Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

A Randomized, Double-blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 3 Doses of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder

The purpose of this study is to determine the effectiveness and safety of vortioxetine, once daily (QD), in patients with Major Depressive Disorder.

The drug that was tested in this study is called vortioxetine. Vortioxetine is being tested to treat depression in adults who have major depressive disorder (MDD). This study looked at MDD relief in people who took varying dosages of vortioxetine.

The study enrolled 560 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

• Vortioxetine 1 mg
• Vortioxetine 5 mg
• Vortioxetine 10 mg
• Placebo (dummy inactive pill) - this was a capsule that looked like the study drug but had no active ingredient.

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

This multi-centre trial was conducted in Europe, Asia, Australia, and South Africa. The overall time to participate in this study was up to 14 weeks. Participants made 7 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.

Inclusion Criteria:

• Has a primary diagnosis of major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
• The reported duration of the current major depressive episode is at least 3 months.
• Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥26.
• A male or a female of childbearing potential who is sexually active agrees to use adequate contraception from Screening throughout the duration of the study and for 1 month after the last dose of study medication.

Exclusion Criteria:

• Has 1 or more the following:

  • Any current psychiatric disorder other than major depressive disorder as defined in the DSM-IV-TR.
  • Current or past history of: 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.
  • Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR. (must have negative urine drug screen prior to Baseline).
  • Presence or history of a clinically significant neurological disorder (including epilepsy).
  • Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).

• Has a significant risk of suicide according to the investigator's opinion or has a score ≥5 on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale, or has made a suicide attempt in the previous 6 months.

• Currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.

• Has a clinically significant unstable illness.

• Has previously failed to respond to adequate treatment with selective serotonin reuptake inhibitors and/or serotonin-norepinephrine reuptake inhibitors.

• Has received electroconvulsive therapy within 6 months prior to Screening.

• Has an alanine aminotransferase, aspartate aminotransferase, or total bilirubin level > 1.5 times the upper limit of normal.

• Has a serum creatinine of > 1.5 × upper limit of normal.

• Has a previous history of cancer that had been in remission for less than 5 years.

• Has thyroid stimulating hormone value outside the normal range.

• Has an abnormal electrocardiogram.