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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02432703
• Collaborator: (none)
• Enrollment: 150
• Locations: 21
• Arms: 2
• Actual Duration (Months): 37.9
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Phobic Disorders	Drug: JNJ-42165279; Drug: Placebo	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: Jun 11, 2015
• Actual Primary Completion Date: Aug 9, 2018
• Actual Study Completion Date: Aug 9, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Liebowitz Social Anxiety Scale (LSAS) Total Score [Baseline and Week 12]

   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).

Secondary Outcome Measures

1. Change From Baseline in LSAS Fear/Anxiety and Avoidance Subscales [Baseline and Week 12]

   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.

2. Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Improvement From Baseline (Responders) on LSAS Total Score [Week 12]

   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.

3. Percentage of Participants With >=30% Improvement From Baseline (Remitters) on LSAS Total Score [Week 12]

   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.

4. Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) Total Score [Baseline and Week 12]

   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.

5. Change From Baseline in Hamilton Anxiety Scale (HAM)-A6 Score [Baseline and Week 12]

   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.

6. Change From Baseline in Hamilton Depression Rating Scale (HDRS)-17 Total Score [Baseline and Week 12]

   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.

7. Change From Baseline in HDRS17 Anxiety/Somatization Factor Total Score [Baseline and Week 12]

   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.

8. Change From Baseline in HAM-D6 Total Score [Baseline and Week 12]

   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.

9. Percentage of Participants With Change From Baseline in Clinical Global Impression- Improvement (CGI-I) Score [Week 12]

   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.

10. Percentage of Participants With >=50% Improvement From Baseline (Responders) in SIGH-A Total Score [Baseline, Week 12]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		La Jolla	California	United States
2		Hartford	Connecticut	United States
3		Orlando	Florida	United States
4		Chicago	Illinois	United States
5		Boston	Massachusetts	United States
6		Natick	Massachusetts	United States
7		New York	New York	United States
8		Rochester	New York	United States
9		Staten Island	New York	United States
10		Allentown	Pennsylvania	United States
11		Reading	Pennsylvania	United States
12		Dallas	Texas	United States
13		Salt Lake City	Utah	United States
14		Adelaide		Australia
15		Frankston		Australia
16		Melbourne		Australia
17		Perth		Australia
18		Edmonton	Alberta	Canada
19		Hamilton	Ontario	Canada
20		Mississauga	Ontario	Canada
21		Toronto	Ontario	Canada

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol - Aug 25, 2017
• Statistical Analysis Plan - Sep 17, 2018

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02432703
• Other Study ID Numbers: CR106641; 42165279SAX2001; 2014-004258-32
• First Posted: May 4, 2015
• Last Update Posted: Sep 2, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Social Anxiety Disorder; JNJ-42165279
• Additional relevant MeSH terms: Disease; Anxiety Disorders; Phobia, Social; Phobic Disorders; JNJ-42165279

Study Results

Participant Flow

Pre-assignment Detail	Among 150 participants, one participant was randomized by error. Only 149 participants received treatment and were included in the analysis.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Period Title: Overall Study
STARTED	75	74
COMPLETED	53	56
NOT COMPLETED	22	18

Baseline Characteristics

Arm/Group Title	Placebo	JNJ-42165279 25 mg	Total
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.	Total of all reporting groups
Overall Participants	75	74	149
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.4 (13.65)	38.3 (12.53)	37.8 (13.07)
Sex: Female, Male (Count of Participants)
Female	26 34.7%	26 35.1%	52 34.9%
Male	49 65.3%	48 64.9%	97 65.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 12%	13 17.6%	22 14.8%
Not Hispanic or Latino	66 88%	61 82.4%	127 85.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	8 10.7%	4 5.4%	12 8.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	15 20%	18 24.3%	33 22.1%
White	45 60%	50 67.6%	95 63.8%
More than one race	2 2.7%	1 1.4%	3 2%
Unknown or Not Reported	5 6.7%	1 1.4%	6 4%
Region of Enrollment (Count of Participants)
AUSTRALIA	11 14.7%	12 16.2%	23 15.4%
CANADA	14 18.7%	12 16.2%	26 17.4%
UNITED STATES	50 66.7%	50 67.6%	100 67.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Liebowitz Social Anxiety Scale (LSAS) Total Score
Description	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).
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Mean (Standard Deviation) [units on a scale]	-22.4 (23.57)	-29.4 (27.47)

