Primary Outcome Measures:
- The least squares mean change from Baseline in the 14-item Hamilton Anxiety Scale total score after 8 weeks of treatment. [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- The least squares mean change from Baseline in item 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 item 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 Scale. [ 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 Scale. [ 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 ]
- Medical Outcomes Study 36-Item Short-Form Health Survey. [ Time Frame: Weeks 0, 2, 4 and 8. ] [ Designated as safety issue: No ]
- Health care resource utilization as assessed by the Health Economic Assessment Questionnaire. [ Time Frame: Weeks 0 and 8. ] [ Designated as safety issue: No ]
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 estimated one-third of people with generalized anxiety disorder have no other comorbid diagnosis.
Antidepressants effectively treat both anxiety and comorbid anxiety depression and there is a growing body of evidence that points to a continuum of disease in which anxiety and depression are considered different phenotypic expressions with a shared underlying neurochemical imbalance.
Lu AA21004 is a novel compound under development by Takeda Pharmaceutical Company Limited and H. Lundbeck A/S with clinical development for the treatment of generalized anxiety disorder. Lu AA21004 combines serotonin enhancement with 5-HT1A partial agonism with a high affinity for the 5-HT3 receptor.
Subjects participating in this study will be randomized to receive 5 mg of Lu AA21004 or a placebo once daily for 8 weeks. Subjects will be seen weekly during the first 2 weeks of treatment, then every 2 weeks up to the end of the 8-week treatment period. Subjects will also participate in a safety follow-up call 4 weeks after completion of the 8-week treatment.