Efficacy of Lu AA21004 on Cognitive Dysfunction in Major Depressive Disorder
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Cognitive Dysfunction
Intervention: vortioxetine (Lu AA21004); Duloxetine; Placebo
Intervention description: Lu AA21004 capsules; Duloxetine capsules; Placebo matching capsules
Intervention MeSH terms: Duloxetine Hydrochloride; Vortioxetine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 602.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the effects of Lu AA21004, once daily (QD), on
      cognitive dysfunction in patients with major depressive disorder.
    

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. The participant has recurrent MDD as the primary diagnosis according to Diagnostic and
             Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
             criteria (classification code 296.3x). The current MDE should be confirmed using the
             Mini International Neuropsychiatric Interview (MINI) V6.0.0.

          4. The participant has received prescribed treatment for a previous episode of
             depression.

          5. The participant has a MADRS total score ≥26 at both the screening and baseline visits.

          6. Participant reports subjective cognitive dysfunction (such as difficulty
             concentrating, slow thinking, and difficulty in learning new things or remembering
             things).

          7. The reported duration of the current major depressive episode (MDE) is at least 3
             months

          8. The participant is a man or woman between 18 and 65 years old, inclusive.

          9. 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
             completion of the study.

        Exclusion Criteria:

          1. The participant has previously participated in this study.

          2. The participant has a history of severe drug allergy or hypersensitivity, or known
             hypersensitivity to any of the excipients of the investigational medicinal product
             (IMP).

          3. The participant has known hypersensitivity to duloxetine.

          4. The participant has hereditary problems of fructose intolerance, glucose-galactose
             malabsorption, or sucrose-isomaltase insufficiency.

          5. The participant is an immediate family member, study site employee, or is in a
             dependent relationship with a study site employee who is involved in the conduct of
             this study (e.g., spouse, parent, child, sibling) or may consent under duress.

          6. The participant has a score ≥70 on the DSST (numbers correct) at the Baseline Visit.

          7. The participant is, in the opinion of the investigator, not able to complete the
             neuropsychological tests validly at the Baseline Visit.

          8. If female, the participant is pregnant or lactating or intending to become pregnant
             before, during, or within 30 days after participating in this study; or intending to
             donate ova during such time period.

          9. The participant has 1 or more of the following:

               1. Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR (as
                  assessed by the MINI Version 6.0.0).

               2. Current or history of attention deficit hyperactivity disorder (ADHD), pervasive
                  developmental disorder, 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. Current diagnosis of alcohol or other substance abuse or dependence (excluding
                  nicotine or caffeine) as defined in the DSM-IV-TR that has not been in sustained
                  full remission for at least 2 years prior to Screening. (Participant must also
                  have negative urine drug screen prior to Baseline).

               4. Presence or history of a clinically significant neurological disorder (including
                  epilepsy).

               5. Neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple
                  sclerosis, Huntington's disease, etc).

               6. Any DSM-IV Axis II disorder that might compromise the study.

         10. The participant has any other disorder for which the treatment takes priority over
             treatment of MDD or is likely to interfere with study treatment or impair treatment
             compliance.

         11. The participant has physical, cognitive, or language impairment of such severity as to
             adversely affect the validity of the data derived from the neuropsychological tests.

         12. The participant is diagnosed with reading disability (dyslexia).

         13. The participant 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.

         14. The participant, in the opinion of the investigator, poses a risk of harm to others.

         15. The participant has initiated formal cognitive or behavioral therapy, systemic
             psychotherapy within less than 6 months of study screening, or has plans to initiate
             such therapy during the study.

         16. The participant has received electroconvulsive therapy, vagal nerve stimulation, or
             repetitive transcranial magnetic stimulation within 6 months prior to Screening.

         17. The current depressive symptoms are considered by the investigator to have been
             resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each at
             the recommended dose.

         18. The participant has a history of moderate or severe head trauma (for example, loss of
             consciousness for more than 1 hour) or other neurological disorders or systemic
             medical diseases that are, in the opinion of the investigator, likely to affect
             central nervous system functioning.

         19. The participant has a previous history of cancer that had been in remission for less
             than 5 years prior to the first dose of investigational drug. This criterion does not
             include those participants with basal cell or stage I squamous cell carcinoma of the
             skin.

         20. The participant has a clinically significant unstable illness, for example, hepatic
             impairment or renal insufficiency, or cardiovascular, pulmonary, gastrointestinal,
             endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous
             tissue disorders, or metabolic disturbance.

             Note: For the purposes of this protocol, the following conditions are considered
             unstable due to the potential impact on assessment of MDD response and/or cognitive
             status: pain disorders, chronic fatigue syndrome, fibromyalgia, obstructive sleep
             apnea, and known cases of HIV, HBV, and HCV

         21. The participant has a known history of or currently has increased intraocular pressure
             or is at risk of acute narrow-angle glaucoma.

         22. The participant 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 evaluation period as specified in the Excluded
             Medications Section.

         23. The participant has received any investigational compound <30 days before Screening or
             5 half-lives prior to Screening.

         24. The participant has clinically significant abnormal vital signs as determined by the
             investigator.

         25. The subject has thyroid stimulating hormone (TSH) outside the normal range at the
             Screening Visit.

             Note: If TSH value is outside the normal range, a free T4 will be obtained. Subjects
             who have elevated TSH but normal T4 (i.e. subclinical hypothyroidism) will be
             excluded. For subjects who are on thyroid hormone replacement therapy, a lower TSH
             with normal T4, are eligible to participate in the study only if there are no clinical
             symptoms of hypothyroidism .

         26. The participant 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 total serum total bilirubin value >1.5×ULN.

               3. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value
                  >2×ULN.

         27. The participant has an abnormal electrocardiogram (ECG) as determined by the central
             reader and confirmed as clinically significant by the investigator.

         28. The participant has a disease or takes medication that, in the opinion of the
             investigator, could interfere with the assessments of safety, tolerability, or
             efficacy.

         29. The participant, in the opinion of the investigator, is unlikely to comply with the
             clinical study protocol or is unsuitable for any reason.

         30. The participant has been previously exposed to LuAA21004 compound.

         31. The participant has a history of lack of response to previous adequate treatment with
             duloxetine.