2. Secondary Outcome

Title	Change From Baseline in LSAS Fear/Anxiety and Avoidance Subscales
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Fear/Anxiety	-10.7 (12.31)	-14.6 (13.65)
Avoidance	-11.7 (12.16)	-14.9 (14.45)

3. Secondary Outcome

Title	Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Improvement From Baseline (Responders) on LSAS Total Score
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Number [percentage of participants]	12.7 16.9%	18.6 25.1%

4. Secondary Outcome

Title	Percentage of Participants With >=30% Improvement From Baseline (Remitters) on LSAS Total Score
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Number [percentage of participants]	23.6 31.5%	42.4 57.3%

5. Secondary Outcome

Title	Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) Total Score
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Mean (Standard Deviation) [units on a scale]	-3.0 (6.20)	-4.2 (5.90)

6. Secondary Outcome

Title	Change From Baseline in Hamilton Anxiety Scale (HAM)-A6 Score
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Mean (Standard Deviation) [units on a scale]	-1.9 (3.32)	-2.3 (3.79)

7. Secondary Outcome

Title	Change From Baseline in Hamilton Depression Rating Scale (HDRS)-17 Total Score
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Mean (Standard Deviation) [units on a scale]	-0.9 (4.71)	-1.8 (3.99)

8. Secondary Outcome

Title	Change From Baseline in HDRS17 Anxiety/Somatization Factor Total Score
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Mean (Standard Deviation) [units on a scale]	-0.4 (2.25)	-0.9 (2.05)

9. Secondary Outcome

Title	Change From Baseline in HAM-D6 Total Score
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Mean (Standard Deviation) [units on a scale]	-0.7 (2.89)	-1.0 (2.56)

10. Secondary Outcome

Title	Percentage of Participants With Change From Baseline in Clinical Global Impression- Improvement (CGI-I) Score
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Very much improved or much improved	23.6 31.5%	44.1 59.6%
Worsening or no change	45.5 60.7%	35.6 48.1%

11. Secondary Outcome

Title	Percentage of Participants With >=50% Improvement From Baseline (Responders) in SIGH-A Total Score
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants who received at least 1 dose of the study agent (either placebo or JNJ-42165279), and had at least 1 assessment in the double-blind treatment phase on any of the efficacy parameters.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.	Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
Measure Participants	68	66
Number [percentage of participants]	47.3 63.1%	45.6 61.6%

Adverse Events

Time Frame	Up to 20 weeks
Adverse Event Reporting Description	Safety analysis set included all randomized participants who received at least one dose of study medication (either placebo or JNJ-42165279).
Arm/Group Title	Placebo		JNJ-42165279 25 mg
Arm/Group Description	Participants with social anxiety disorder (SAD) received matching placebo orally once daily for 12 weeks.		Participants with SAD received JNJ-42165279 25 milligrams (mg) orally once daily for 12 weeks.
All Cause Mortality
	Placebo		JNJ-42165279 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/74 (0%)
Serious Adverse Events
	Placebo		JNJ-42165279 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		2/74 (2.7%)
Immune system disorders
Anaphylactic Reaction	0/75 (0%)		1/74 (1.4%)
Psychiatric disorders
Alcohol Use Disorder	0/75 (0%)		1/74 (1.4%)
Other (Not Including Serious) Adverse Events
	Placebo		JNJ-42165279 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/75 (36%)		26/74 (35.1%)
Gastrointestinal disorders
Diarrhoea	2/75 (2.7%)		5/74 (6.8%)
Nausea	4/75 (5.3%)		0/74 (0%)
General disorders
Fatigue	3/75 (4%)		6/74 (8.1%)
Infections and infestations
Nasopharyngitis	6/75 (8%)		4/74 (5.4%)
Upper Respiratory Tract Infection	3/75 (4%)		5/74 (6.8%)
Nervous system disorders
Headache	13/75 (17.3%)		15/74 (20.3%)
Psychiatric disorders
Insomnia	6/75 (8%)		1/74 (1.4%)

Limitations/Caveats

The US food and drug administration placed a clinical hold on studies being conducted with fatty acid amide hydrolase (FAAH) inhibitor. When determined that serious adverse events were not related to FAAH inhibition, Janssen resumed this study in December 2016. At time of study suspension, an unblinded safety analysis was performed, and hence sample size was increased to replace participants who withdrew due to study suspension. Planned analyses were performed at time of final database lock.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation.