Trial Outcomes & Findings for An Efficacy, Safety and Tolerability Study of JNJ-42165279 in Participants With Major Depressive Disorder With Anxious Distress (NCT NCT02498392)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

161 participants

Primary outcome timeframe

Baseline and Week 6

Results posted on

2025-04-29

Participant Flow

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

Participant milestones

Participant milestones
Measure	Placebo 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.	JNJ-42165279 25 mg 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.
Double-blind(DB) Lead-in Period(3 Weeks) STARTED	160	0
Double-blind(DB) Lead-in Period(3 Weeks) Treated	153	0
Double-blind(DB) Lead-in Period(3 Weeks) COMPLETED	153	0
Double-blind(DB) Lead-in Period(3 Weeks) NOT COMPLETED	7	0
DB Treatment (6 Weeks)+Withdrawal Period STARTED	76	77
DB Treatment (6 Weeks)+Withdrawal Period COMPLETED	70	67
DB Treatment (6 Weeks)+Withdrawal Period NOT COMPLETED	6	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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.	JNJ-42165279 25 mg 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.
Double-blind(DB) Lead-in Period(3 Weeks) Did not receive treatment	7	0
DB Treatment (6 Weeks)+Withdrawal Period Adverse Event	3	0
DB Treatment (6 Weeks)+Withdrawal Period Lack of Efficacy	0	2
DB Treatment (6 Weeks)+Withdrawal Period Lost to Follow-up	0	2
DB Treatment (6 Weeks)+Withdrawal Period Withdrawal by Subject	2	3
DB Treatment (6 Weeks)+Withdrawal Period Other	1	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=76 Participants 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.	JNJ-42165279 25 mg n=77 Participants 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 n=153 Participants Total of all reporting groups
Age, Continuous	44.4 years STANDARD_DEVIATION 11.92 • n=5 Participants	42.1 years STANDARD_DEVIATION 11.96 • n=7 Participants	43.2 years STANDARD_DEVIATION 11.96 • n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	53 Participants n=7 Participants	112 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	24 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=5 Participants	71 Participants n=7 Participants	138 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	73 Participants n=5 Participants	72 Participants n=7 Participants	145 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment MOLDOVA, REPUBLIC OF	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment RUSSIAN FEDERATION	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Region of Enrollment SPAIN	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment UKRAINE	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment UNITED KINGDOM	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment UNITED STATES	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
Double-blind Treatment Period: Change From Baseline in Hamilton Depression Rating Scale (HDRS17) Total Score at Week 6 (eITT Population)	-6.1 Units on a scale Standard Deviation 5.90 • Interval 5.9 to	-6.5 Units on a scale Standard Deviation 4.01 • Interval 4.01 to

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Change From Baseline in HDRS17 Total Score at Week 6 (fITT Population)	-5.0 Units on a scale Standard Deviation 6.34 • Interval 6.34 to	-5.2 Units on a scale Standard Deviation 4.68 • Interval 4.68 to

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
Double-blind Treatment Period: Change From Baseline in Hamilton Anxiety Rating Subscale (HAM-A6) Score at Week 6 (eITT Population)	-2.4 Units on a scale Standard Deviation 3.15 • Interval 3.15 to	-2.9 Units on a scale Standard Deviation 2.47 • Interval 2.47 to

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Change From Baseline in HAM-A6 Score at Week 6 (fITT Population)	-2.1 Units on a scale Standard Deviation 3.12	-2.2 Units on a scale Standard Deviation 2.68

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
Double-blind Treatment Period: Change From Baseline in Hamilton Depression Rating Subscale (HAM-D6) Score at Week 6 (eITT Population)	-3.1 Units on a scale Standard Deviation 3.20 • Interval 3.2 to	-3.6 Units on a scale Standard Deviation 2.41 • Interval 2.41 to

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Change From Baseline in HAM-D6 Score at Week 6 (fITT Population)	-2.6 Unit on a Scale Standard Deviation 3.30	-2.8 Unit on a Scale Standard Deviation 2.78

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
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)	-5.7 Units on a scale Standard Deviation 7.11 • Interval 7.11 to	-6.8 Units on a scale Standard Deviation 5.62 • Interval 5.62 to

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Change From Baseline in SIGH-A Total Score at Week 6 (fITT Population	-5.0 Units on a Scale Standard Deviation 6.95	-5.6 Units on a Scale Standard Deviation 5.86

