An Efficacy, Safety and Tolerability Study of JNJ-42165279 in Participants With Major Depressive Disorder With Anxious Distress

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02498392
• Collaborator: (none)
• Enrollment: 161
• Locations: 32
• Arms: 4
• Actual Duration (Months): 40
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety and tolerability of JNJ-42165279 in participants with major depressive disorder (MDD) with anxiety symptoms who have had inadequate response to treatment with a selective serotonin reuptake inhibitor (SSRI) or serotonergic/noradrenergic reuptake inhibitor (SNRI).

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder; Anxiety	Drug: JNJ-42165279; Other: Placebo	Phase 2

Detailed Description

This is a multicenter, double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled, randomized, parallel-group study in participants with Major Depressive Disorder (MDD) with Anxious Distress. Participants who had treatment initiated with a SSRI/SNRI allowed by the protocol will be evaluated at the investigation site. The site assessment will be reviewed and validated by an independent central rater. The review will include the clinical history of MDD, SSRI/SNRI treatment of adequate dose and duration for the current episode of depression, and current symptom severity on the Hamilton Depression Rating Scale (HDRS17). Enrolled participants will be maintained on SSRI/SNRI treatment throughout the study to determine whether additional treatment with JNJ-4216579 can reduce the symptoms of MDD with anxious distress.The study will consist of 3 phases: a Screening Phase of up to 4 weeks, an 11-week double-blind Treatment Phase, and a 3-week post-treatment (follow up) Phase. The double-blind treatment Phase of the trial will consist of 3 periods. The first period is a placebo lead-in of double-blind duration, after which participants will enter the treatment period when they will be randomly assigned to JNJ-42165279 or continuation on placebo for 6 weeks. Participants who successfully complete the treatment period prior to the end of Week 11, will be treated with placebo for the remaining time of the double-blind phase of the study, which will vary depending on the duration of the placebo lead-in for the specific participant. The total study duration for each participant will be approximately 18 weeks. Efficacy and safety of JNJ-42165279 will be evaluated. Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 161 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 Major Depressive Disorder With Anxious Distress
• Actual Study Start Date: Oct 7, 2015
• Actual Primary Completion Date: Feb 4, 2019
• Actual Study Completion Date: Feb 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Responders-Placebo Participants who responded in the placebo lead-in period will be administered with Matching Placebo orally.	Other: Placebo; Matching Placebo will be administered orally.
Experimental: Responders-JNJ-42165279 Participants who responded in the placebo lead-in period will be administered with JNJ-42165279 orally at a dose of 25 milligrams (mg) tablets once daily for 6 weeks.	Drug: JNJ-42165279; JNJ-42165279 will be administered orally at a dose of 25 milligrams (mg) tablet once daily for 6 weeks.
Placebo Comparator: Non Responders-Placebo Participants who did not respond in the placebo lead-in period will be administered with Matching Placebo orally.	Other: Placebo; Matching Placebo will be administered orally.
Experimental: Non Responders-JNJ-42165279 Participants who did not respond in the placebo lead-in period will be administered with JNJ-42165279 orally at a dose of 25 mg tablets once daily for 6 weeks.	Drug: JNJ-42165279; JNJ-42165279 will be administered orally at a dose of 25 milligrams (mg) tablet once daily for 6 weeks.

Outcome Measures

Primary Outcome Measures

1. Double-blind Treatment Period: Change From Baseline in Hamilton Depression Rating Scale (HDRS17) Total Score at Week 6 (eITT Population) [Baseline and Week 6]

   HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.

2. Double-blind Treatment Period: Change From Baseline in HDRS17 Total Score at Week 6 (fITT Population) [Baseline and Week 6]

   HDRS17 is a clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of the 17 items is rated by clinician on either a 3-point (0 to 2) or a 5-point (0 to 4) scale which used a rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. HDRS17 total score is calculated as sum of 17 item scores and ranges from 0 to 52. For each item as well as the total score, higher scores indicate greater severity of depression.

Secondary Outcome Measures

1. Double-blind Treatment Period: Change From Baseline in Hamilton Anxiety Rating Subscale (HAM-A6) Score at Week 6 (eITT Population) [Baseline and Week 6]

   The HAM-A6 is a 6-item subscale derived from the original Hamilton Anxiety scale (HAM-A) which consists of 5 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.

