Efficacy and Safety of Vortioxetine (Lu AA21004) for Treatment of Generalized Anxiety Disorder in Adults.

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

The purpose of this study is to evaluate the efficacy and safety of vortioxetine, once daily (QD), in adults with Generalized Anxiety Disorders.

The drug that was tested in this study is called Vortioxetine. Vortioxetine is being tested to treat anxiety in adults who have general anxiety disorder (GAD). This study looked at GAD relief in people who took vortioxetine.

The study enrolled 301 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

• Vortioxetine 5 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-center trial was conducted in Europe. The overall time to participate in this study was up to 13 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:

• Suffers from a primary diagnosis of Generalized Anxiety Disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
• Has a Hamilton Anxiety Scale total score ≥20 at Screening and Baseline.
• Has a Hamilton Anxiety Scale score ≥2 on both Item 1 (anxious mood) and Item 2 (tension) at Screening and Baseline.
• Has a Montgomery-Åsberg Depression Rating Scale total score ≤16 at Screening and Baseline.
• Male and females of childbearing potential who are sexually active agree 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 received any investigational compound <30 days before Screening or 5 half-lives prior to Screening.

• Has received Lu AA21004 in a previous clinical study or as a therapeutic agent.

• Has 1 or more of the following:

  • Any current psychiatric disorder other than Generalized Anxiety 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.
  • Presence or history of a clinically significant neurological disorder (including epilepsy).
  • Neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington disease, etc).
  • Any Axis II disorder that might compromise the study.

• 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 including:

  • Nonsteroidal anti-inflammatory drugs
  • Rifampin
  • Macrolide antibiotics
  • Hormones
  • Hypoglycemic agents and Insulin
  • Systemic steroids
  • Antineoplastics
  • Antiobesity agents
  • Antidiarrheal agents (episodic use allowed)
  • Antifungal agents (episodic topical use allowed)
  • Antihistamines (episodic use of loratadine, desloratadine, cetirizine allowed)
  • Cough/cold agents (episodic use allowed but preparations containing pseudoephedrine and narcotics are NOT allowed)
  • Diuretics (episodic use allowed)

• 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 inhibitors 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 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 bilirubin level >1.5 times the upper limits of normal.

• Has a serum creatinine of >1.5 times the upper limits of normal.

• 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 participants with basal cell or stage I squamous cell carcinoma of the skin.

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

• Has 1 or more laboratory values outside the normal range, based on the blood or urine samples taken at Screening, that are considered by the investigator to be clinically significant.

• Has thyroid stimulating hormone value outside the normal range at Screening and is deemed clinically significant by the investigator.

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

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

• Has previously participated in this study.