  18. Has an abnormal electrocardiogram (ECG) as determined by the central reader and confirmed as clinically significant by the investigator.
  19. Is positive for Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, or has a history of human immunodeficiency virus (HIV) infection.
  20. Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability or efficacy.
  21. The participant, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
  22. Has a history of hypersensitivity or allergies to vortioxetine.
  23. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
  24. The participant is considered to be treatment resistant, eg, the participant has not responded to adequate monotherapy treatments of at least 6 weeks' duration, or has only responded to combination or augmentation therapy.
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 NCT02371980
Other Study ID Numbers  ICMJE LuAA21004_402
U1111-1161-4956 ( Registry Identifier: WHO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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 April 2020

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