2. Double-blind Treatment Period: Change From Baseline in HAM-A6 Score at Week 6 (fITT Population) [Baseline and Week 6]

   The HAM-A6 is a 6-item subscale derived from the original Hamilton Anxiety scale (HAM-A) which consists of 5 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.

3. Double-blind Treatment Period: Change From Baseline in Hamilton Depression Rating Subscale (HAM-D6) Score at Week 6 (eITT Population) [Baseline and Week 6]

   HAM-D6 is a 6-item subscale derived from HDRS17 and consists of depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and somatics symptoms (tiredness and pain), rated on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. 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 somatic is scored 0 to 2 and all others are scored 0 to 4. The HAM-D6 is calculated from summing the 6 items and the score ranges from 0 (normal) to 22 (severe), with higher scores indicating greater severity of core symptoms.

4. Double-blind Treatment Period: Change From Baseline in HAM-D6 Score at Week 6 (fITT Population) [Baseline and Week 6]

   HAM-D6 is a 6-item subscale derived from HDRS17 and consists of depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and somatic symptoms (tiredness and pain), rated on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. 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 somatic is scored 0 to 2 and all others are scored 0 to 4. The HAM-D6 is calculated from summing the 6 items and the score ranges from 0 (normal) to 22 (severe), with higher scores indicating greater severity of core symptoms.

5. Double-blind Treatment Period: Change From Baseline in Structured Interview Guide of the Hamilton Anxiety Scale (SIGH-A) Total Score at Week 6 (eITT Population) [Baseline and Week 6]

   The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety; 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, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.

6. Double-blind Treatment Period: Change From Baseline in SIGH-A Total Score at Week 6 (fITT Population [Baseline and Week 6]

   The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety; 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, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.

7. Double-blind Treatment Period: Change From Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (eITT Population) [Baseline and Week 6]

   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: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Each of 6 items is rated by clinician on either a 3-point (0 to 2) or a 5-point (0 to 4) scale with rating of 0:absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe and is calculated as sum of 6 item scores ranging from 0 to 18, with higher scores indicating greater severity of symptoms for each item as well as total score.

8. Double-blind Treatment Period: Change From Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (fITT Population) [Baseline and Week 6]

   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: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Each of 6 items is rated by clinician on either a 3-point (0 to 2) or a 5-point (0 to 4) scale with rating of 0:absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe and is calculated as sum of 6 item scores ranging from 0 to 18, with higher scores indicating greater severity of symptoms for each item as well as total score.

9. Double-blind Treatment Period: Percentage of Participants With Greater Than or Equal to (>=) 30 Percent (%) Improvement on the HDRS17 Total Score at Week 6 (eITT Population) [Week 6]

   Percentage of participants who had >=30% improvement (responders) on HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.

10. Double-blind Treatment Period: Percentage of Participants With >= 30 % Improvement on the HDRS17 Total Score at Week 6 (fITT Population) [Week 6]

    Percentage of participants who had >=30% improvement (responders) on HDRS17 total score at Week 6 was reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.

11. Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement in the HDRS17 Total Score at Week 6 (eITT Population) [Week 6]

    Percentage of participants who had >=50% improvement (responders) in HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.

12. Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement in the HDRS17 Total Score at Week 6 (fITT Population) [Week 6]

    Percentage of participants who had >=50% improvement (responders) in HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.

13. Double-blind Treatment Period: Percentage of Participants With >= 30% Improvement on SIGH-A Total Score at Week 6 (eITT Population) [Week 6]

    The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had >= 30% improvement (responders) on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.

14. Double-blind Treatment Period: Percentage of Participants With >= 30% Improvement on SIGH-A Total Score at Week 6 (fITT Population) [Week 6]

    The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had >= 30% improvement (responders) on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.

15. Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement on SIGH-A Total Score at Week 6 (eITT Population) [Week 6]

    The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had >= 50% improvement (responders) on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.

16. Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement on SIGH-A Total Score at Week 6 (fITT Population) [Week 6]

    The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had >= 50% improvement (responders) on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.

17. Double-blind Treatment Period: Percentage of Participants With Remission as Assessed by HDRS17 Total Score Less Than or Equal to (<=) 7 at Week 6 (eITT Population) [Week 6]

    Percentage of participants with HDRS17 total score <= 7 were considered as remitters. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants with depression. Each of 17 items is rated by clinician on either 3-point(0-2) or 5-point(0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.

18. Double-blind Treatment Period: Percentage of Participants With Remission as Assessed by HDRS17 Total Score <= 7 at Week 6 (fITT Population) [Week 6]

    Percentage of participants with HDRS17 total score <= 7 were considered as remitters. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants with depression. Each of 17 items is rated by clinician on either 3-point(0-2) or 5-point(0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.

19. Double-blind Treatment Period: Percentage of Participants With a Clinical Global Impression Improvement (CGI-I) Score of Very Much Improved or Much Improved at Week 6 (eITT Population) [Week 6]

    The percentage of participants with a CGI-I score of very much improved or much improved at Week 6 was reported. CGI-I is a 7-point scale that required the clinician to assess how much the participant's illness had 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. For each individual item score and total score, higher scores indicate greater severity.

20. Double-blind Treatment Period: Percentage of Participants With a Clinical Global Impression Improvement (CGI-I) Score of Very Much Improved or Much Improved at Week 6 (fITT Population) [Week 6]

    The percentage of participants with a CGI-I score of very much improved or much improved at Week 6 was reported. CGI-I is a 7-point scale that required the clinician to assess how much the participant's illness had 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. For each individual item score and total score, higher scores indicate greater severity.

21. Maximum Plasma Concentration (Cmax) of JNJ-42165279 [Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77]

    Cmax is defined as maximum plasma concentration of JNJ-42165279. The data was pooled across visits at different timepoints to calculate Cmax.

22. Area Under the Plasma Concentration-time Curve From Zero to Dosing Intervals (AUC[0-tau]) of JNJ-42165279 [Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77]

    AUC(0-tau) is defined as area under the plasma concentration-time curve from 0 to t hours post dosing (time t is the dosing interval). The data was pooled across visits at different timepoints to calculate AUC(0-tau).

23. Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-42165279 [Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77]

    Tmax is defined as time to reach the maximum plasma concentration of JNJ-42165279. The data was pooled across visits at different timepoints to calculate Tmax.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participant must meet the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) or 5 diagnostic criteria for major depressive disorder (MDD) with Anxious Distress

• Participants with a diagnosis of comorbid Generalized Anxiety Disorder, Social Anxiety Disorder, or Panic Disorder may be included, if the investigator considers MDD with Anxious Distress to be the primary diagnosis (confirmed by an independent central rater at screening)

• Participants must have been treated with an approved SSRI/SNRI antidepressants for at least 6 continuous weeks, validated by an independent central rater contracted by the sponsor

• A 17-item Hamilton Depression Rating Scale (HDRS17) total score greater than or equal to (>=)18 and a HDRS17 anxiety/somatization factor score >=7 at screening, assessed by a site rater and reviewed by an independent central rater on Day 1

• Participant must be willing and able to adhere to the prohibitions and restrictions

• Participant Body mass index (BMI = weight/height2) must be between 18 and 35 kilogram per square meter (kg/m^2) inclusive

Exclusion Criteria:

• Has other psychiatric condition, including, but not limited to, MDD with psychotic features, bipolar disorder, obsessive-compulsive disorder, post-traumatic stress disorder, borderline personality disorder, eating disorder, or schizophrenia

• Has a length of current Major Depressive Episode (MDE) greater than (>) 6 months

• Has more than 1 failed antidepressant treatment of adequate dose and duration in the current MDE, Not including the inadequate response to the current selective serotonin reuptake inhibitor (SSRI) or serotonergic/noradrenergic reuptake inhibitor (SNRI) antidepressant

• Has initiated psychotherapy specific for MDD (such as cognitive behavioral, behavioral, or interpersonal therapy) for the current episode of depression within 6 weeks prior to Screening

• Has a current or recent history of clinically significant suicidal ideation within the past 6 months, or a history of suicidal behavior within the past year

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Costa Mesa	California	United States
2		Oceanside	California	United States
3		Miami	Florida	United States
4		Natick	Massachusetts	United States
5		Cedarhurst	New York	United States
6		Raleigh	North Carolina	United States
7		Allentown	Pennsylvania	United States
8		Salt Lake City	Utah	United States
9		Chisinau		Moldova, Republic of
10		Ekaterinburg		Russian Federation
11		Orenburg		Russian Federation
12		Saratov		Russian Federation
13		St-Petersburg		Russian Federation
14		Tomsk		Russian Federation
15		Alicante		Spain
16		Barcelona		Spain
17		Bilbao		Spain
18		Sant Boi de Llobregat		Spain
19		Zamora		Spain
20		Glevakha		Ukraine
21		Kharkiv		Ukraine
22		Kherson		Ukraine
23		Kyiv		Ukraine
24		Lviv		Ukraine
25		Smila		Ukraine
26		Uzhgorod		Ukraine
27		Barnsley		United Kingdom
28		Blackpool		United Kingdom
29		Liverpool		United Kingdom
30		Manchester		United Kingdom
31		South Staffordshire		United Kingdom
32		Stourton		United Kingdom

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 - Oct 24, 2017
• Statistical Analysis Plan - Feb 14, 2019

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02498392
• Other Study ID Numbers: CR107733; 2015-002007-29; 42165279MDD2001
• First Posted: Jul 15, 2015
• Last Update Posted: Apr 7, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Major Depressive Disorder; Depression; Anxiety symptoms; JNJ-42165279
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; JNJ-42165279

Study Results

Participant Flow

Pre-assignment Detail	Of the 161 enrolled participants, 1 participant withdrew from study participation prior to dosing. This participant has not been included in the analysis.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Period Title: Double-blind(DB) Lead-in Period(3 Weeks)
STARTED	160	0
Treated	153	0
COMPLETED	153	0
NOT COMPLETED	7	0
Period Title: Double-blind(DB) Lead-in Period(3 Weeks)
STARTED	76	77
COMPLETED	70	67
NOT COMPLETED	6	10

Baseline Characteristics

Arm/Group Title	Placebo	JNJ-42165279 25 mg	Total
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Total of all reporting groups
Overall Participants	76	77	153
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.4 (11.92)	42.1 (11.96)	43.2 (11.96)
Sex: Female, Male (Count of Participants)
Female	59 77.6%	53 68.8%	112 73.2%
Male	17 22.4%	24 31.2%	41 26.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 9.2%	6 7.8%	13 8.5%
Not Hispanic or Latino	67 88.2%	71 92.2%	138 90.2%
Unknown or Not Reported	2 2.6%	0 0%	2 1.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.3%	0 0%	1 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	3 3.9%	3 2%
White	73 96.1%	72 93.5%	145 94.8%
More than one race	1 1.3%	0 0%	1 0.7%
Unknown or Not Reported	1 1.3%	2 2.6%	3 2%
Region of Enrollment (Count of Participants)
MOLDOVA, REPUBLIC OF	8 10.5%	10 13%	18 11.8%
RUSSIAN FEDERATION	20 26.3%	21 27.3%	41 26.8%
SPAIN	3 3.9%	3 3.9%	6 3.9%
UKRAINE	18 23.7%	18 23.4%	36 23.5%
UNITED KINGDOM	18 23.7%	17 22.1%	35 22.9%
UNITED STATES	9 11.8%	8 10.4%	17 11.1%

Outcome Measures

1. Primary Outcome

Title	Double-blind Treatment Period: Change From Baseline in Hamilton Depression Rating Scale (HDRS17) Total Score at Week 6 (eITT Population)
Description	HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

The enriched intent-to-treat (eITT) analysis set included all enrolled participants who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Mean (Standard Deviation) [Units on a scale]	-6.1 (5.90)	-6.5 (4.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JNJ-42165279 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.416
	Comments
	Method	Mixed-effects Model for Repeated Measure
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square (LS) Means
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 60%; -1.10 to 0.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.04
	Estimation Comments

