Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Vortioxetine; Placebo
Intervention description: Vortioxetine capsules; Vortioxetine placebo-matching capsules
Intervention MeSH terms: Vortioxetine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1106.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Drug therapy

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.
    

Eligibility 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 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.