A Safety and Efficacy Study of JNJ-42165279 in Participants With Social Anxiety Disorder

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy of JNJ-42165279 during 12 weeks of treatment in participants with Social Anxiety Disorder (SAD).

Detailed Description
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This is a Phase 2a randomized (study drug assigned by chance), double-blind (neither the Investigator nor the participants know about the study intervention), placebo-controlled, parallel-group, multi-center study of JNJ-42165279 in participants with social anxiety disorder. Participants will receive 25 milligram (mg) JNJ-42165279 or matching placebo orally once-daily from Day 1 up to 12 weeks. Participants will primarily be assessed for the change from baseline in Liebowitz Social Anxiety Scale (LSAS) at Week 12. Safety will be monitored throughout the study.

Official Title
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A Phase 2a Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multi-center Study Investigating the Efficacy, Safety, and Tolerability of JNJ-42165279 in Subjects With Social Anxiety Disorder.

Conditions
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Phobic Disorders

Intervention / Treatment
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* Drug: JNJ-42165279
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have a primary DSM-5 diagnosis of Social anxiety disorder (SAD) except those with performance only as a specifier. Participants with a diagnosis of comorbid Generalized Anxiety Disorder (GAD) or Major Depressive Disorder (MDD) may be included if the Investigator considers SAD to be the predominant diagnosis. Participants with current or lifetime history of Attention deficit hyperactivity disorder (ADHD) and specific phobia may be included as well Must have a Liebowitz Social Anxiety Scale score greater than or equal (>=) 70 at Screening and Baseline Participants with a current episode of MDD must have a HDRS17 total score less than or equal to (<=) 18 Must have a body mass index (BMI) between 18 and 35 kilogram per meter square (kg/m^2), inclusive, at screening Female participants must be either postmenopausal or surgically sterile Exclusion Criteria: Participants who have performance only SAD are excluded. Participants with other current significant psychiatric condition(s) (Axis 1 under DSM-IV), including, but not limited to, MDD with psychotic features (lifetime), bipolar disorder (including lifetime diagnosis), obsessive-compulsive disorder, borderline personality disorder, eating disorder (e.g., bulimia, anorexia nervosa), autism spectrum disorders, post-traumatic stress disorder (PTSD) or schizophrenia are excluded. Participants with a diagnosis of comorbid GAD or MDD may be included Participants is currently receiving specific psychotherapy for SAD Has a history of more than two unsuccessful adequate pharmacological treatment trials for SAD, defined as lack of response to at least 10 weeks of treatment at adequate doses (e.g., paroxetine >= 40 milligram per day (mg/day) or its equivalent; or clonazepam >= 2.5 mg/day or its equivalent) Concurrent use of psychotropic medications has a history of or current thyroid disease, thyroid dysfunction and is currently untreated for it