2. Primary Outcome

Title	Double-blind Treatment Period: Change From Baseline in HDRS17 Total Score at Week 6 (fITT Population)
Description	HDRS17 is a clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of the 17 items is rated by clinician on either a 3-point (0 to 2) or a 5-point (0 to 4) scale which used a rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. HDRS17 total score is calculated as sum of 17 item scores and ranges from 0 to 52. For each item as well as the total score, higher scores indicate greater severity of depression.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

The full intent-to-treat (fITT) analysis set included both placebo responders and placebo non-responders and defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and had at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Mean (Standard Deviation) [Units on a scale]	-5.0 (6.34)	-5.2 (4.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JNJ-42165279 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.647
	Comments	1-sided
	Method	Mixed-effects Model for Repeated Measure
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square (LS) Means
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 60%; -0.41 to 1.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.88
	Estimation Comments

3. Secondary Outcome

Title	Double-blind Treatment Period: Change From Baseline in Hamilton Anxiety Rating Subscale (HAM-A6) Score at Week 6 (eITT Population)
Description	The HAM-A6 is a 6-item subscale derived from the original Hamilton Anxiety scale (HAM-A) which consists of 5 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 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Mean (Standard Deviation) [Units on a scale]	-2.4 (3.15)	-2.9 (2.47)

4. Secondary Outcome

Title	Double-blind Treatment Period: Change From Baseline in HAM-A6 Score at Week 6 (fITT Population)
Description	The HAM-A6 is a 6-item subscale derived from the original Hamilton Anxiety scale (HAM-A) which consists of 5 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 6

Outcome Measure Data

Analysis Population Description

The Full ITT (fITT) Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Mean (Standard Deviation) [Units on a scale]	-2.1 (3.12)	-2.2 (2.68)

5. Secondary Outcome

Title	Double-blind Treatment Period: Change From Baseline in Hamilton Depression Rating Subscale (HAM-D6) Score at Week 6 (eITT Population)
Description	HAM-D6 is a 6-item subscale derived from HDRS17 and consists of depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and somatics symptoms (tiredness and pain), rated on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. 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 somatic is scored 0 to 2 and all others are scored 0 to 4. The HAM-D6 is calculated from summing the 6 items and the score ranges from 0 (normal) to 22 (severe), with higher scores indicating greater severity of core symptoms.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Mean (Standard Deviation) [Units on a scale]	-3.1 (3.20)	-3.6 (2.41)

6. Secondary Outcome

Title	Double-blind Treatment Period: Change From Baseline in HAM-D6 Score at Week 6 (fITT Population)
Description	HAM-D6 is a 6-item subscale derived from HDRS17 and consists of depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and somatic symptoms (tiredness and pain), rated on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. 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 somatic is scored 0 to 2 and all others are scored 0 to 4. The HAM-D6 is calculated from summing the 6 items and the score ranges from 0 (normal) to 22 (severe), with higher scores indicating greater severity of core symptoms.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Mean (Standard Deviation) [Unit on a Scale]	-2.6 (3.30)	-2.8 (2.78)

7. Secondary Outcome

Title	Double-blind Treatment Period: Change From Baseline in Structured Interview Guide of the Hamilton Anxiety Scale (SIGH-A) Total Score at Week 6 (eITT Population)
Description	The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety; 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, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Mean (Standard Deviation) [Units on a scale]	-5.7 (7.11)	-6.8 (5.62)

8. Secondary Outcome

Title	Double-blind Treatment Period: Change From Baseline in SIGH-A Total Score at Week 6 (fITT Population
Description	The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety; 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, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Mean (Standard Deviation) [Units on a Scale]	-5.0 (6.95)	-5.6 (5.86)

9. Secondary Outcome

Title	Double-blind Treatment Period: Change From Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (eITT Population)
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: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Each of 6 items is rated by clinician on either a 3-point (0 to 2) or a 5-point (0 to 4) scale with rating of 0:absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe and is calculated as sum of 6 item scores ranging from 0 to 18, with higher scores indicating greater severity of symptoms for each item as well as total score.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Mean (Standard Deviation) [Units on a scale]	-2.1 (2.35)	-2.3 (1.55)

