Efficacy Study of Lu AA21004 on Cognitive Dysfunction in Adult Patients With Major Depressive Disorder

• Cognitive dysfunction: Speed of processing, executive functioning [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  Change from baseline to Week 8 using the DSST (speed of processing, executive functioning)
• Cognitive dysfunction: Learning [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  Change from baseline to Week 8 using the RAVLT (learning)
• Cognitive dysfunction: memory [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  Change from baseline to Week 8 using the RAVLT (memory)
• To evaluate the safety and tolerability of 10 mg/day and 20 mg/day Lu AA21004 based on parameters such as adverse events, clinical safety laboratory tests and vital signs [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: Yes ]

Major Depressive Disorder (MDD) is a severe and common psychiatric disorder. Although MDD primarily involves mood disturbances, patients also usually present alterations in cognitive function (attention, memory, executive functioning and psychomotor speed). Even though antidepressants are suggested in the literature to potentially improve cognitive dysfunction in patients with MDD to some degree, there is a lack of adequate and well-controlled studies to investigate this effect. This study will evaluate the efficacy, safety and tolerability of a new antidepressant Lu AA21004 versus placebo on cognitive dysfunction in adult patients with Major Depressive Disorder.

• Drug: Placebo
  Orally, once daily for 8 weeks
• Drug: Lu AA21004 10 mg
  Orally, once daily for 8 weeks
  Other Name: Vortioxetine
• Drug: Lu AA21004 10 mg
  Orally, once daily for 1 week
  Other Name: Vortioxetine
• Drug: Lu AA21004 20 mg
  Orally, once daily for 7 weeks
  Other Name: Vortioxetine

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: Lu AA21004 10 mg
  Intervention: Drug: Lu AA21004 10 mg
• Experimental: Lu AA21004 20 mg
  Interventions:

  • Drug: Lu AA21004 10 mg
  • Drug: Lu AA21004 20 mg

Inclusion Criteria:

• The patient is an inpatient in a psychiatric hospital or an outpatient at a psychiatric setting at the time of the study entry.
• The patient is diagnosed with recurrent MDD according to DSM-IV-TR™ criteria (classification code 296.3x). The current MDE should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
• The patient has received prescribed treatment for a previous episode of depression.
• The patient has a MADRS total score ≥26.
• The reported duration of the current MDE is at least 3 months.

Exclusion Criteria:

• The patient has a score ≥70 on the DSST (numbers correct), ≥42 on the RAVLT (learning) and ≥14 on the RAVLT (memory) at the Baseline Visit.
• The patient has any current Axis I disorder (DSM-IV-TR™ criteria) other than MDD, confirmed using the MINI.
• The patient has a current diagnosis or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features.
• The patient suffers from personality disorders, mental retardation, pervasive development disorder, attention-deficit/hyperactivity disorder, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
• The patient has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
• The patient is diagnosed with reading disability (dyslexia).
• The patient is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide <6 months prior to the Screening Visit.
• The patient has received electroconvulsive therapy <6 months prior to the Screening Visit.
• 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.
• The patient 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.
• The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for >5 years prior to the first drug dose.

• The patient has a clinically significant unstable illness, for example:

  • cardiovascular disease
  • seizure disorder or encephalopathy
  • congestive heart failure
  • cardiac hypertrophy
  • arrhythmia
  • bradycardia (pulse <50 bpm)
  • respiratory disease
  • hepatic impairment or renal insufficiency
  • metabolic disorder
  • endocrinological disorder
  • gastrointestinal disorder
  • haematological disorder
  • infectious disorder
  • any clinically significant immunological condition
  • dermatological disorder
  • venereal disease
• The patient has, at the Screening Visit, an abnormal ECG that is, in the investigator's opinion, clinically significant.
• The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.
• The patient has previously been exposed to Lu AA21004.

Other inclusion and exclusion criteria may apply.