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

A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Duloxetine-Referenced, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (15 and 20 mg) of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder

The purpose of this study is to evaluate the efficacy, safety and tolerability of vortioxetine, once daily (QD), compared with placebo in adults 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 614 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 15 mg
• Vortioxetine 20 mg
• Duloxetine 60 mg
• Placebo (dummy inactive capsule) - 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-center trial was conducted in the United States. The overall time to participate in this study was up to 13 weeks. Participants made 9 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:

1. Man or a woman who suffers from a major depressive episode (MDE) recurrent as the primary diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.3x) as confirmed by the Structured Clinical Interview for DSM Disorders (SCID).
2. The reported duration of the current MDE is at least 3 months.
3. Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.
4. Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.

Exclusion Criteria:

1. Has previously participated in a Lu AA21004 clinical study.

2. Has 1 or more the following:

   1. Any current psychiatric disorder other than major depressive disorder (MDD) as defined in the DSM-IV-TR (as assessed by the SCID).
   2. 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.
   3. Diagnosis of any substance abuse or dependence (except nicotine and caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least 2 years prior to screening (subject 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 disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
   6. Any Axis II disorder that might compromise the study.

3. 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. Has 1 or more laboratory values 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.

4. Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.

5. Has clinically significant abnormal vital signs as determined by the investigator.

6. Has an abnormal electrocardiogram as determined by the central reader and confirmed as clinically significant by the investigator.

7. Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal.

8. Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those patients with basal cell or Stage I squamous cell carcinoma of the skin.

9. Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.

10. Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.

11. Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. The following are also considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.

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