An Efficacy and Safety Study of Lu AA21004 in Treating Generalized Anxiety Disorder

• The least squares mean change from Baseline in Hamilton Anxiety Scale total score at each week assessed. [ Time Frame: At all visits. ] [ Designated as safety issue: No ]
• Response rates at Week 8, with response defined as a ≥50% decrease in the HAM-A 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-Severity of Illness and Hospital Anxiety and Depression anxiety subscale. [ Time Frame: At all visits. ] [ Designated as safety issue: No ]
• The least squares mean change from Baseline in Clinical Global Impression Scale-Global Improvement. [ Time Frame: At all visits. ] [ Designated as safety issue: No ]
• Sheehan Disability Scale. [ Time Frame: Weeks: 1, 2, 4 and 8. ] [ Designated as safety issue: No ]
• Medical Outcomes Study 36-Item Short-Form Health Survey. [ Time Frame: Weeks: 2, 4 and 8. ] [ Designated as safety issue: No ]
• Health care resource utilization as assessed by the Health Economic Assessment Questionnaire [ Time Frame: Week: 8. ] [ Designated as safety issue: No ]

• The least squares mean change from Baseline in Hamilton Anxiety Scale total score at each week assessed. [ Time Frame: Week 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 HAM-A total score from Baseline. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Remission rates at Week 8, with remission defined as a Hamilton Anxiety Scale total score ≤7. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• The least squares mean change from Baseline in Clinical Global Impression Scale-Severity of Illness and Hospital Anxiety and Depression anxiety subscale. [ Time Frame: Weeks 0, 1, 2, 4, 6 and 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 ]
• Sheehan Disability Scale. [ Time Frame: Week 0, 1, 2, 4 and 8. ] [ Designated as safety issue: No ]
• Medical Outcomes Study 36-Item Short-Form Health Survey. [ Time Frame: Week 0, 2, 4 and 8. ] [ Designated as safety issue: No ]
• Health care resource utilization as assessed by the Health Economic Assessment Questionnaire [ Time Frame: Week 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 treating Generalized Anxiety Disorder.

Generalized anxiety disorder is associated with considerable personal stress as well as substantial social and functional impairment. It is characterized by excessive anxiety and uncontrollable worry that persist for longer than 6 months. Typically these worries are related to activities that are common to daily life events. Furthermore, patients with generalized anxiety disorder suffer from at least 3 of the following symptoms: restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and impaired sleep cycle. Patients with generalized anxiety disorder also suffer from many somatic symptoms such as palpitation, fast pulse, sweating, dyspnea, pain, nausea, dry mouth, and dizziness. Generalized anxiety disorder affects about 6.8 million American adults, including twice as many women as men. The disorder develops gradually and can begin at any point in the life cycle, although years of highest risk are between childhood and middle age. There is evidence that genes play a modest role in the disorder. About 12% of the patients in anxiety disorder clinics have generalized anxiety disorder, making it the most common diagnosis. In comparison with other anxiety disorders, generalized anxiety disorder is 4 times more prevalent than panic disorder and 3 times more prevalent than simple phobia. An estimate one-third of people with generalized anxiety disorder have no other comorbid diagnosis.

Lu AA21004 is a compound under development by Takeda Pharmaceutical Company Limited and H. Lundbeck A/S for the treatment of generalized anxiety disorder. Lu AA21004 combines serotonin enhancement with 5-hydroxytryptamine-1A partial agonism and affinity for the 5-hydroxytryptamine-3 receptor.

This aim of this phase 3 study is to investigate the efficacy and safety of a fixed dose of 5 mg Lu AA21004 QD in the treatment of generalized anxiety disorder.

• Drug: Lu AA21004
  Lu AA21004 5 mg, tablets, orally, once daily for up to 8 weeks.
• Drug: Placebo
  Lu AA21004 placebo-matching tablets, orally, once daily for up to 8 weeks.

• Experimental: Lu AA21004 5 mg QD
  Intervention: Drug: Lu AA21004
• Placebo Comparator: Placebo QD
  Intervention: Drug: Placebo

Inclusion Criteria:

• Has a primary diagnosis of Generalized Anxiety Disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR®) criteria.
• Has a Hamilton Anxiety Scale total score greater than or equal to 20 at Screening and Baseline.
• Has a Hamilton Anxiety Scale score greater than or equal to 2 on both Item 1 (anxious mood) and Item 2 (tension) at Screening and Baseline.
• Has a Montgomery-Åsberg Depression Rating Scale total score less than or equal to 16 at Screening and Baseline.

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.
• Is taking excluded medications.
• 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.
• 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.
• Has an alanine aminotransferase, aspartate aminotransferase, or total bilirubin level greater than 1.5 times the upper limit of normal.
• Has a serum creatinine of greater than 1.5 times the 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 at Screening and is deemed clinically significant by the investigator.
• Has an abnormal electrocardiogram.