10. Secondary Outcome

Title	Double-blind Treatment Period: Change From Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (fITT Population)
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: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Each of 6 items is rated by clinician on either a 3-point (0 to 2) or a 5-point (0 to 4) scale with rating of 0:absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe and is calculated as sum of 6 item scores ranging from 0 to 18, with higher scores indicating greater severity of symptoms for each item as well as total score.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Mean (Standard Deviation) [Unit on a Scale]	-1.7 (2.36)	-1.8 (1.69)

11. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With Greater Than or Equal to (>=) 30 Percent (%) Improvement on the HDRS17 Total Score at Week 6 (eITT Population)
Description	Percentage of participants who had >=30% improvement (responders) on HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Number [Percentage of participants]	51.1 67.2%	55.3 71.8%

12. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With >= 30 % Improvement on the HDRS17 Total Score at Week 6 (fITT Population)
Description	Percentage of participants who had >=30% improvement (responders) on HDRS17 total score at Week 6 was reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Number [Percentage of participants]	56.9 74.9%	52.2 67.8%

13. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement in the HDRS17 Total Score at Week 6 (eITT Population)
Description	Percentage of participants who had >=50% improvement (responders) in HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in DB treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Number [Percentage of participants]	27.7 36.4%	21.3 27.7%

14. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement in the HDRS17 Total Score at Week 6 (fITT Population)
Description	Percentage of participants who had >=50% improvement (responders) in HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Number [Percentage of participants]	36.1 47.5%	27.5 35.7%

15. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With >= 30% Improvement on SIGH-A Total Score at Week 6 (eITT Population)
Description	The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had >= 30% improvement (responders) on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Number [Percentage of participants]	48.9 64.3%	51.1 66.4%

16. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With >= 30% Improvement on SIGH-A Total Score at Week 6 (fITT Population)
Description	The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had >= 30% improvement (responders) on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Number [Percentage of participants]	52.8 69.5%	52.2 67.8%

17. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement on SIGH-A Total Score at Week 6 (eITT Population)
Description	The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had >= 50% improvement (responders) on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Number [Percentage of participants]	29.8 39.2%	21.3 27.7%

18. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement on SIGH-A Total Score at Week 6 (fITT Population)
Description	The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had >= 50% improvement (responders) on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Number [Percentage of participants]	37.5 49.3%	24.6 31.9%

19. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With Remission as Assessed by HDRS17 Total Score Less Than or Equal to (<=) 7 at Week 6 (eITT Population)
Description	Percentage of participants with HDRS17 total score <= 7 were considered as remitters. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants with depression. Each of 17 items is rated by clinician on either 3-point(0-2) or 5-point(0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double-blind treatment period, who were lead-in placebo non-responder,who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Number [Percentage of participants]	14.9 19.6%	8.5 11%

20. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With Remission as Assessed by HDRS17 Total Score <= 7 at Week 6 (fITT Population)
Description	Percentage of participants with HDRS17 total score <= 7 were considered as remitters. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants with depression. Each of 17 items is rated by clinician on either 3-point(0-2) or 5-point(0-4) scale with 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 scores of all 17 items. For each item as well as total score, higher score represents more severe condition.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Number [Percentage of participants]	33.3 43.8%	21.7 28.2%

21. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With a Clinical Global Impression Improvement (CGI-I) Score of Very Much Improved or Much Improved at Week 6 (eITT Population)
Description	The percentage of participants with a CGI-I score of very much improved or much improved at Week 6 was reported. CGI-I is a 7-point scale that required the clinician to assess how much the participant's illness had 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. For each individual item score and total score, higher scores indicate greater severity.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The eITT analysis set included all enrolled participants who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	47	47
Number [Percentage of participants]	57.4 75.5%	55.3 71.8%

22. Secondary Outcome

Title	Double-blind Treatment Period: Percentage of Participants With a Clinical Global Impression Improvement (CGI-I) Score of Very Much Improved or Much Improved at Week 6 (fITT Population)
Description	The percentage of participants with a CGI-I score of very much improved or much improved at Week 6 was reported. CGI-I is a 7-point scale that required the clinician to assess how much the participant's illness had 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. For each individual item score and total score, higher scores indicate greater severity.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Arm/Group Title	Placebo	JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	72	69
Number [Percentage of participate]	65.3	65.2

23. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of JNJ-42165279
Description	Cmax is defined as maximum plasma concentration of JNJ-42165279. The data was pooled across visits at different timepoints to calculate Cmax.
Time Frame	Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic analysis set included all participants who received at least 1 dose of JNJ-42165279 and with measurable JNJ-42165279 concentrations in plasma. Here "n (number analyzed)" is defined as number of participants analyzed for specified categories.

