Exploratory Study to Evaluate the Effect of SYN111 (Rufinamide) in Patients With Generalized Anxiety Disorder (GAD)

Study Overview
=================
Brief Summary
-----------------
A Multi-Centered Randomized, Double-Blind, Placebo-Controlled, Phase 2, Exploratory Study to Evaluate the Effect of Rufinamide on Anxiety in Patients with Moderate to Severe Generalized Anxiety Disorder.

Detailed Description
-----------------
This was an exploratory study to evaluate the effect of 500 or 1000 mg per day for 8 weeks of Rufinamide compared to placebo on measures of anxiety in patients with Generalized Anxiety Disorder, and to determine tolerability of Rufinamide in this population.

Official Title
-----------------
A Multi-Center,Randomized, Double-Blind, Placebo-Controlled, Phase 2, Exploratory Study to Evaluate the Effect of Rufinamide on Anxiety in Patients With Moderate to Severe Generalized Anxiety Disorder

Conditions
-----------------
Generalized Anxiety Disorder

Intervention / Treatment
-----------------
* Drug: SYN111
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Outpatient 18-65 Meet Diagnostic and Statistical Manual,(DSM) IV criteria for GAD Have moderate to severe anxiety Sign IRB (Institutional Review Board) approved consent and can comply with visits and procedures Women of childbearing potential must use acceptable method of contraception Exclusion Criteria: Have diagnosis of adjustment disorder or anxiety disorder Not otherwise specified (NOS) Have diagnosis of specific phobia Have diagnosis of antisocial personality disorder or other Axis II Disorder Have diagnosis of substance abuse disorder within 3 months of study entry Have diagnosis of major depressive disorder or panic disorder within 6 months of study entry Have diagnosis of PTSD, eating disorder substance dependence disorder within 12 months of study entry Have diagnosis anytime during lifetime of schizophrenia or other psychotic disorder, bipolar mood disorder, Obsessive-Compulsive Disorder (OCD), psychosurgery Require medication to treat GAD other than study medication Failed to show improvement with past treatment for GAD Excessively consume caffeine Are receiving treatment with prohibited medications Uncontrolled thyroid condition Positive urine drug screen Obese Clinically significant ECG finding Participating in other clinical trial Clinically significant out of range lab value Past exposure to rufinamide Pregnant or nursing females

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SYN111<br>500 mg 1 week, followed by 1000 mg for 7 weeks | Drug: SYN111<br>* 500 mg for 1 week followed by 1000 mg for 7 weeks<br>* Other names: Rufinamide;|
| Placebo Comparator: Placebo<br>0 mg tablets | Drug: Placebo<br>* 0 mg tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hamilton Anxiety Scale (HAMA) - Total Score: Summary Statistics - Observed | The Hamilton Anxiety Scale is a 14-item test measuring the severity of anxiety symptoms. It provides measures of overall anxiety, psychic anxiety (mental agitation and psychological distress), and somatic anxiety (physical complaints related to anxiety). The interviewer then rated the individuals on a 5-point scale for each of the 14 items. Seven of the items specifically address psychic anxiety and the remaining 7 items address somatic anxiety. The total anxiety score ranges from 0 to 56. The 7 psychic anxiety items elicit a psychic anxiety score that ranges from 0 to 28. The remaining 7 items yield a somatic anxiety score that also ranges from 0 to 28. A score of 17 or less indicates mild anxiety severity. A score from 18 to 24 indicates mild to moderate anxiety severity, a score of 25 to 30 indicates a moderate to severe anxiety and lastly a score of 31-56 is very severe. HAM-A total score is the sum of items 1 - 14. | 8 Weeks | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS). Summary Statistics | The Hospital Anxiety and Depression Scale is a self screening questionnaire for depression and anxiety. It consists of 14 questions, seven for anxiety and seven for depression. The 14 statements are relevant to either generalized anxiety (7 statements) or 'depression' (again 7). Each question has 4 possible responses. Responses are scored on a scale from 3 to 0. The maximum score is therefore 21 for depression and 21 for anxiety. A score of 11 or higher indicates the probable presence of the mood disorder with a score of 8 to 10 being just suggestive of the presence of the respective state. The 2 subscales, anxiety and depression, have been found to be independent measures. In its current form the HADS is now divided into 4 ranges: normal (0-7), mild (8-10), moderate (11-15) and severe (16-21). Anxiety score = sum of items 1, 3, 5, 7, 9, 11, and 13. Depression score = sum of items 2, 4, 6, 8, 10, 12, and 14. | 8 Weeks | 
| Change From Baseline in Montgomery-Asberg Depression Scale (MADRS) Summary Statistics. | The MADRS (Montgomery and Asberg 1979) is a clinician-rated instrument that measures the presence and severity of depression. This instrument consists of 10 items. Each item is rated on a defined step scale of 0 to 6 with anchors at 2-point intervals. The MADRS total score is the sum of the 10 items and ranges from 0 to 60. A high numeric rating shows a greater degree of symptom severity. | 8 Weeks | 
| Change From Baseline in Clinical Global Impression Scale for Severity of Illness: (CGI-S) | Severity of illness is the first scale in the CGI. A rating is filled in by the investigator at the start of treatment based on a 0-7 point weighted scale. It goes from not assessed (0), to among the most extremely ill patients (7). | 8 weeks | 
| Change From Baseline Raskin Depression Scale. | It explores the extent to which an individual demonstrates depression on three sub-scales (rated 1-5): verbal self-report, behavior and secondary symptoms of depression. Scores range from 3-15, with higher scores indicating greater severity. | 8 weeks | 
| Change From Baseline in Covi Anxiety Scale (CAS) - Index Total Score: Summary Statistics Observed | The Covi Anxiety Scale is a simple 3 item scale for the assessment of severity of anxiety symptoms. The scale measures 3 dimensions: verbal report, behavior and somatic symptoms of anxiety. Each item scored on a scale of 1 - 5. (1)not at all, (2)somewhat, (3)moderately, (4) considerably, and (5)very much), hence the scale is a 5- to 15 point range. The three items are the patient's verbal report (feeling shaky, jittery, jumpy), observed behavior consistent with anxiety during the interview (e.g. appearing frightened, shaky, restless) and somatic complains (e.g., sweating, trembling, heart pounding). COVI Rating Scale total score is the sum of items 1 - 3. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GAD