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

This study is currently recruiting participants.
Verified August 2017 by Takeda
Sponsor:
ClinicalTrials.gov Identifier:
NCT02371980
First Posted: February 26, 2015
Last Update Posted: August 4, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Takeda
  Purpose
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 major depressive disorder (MDD) who responded to acute treatment with vortioxetine 10 mg.

Condition Intervention Phase
Major Depressive Disorder Drug: Vortioxetine Drug: Placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 228
Actual Study Start Date: February 18, 2015
Estimated Study Completion Date: February 1, 2019
Estimated Primary Completion Date: January 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-label: Vortioxetine 10 mg
Vortioxetine 10 mg, capsules, orally, once, daily Week 1 through Week 16.
Drug: Vortioxetine
Vortioxetine capsules
Other Name: LuAA21004
Experimental: Double-blind: Vortioxetine 5 mg
Vortioxetine 5 mg, capsules, orally, once, daily, Week 17 through Week 44.
Drug: Vortioxetine
Vortioxetine capsules
Other Name: LuAA21004
Experimental: Double-blind: Vortioxetine 10 mg
Vortioxetine 10 mg, capsules, orally, once, daily, Week 17 through Week 44.
Drug: Vortioxetine
Vortioxetine capsules
Other Name: LuAA21004
Experimental: Double-blind: Vortioxetine 20 mg
Vortioxetine 20 mg, capsules, orally, once, daily, Week 17 through Week 44.
Drug: Vortioxetine
Vortioxetine capsules
Other Name: LuAA21004
Placebo Comparator: Double-blind: Placebo
Vortioxetine placebo-matching capsules, orally, once, daily, Week 17 through Week 44.
Drug: Placebo
Vortioxetine placebo-matching capsules

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.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 subject is considered to be treatment resistant, eg, the subject has not responded to adequate monotherapy treatments of at least 6 weeks' duration, or has only responded to combination or augmentation therapy.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02371980


Contacts
Contact: Takeda Study Registration Call Center +1-877-825-3327 medicalinformation@tpna.com

  Show 76 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Clinical Science Takeda
  More Information

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02371980     History of Changes
Other Study ID Numbers: LuAA21004_402
U1111-1161-4956 ( Registry Identifier: WHO )
First Submitted: February 20, 2015
First Posted: February 26, 2015
Last Update Posted: August 4, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:
Drug therapy

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