Efficacy of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Active-Referenced, Fixed-Dose Study Comparing the Efficacy and Safety of 3 Doses of Lu AA21004 in Acute Treatment of Adults With Generalized Anxiety Disorder

The purpose of this study is to determine the safety and efficacy of vortioxetine, once daily (QD), in adults with generalized anxiety disorder.

Participants in this study will be randomly assigned to receive either 2.5 mg, 5 mg or 10 mg of vortioxetine, once daily, 60 mg of duloxetine once daily, or a placebo once daily for eight weeks.

Participants will be seen weekly during the first 2 weeks of treatment, and then every 2 weeks up to the end of the 8-week treatment period. Participants who complete the 8-week treatment period will enter a 2-week discontinuation period in order to assess potential discontinuation symptoms. Total commitment time is up to 12 weeks.

Inclusion Criteria:

• Has a primary diagnosis of generalized anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR®) criteria (classification code 300.02).
• Has a Hamilton Anxiety Scale total score ≥ 20. Has a Hamilton Anxiety Scale score ≥2 on both item 1 (anxious mood) and item 2 (tension).
• Has a Montgomery-Åsberg Depression Rating Scale total score ≤16.

Exclusion Criteria:

• Had received any investigational compound <30 days before Screening or 5 half-lives prior to Screening, whichever is longer.

• Received Lu AA21004 in a previous clinical study.

• Was a study site employee, or an immediate family member (ie, spouse, parent, child, or sibling) of a study site employee involved in conduct of this study.

• Has 1 or more of the following:

  • Any current psychiatric disorder other than Generalized Anxiety Disorder as defined in the DSM-IV-TR® (as assessed by the Mini International Neuropsychiatric Interview [MINI]).
  • 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® and must have a 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).
  • Any Axis II disorder that might compromise the study.

• Has known sensitivity to duloxetine.

• Is taking excluded medications

• 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.

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

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

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

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

• 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.

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

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

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

• Hasclinically significant abnormal vital signs as determined by the investigator.

• Has a history of lack of response to previous adequate treatment with duloxetine for any Generalized Anxiety Disorder episode.

• Has 1 or more laboratory values outside the normal range, based on the blood or urine samples taken at the Screening Visit

• Has a thyroid stimulating hormone value outside the normal range.

• Has an abnormal electrocardiogram.

• has a disease or was taking medications that, in the opinion of the investigator, could have interfered with the assessments of safety, tolerability, or efficacy.

• The patient, in the opinion of the investigator, was unlikely to comply with the clinical study protocol or was unsuitable for any reason.

• Had previously been enrolled in this study.