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-42165279<br>Participants will receive 25 milligram (mg) JNJ-42165279 orally once-daily from Day 1 up to 12 weeks. | Drug: JNJ-42165279<br>* Participants will receive 25 milligram (mg) JNJ-42165279 orally once-daily from Day 1 up to 12 weeks.<br>|
| Placebo Comparator: Placebo<br>Participants will receive a matching placebo orally once-daily from Day 1 up to 12 weeks. | Drug: Placebo<br>* Participants will receive a matching placebo orally once-daily from Day 1 up to 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Liebowitz Social Anxiety Scale (LSAS) Total Score | The LSAS is a 24-item, semi-structured interview on the severity of Social Anxiety Disorder. The LSAS separately assesses fear and avoidance of 24 social situations. The scale is divided into 2 subscales, 13 situations concerning performance anxiety, and 11 situations pertaining to social situations. The 24 items are first rated on a Likert Scale from 0 to 3 on fear felt during the situations (0=none, 1=mild, 2=moderate, 3= severe), and then the same items are rated regarding avoidance of the situation (0=never, 1=occasionally, 2=often, 3=usually) with higher scores indicating greater social anxiety. The LSAS fear/anxiety and avoidance subscale was calculated by summing the 24 fear/anxiety and avoidance item scores of the LSAS, and ranges from 0 to 72. Combining the total scores for the Fear and Avoidance sections provides an overall score with a maximum of 144 points and a minimum of 0 points. Higher scores indicated higher probability of social anxiety disorder (SAD). | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in LSAS Fear/Anxiety and Avoidance Subscales | The LSAS is a 24-item, semi-structured interview on the severity of Social Anxiety Disorder. The LSAS separately assesses fear and avoidance of 24 social situations. The scale is divided into 2 subscales, 13 situations concerning performance anxiety, and 11 situations pertaining to social situations. The 24 items are first rated on a Likert Scale from 0 to 3 on fear felt during the situations (0=none, 1=mild, 2=moderate, 3= severe), and then the same items are rated regarding avoidance of the situation (0=never, 1=occasionally, 2=often, 3=usually). Combining the total scores for the Fear and Avoidance sections provides an overall score with a maximum of 144 points and a minimum of 0 points. Higher scores indicated higher probability of SAD. The LSAS fear/anxiety and avoidance subscale was calculated by summing the 24 fear/anxiety and avoidance item scores of the LSAS, and ranges from 0 to 72. | Baseline and Week 12 | 
| Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Improvement From Baseline (Responders) on LSAS Total Score | Responders are participants with >= 50% improvement from baseline. The LSAS scale consists of 24 items which are divided into 2 subscales that address social interactional (11 items) and performance (13 items) situations. The 24 items are first rated on a Likert Scale from 0 to 3 on fear felt during the situations (0=none, 1=mild, 2=moderate, 3= severe), and then the same items are rated regarding avoidance of the situation (0=never, 1=occasionally, 2=often, 3=usually) with higher scores indicating greater social anxiety. The LSAS fear and avoidance subscale was calculated by summing the 24 fear/anxiety and avoidance item scores of the LSAS, and ranges from 0 to 72. Combining the total scores for the Fear and Avoidance sections provides an overall score with a maximum of 144 points and a minimum of 0 points. Higher scores indicated higher probability of SAD. | Week 12 | 
| Percentage of Participants With >=30% Improvement From Baseline (Remitters) on LSAS Total Score | Remitters are participants with >= 30% improvement from baseline on LSAS total score. The LSAS scale consists of 24 items which are divided into 2 subscales that address social interactional (11 items) and performance (13 items) situations. The 24 items are first rated on a Likert Scale from 0 to 3 on fear felt during the situations (0=none, 1=mild, 2=moderate, 3= severe), and then the same items are rated regarding avoidance of the situation (0=never, 1=occasionally, 2=often, 3=usually) with higher scores indicating greater social anxiety. The LSAS fear and avoidance subscale was calculated by summing the 24 fear/anxiety and avoidance item scores of the LSAS, and ranges from 0 to 72. Combining the total scores for the Fear and Avoidance sections provides an overall score with a maximum of 144 points and a minimum of 0 points. Higher scores indicated higher probability of SAD. | Week 12 | 
| Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) Total Score | The SIGH-A was included to determine the frequency and severity of signs and symptoms of anxiety, including participants with comorbid generalized anxiety disorders (GAD) and major depressive disorder (MDD), and determine both their influence on treatment and their responsiveness to treatment. The SIGH-A scale consists of 14 items with a score of 0 to 4. Higher scores indicated higher severity (0-absent, 1-mild, 2-moderate, 3-severe, 4-incapacitating). The SIGH-A total score was calculated by summing the 14 item scores, and ranges from 0 to 56. Higher scores indicated worse results. | Baseline and Week 12 | 
| Change From Baseline in Hamilton Anxiety Scale (HAM)-A6 Score | The HAM-A6 is a 6-item subscale derived from the original Hamilton Anxiety scale (HAM-A). It comprises of five psychic anxiety symptoms: anxious mood, psychic tension, fears, intellectual disturbances, and anxious behavior observed at the interview, as well as one somatic item, muscular tension. Each of the 6 items is rated by the clinician on a 5-point scale ranging from 0 (not present) to 4 (maximum degree). The HAM-A6 score was calculated by summing the 6 item scores, and ranges from 0 to 24. Higher scores indicated greater severity of symptoms. | Baseline and Week 12 | 
| Change From Baseline in Hamilton Depression Rating Scale (HDRS)-17 Total Score | The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition. | Baseline and Week 12 | 
| Change From Baseline in HDRS17 Anxiety/Somatization Factor Total Score | The HDRS17 anxiety/somatization factor derived from Cleary and Guy's factor analysis of the HDRS17 scale, includes six items from the original 17-item version: the items for psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Each of these items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). HDRS17 anxiety/somatization factor total score was calculated as the sum of the 6 item scores ranging from 0 to 18. Higher scores indicated greater severity of symptoms. | Baseline and Week 12 | 
| Change From Baseline in HAM-D6 Total Score | A 6-item subscale from the HDRS17 (HAM-D6) was analyzed as it had been shown to be a uni-dimensional scale that provided information to core depressive symptoms and was sensitive to treatment response. The six items were: depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and general somatics (tiredness and pains). Each of these items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). General somatics is scored 0 to 2 and all others are scored 0 to 4. The HAM-D6 total score was calculated by summing the 6 items scores, and ranges from 0 to 22. Higher scores indicated greater severity of core symptoms. | Baseline and Week 12 | 
| Percentage of Participants With Change From Baseline in Clinical Global Impression- Improvement (CGI-I) Score | The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The CGI-I is rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Percentage of participants with change from baseline (very much improved or much improved and Worsening or no change) in CGI-I score were reported. | Week 12 | 
| Percentage of Participants With >=50% Improvement From Baseline (Responders) in SIGH-A Total Score | Responders are participants with >= 50% improvement from baseline in SIGH-A total score. The SIGH-A scale consists of 14 items with a score of 0 to 4. Higher scores indicated higher severity (0-absent, 1-mild, 2-moderate, 3 severe, 4-incapacitating). The SIGH-A total score was calculated by summing the 14 item scores, and ranges from 0 to 56. Higher scores indicated worse results. | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Social Anxiety Disorder, JNJ-42165279