Arm/Group Title	JNJ-42165279 25 mg
Arm/Group Description	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	77
Male	217.7
Female	229.3

24. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Zero to Dosing Intervals (AUC[0-tau]) of JNJ-42165279
Description	AUC(0-tau) is defined as area under the plasma concentration-time curve from 0 to t hours post dosing (time t is the dosing interval). The data was pooled across visits at different timepoints to calculate AUC(0-tau).
Time Frame	Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic analysis set included all participants who received at least 1 dose of JNJ-42165279 and with measurable JNJ-42165279 concentrations in plasma. Here "n (number analyzed)" is defined as number of participants analyzed for specified category.

Arm/Group Title	JNJ-42165279 25 mg
Arm/Group Description	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	77
Male	2159
Female	2432

25. Secondary Outcome

Title	Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-42165279
Description	Tmax is defined as time to reach the maximum plasma concentration of JNJ-42165279. The data was pooled across visits at different timepoints to calculate Tmax.
Time Frame	Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic analysis set included all participants who received at least 1 dose of JNJ-42165279 and with measurable JNJ-42165279 concentrations in plasma. Sparse samples was collected between 2 hours and 4 hours. It was not possible to accurately determine Tmax as Cmax is expected to be around 1 hour post-dose.

Arm/Group Title	JNJ-42165279 25 mg
Arm/Group Description	Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
Measure Participants	77
Median (Full Range) [Hours]	NA

Adverse Events

Time Frame	Up to Week 18
Adverse Event Reporting Description	Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title	Double-blind (DB) Lead-in Period: Placebo		DB Treatment + Withdrawal Period: Placebo		DB Treatment + Withdrawal Period: JNJ-42165279 25 mg
Arm/Group Description	All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period.		All participants received matching placebo tablets orally qd during the double blind lead-in period. Participants were then assessed for response according to criteria based on reduction from lead-in baseline in Hamilton depression rating scale (HDRS17) and continued to receive adjunctive matching placebo tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.		Participants receiving matching placebo tablets during the double blind lead-in period were randomized to receive JNJ-42165279 25 milligrams (mg) tablets orally qd for 6 weeks during the double-blind treatment period. Participants who completed the double-blind treatment period prior to Week 11 entered the withdrawal period and were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific participant.
All Cause Mortality
	Double-blind (DB) Lead-in Period: Placebo		DB Treatment + Withdrawal Period: Placebo		DB Treatment + Withdrawal Period: JNJ-42165279 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/160 (0%)		0/76 (0%)		0/77 (0%)
Serious Adverse Events
	Double-blind (DB) Lead-in Period: Placebo		DB Treatment + Withdrawal Period: Placebo		DB Treatment + Withdrawal Period: JNJ-42165279 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/160 (1.3%)		1/76 (1.3%)		1/77 (1.3%)
Infections and infestations
Gastroenteritis	1/160 (0.6%)		1/76 (1.3%)		0/77 (0%)
Musculoskeletal and connective tissue disorders
Foot Deformity	1/160 (0.6%)		0/76 (0%)		1/77 (1.3%)
Other (Not Including Serious) Adverse Events
	Double-blind (DB) Lead-in Period: Placebo		DB Treatment + Withdrawal Period: Placebo		DB Treatment + Withdrawal Period: JNJ-42165279 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/160 (10%)		4/76 (5.3%)		3/77 (3.9%)
Nervous system disorders
Headache	16/160 (10%)		4/76 (5.3%)		3/77 (3.9%)

Limitations/Caveats

The relationship of plasma anandamide and trough drug concentrations observed suggest that few participants had substantial recovery of fatty acid amide hydrolase activity between doses. Higher doses or exposures could have resulted in greater effects.

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. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.