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
Double-blind Treatment Period: Change From Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (eITT Population)	-2.1 Units on a scale Standard Deviation 2.35 • Interval 2.35 to	-2.3 Units on a scale Standard Deviation 1.55 • Interval 1.55 to

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Change From Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (fITT Population)	-1.7 Unit on a Scale Standard Deviation 2.36	-1.8 Unit on a Scale Standard Deviation 1.69

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
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)	51.1 Percentage of participants	55.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Percentage of Participants With >= 30 % Improvement on the HDRS17 Total Score at Week 6 (fITT Population)	56.9 Percentage of participants	52.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement in the HDRS17 Total Score at Week 6 (eITT Population)	27.7 Percentage of participants	21.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement in the HDRS17 Total Score at Week 6 (fITT Population)	36.1 Percentage of participants	27.5 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
Double-blind Treatment Period: Percentage of Participants With >= 30% Improvement on SIGH-A Total Score at Week 6 (eITT Population)	48.9 Percentage of participants	51.1 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Percentage of Participants With >= 30% Improvement on SIGH-A Total Score at Week 6 (fITT Population)	52.8 Percentage of participants	52.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement on SIGH-A Total Score at Week 6 (eITT Population)	29.8 Percentage of participants	21.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement on SIGH-A Total Score at Week 6 (fITT Population)	37.5 Percentage of participants	24.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
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)	14.9 Percentage of participants	8.5 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
Double-blind Treatment Period: Percentage of Participants With Remission as Assessed by HDRS17 Total Score <= 7 at Week 6 (fITT Population)	33.3 Percentage of participants	21.7 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants 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.	JNJ-42165279 25 mg n=47 Participants 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.
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)	57.4 Percentage of participants	55.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants 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.	JNJ-42165279 25 mg n=69 Participants 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.
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)	65.3 Percentage of participate	65.2 Percentage of participate

SECONDARY outcome

Timeframe: Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77

Population: 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.

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

Outcome measures

Outcome measures
Measure	Placebo n=77 Participants 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.	JNJ-42165279 25 mg 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.
Maximum Plasma Concentration (Cmax) of JNJ-42165279 Male	217.7 Nanograms/milliliter (ng/mL) Interval 178.4 to 281.7	—
Maximum Plasma Concentration (Cmax) of JNJ-42165279 Female	229.3 Nanograms/milliliter (ng/mL) Interval 142.9 to 337.7	—

SECONDARY outcome

Timeframe: Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo n=77 Participants 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.	JNJ-42165279 25 mg 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.
Area Under the Plasma Concentration-time Curve From Zero to Dosing Intervals (AUC[0-tau]) of JNJ-42165279 Male	2159 Nanogramshour/milliliter (ngh/mL) Interval 1353.0 to 3385.0	—
Area Under the Plasma Concentration-time Curve From Zero to Dosing Intervals (AUC[0-tau]) of JNJ-42165279 Female	2432 Nanogramshour/milliliter (ngh/mL) Interval 1137.0 to 4288.0	—

SECONDARY outcome

Timeframe: Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=77 Participants 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.	JNJ-42165279 25 mg 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.
Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-42165279	NA Hours With the sparse sampling collected between 2 and 4 hours it was not possible to accurately determine Tmax as Cmax is expected to be around 1h post-dose.	—

Adverse Events

Double-blind (DB) Lead-in Period: Placebo

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

DB Treatment + Withdrawal Period: Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

DB Treatment + Withdrawal Period: JNJ-42165279 25 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-blind (DB) Lead-in Period: Placebo n=160 participants at risk All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period.	DB Treatment + Withdrawal Period: Placebo n=76 participants at risk 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.	DB Treatment + Withdrawal Period: JNJ-42165279 25 mg n=77 participants at risk 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.
Infections and infestations Gastroenteritis	0.62% 1/160 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	1.3% 1/76 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/77 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Foot Deformity	0.62% 1/160 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	0.00% 0/76 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	1.3% 1/77 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	Double-blind (DB) Lead-in Period: Placebo n=160 participants at risk All participants received matching placebo tablets orally once daily (qd) during the double blind lead-in period.	DB Treatment + Withdrawal Period: Placebo n=76 participants at risk 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.	DB Treatment + Withdrawal Period: JNJ-42165279 25 mg n=77 participants at risk 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.
Nervous system disorders Headache	10.0% 16/160 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	5.3% 4/76 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.	3.9% 3/77 • Up to Week 18 Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Additional Information

Senior Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER