Efficacy of Lu AA21004 in Treating Generalized Anxiety Disorder

• The least squares mean change from Baseline in the Hamilton Anxiety Scale total score at each week assessed. [ Time Frame: Weeks 0, 1, 2, 4, 6 and 8. ] [ Designated as safety issue: No ]
• Response rates at Week 8, with response defined as a ≥50% decrease in the Hamilton Anxiety Scale total score from Baseline. [ Time Frame: Week 8. ] [ Designated as safety issue: No ]
• Remission rates at Week 8, with remission defined as a Hamilton Anxiety Scale total score ≤7. [ Time Frame: Week 8. ] [ Designated as safety issue: No ]
• The least squares mean change from Baseline in Clinical Global Impression Scale-Global Improvement. [ Time Frame: Weeks 1, 2, 4, 6 and 8. ] [ Designated as safety issue: No ]
• The least squares mean change from Baseline in Clinical Global Impression Scale-Severity of Illness. [ Time Frame: Weeks 0, 1, 2, 4, 6 and 8. ] [ Designated as safety issue: No ]
• The least squares mean change from Baseline in Hospital Anxiety and Depression Scale. [ Time Frame: Weeks 0, 1, 4 and 8. ] [ Designated as safety issue: No ]
• Sheehan Disability Scale. [ Time Frame: Weeks 0, 1, 2, 4 and 8. ] [ Designated as safety issue: No ]
• Healthcare resource utilization as assessed by the Health Economic Assessment Questionnaire. [ Time Frame: Weeks 0 and 8. ] [ Designated as safety issue: No ]

The purpose of this study is to determine the safety and efficacy of Lu AA21004, once daily (QD), in adults with generalized anxiety disorder.

Subjects participating in this study will be randomly assigned to receive either 2.5 mg, 5 mg or 10 mg of Lu AA21004 once daily, 60 mg of duloxetine once daily, or a placebo once daily for eight weeks.

Subjects 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. Subjects 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.

• Drug: Lu AA21004
  Lu AA21004 2.5 mg tablet, orally, once daily for up to 8 weeks.
• Drug: Lu AA21004
  Lu AA21004 5 mg tablet, orally, once daily for up to 8 weeks.
• Drug: Lu AA21004
  Lu AA21004 10 mg tablet, orally, once daily for up to 8 weeks.
• Drug: Placebo
  Lu AA21004 placebo-matching tablet, orally, once daily for up to 8 weeks.
• Drug: Duloxetine
  Duloxetine 60 mg tablet, orally, once daily for up to 8 weeks.

• Experimental: Lu AA21004 2.5 mg QD
  Intervention: Drug: Lu AA21004
• Experimental: Lu AA21004 5 mg QD
  Intervention: Drug: Lu AA21004
• Experimental: Lu AA21004 10 mg QD
  Intervention: Drug: Lu AA21004
• Placebo Comparator: Placebo QD
  Intervention: Drug: Placebo
• Active Comparator: Duloxetine 60 mg QD
  Intervention: Drug: Duloxetine

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. The subject 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:

• 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 subject 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 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.
• Has a history of lack of response to previous adequate treatment with duloxetine for any Generalized Anxiety Disorder episode.
• Has a thyroid stimulating hormone value outside the normal range.
• Has an abnormal electrocardiogram.