A Study of JNJ-55308942 in the Treatment of Bipolar Depression

Change From Baseline in MADRS Total Score up to Week 6 (Diagnosis Subgroup Analysis)

Change from baseline in MADRS total score up to Week 6 (Diagnosis Subgroup Analysis) were reported. Diagnosis subgroup analysis included participants with bipolar type 1 or II. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

Time frame: From Baseline (Day 1) up to Week 6

Change From Baseline in MADRS Total Score up to Week 6 (Biomarker Subgroup Analysis)

Biomarker subgroup analysis included specific (3-Marker Model \[3MM\]) biomarker profile: Yes or No. 3MM biomarker profile was defined as serum C-reactive protein \>3 mg/Liter(L) and soluble interleukin-6 receptor \>25 micrograms(mcg)/L or tumor necrosis factor \>4 nanograms(ng)/L at baseline. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Scale consist of 10 items each of which was scored from 0(item not present or normal) to 6(severe or continuous presence of the symptoms),with higher score indicating a more severe condition. MADRS total score was sum of scores from individual question items, ranged from 0 to 60,with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

Time frame: From Baseline (Day 1) up to Week 6

Number of Participants With Treatment-emergent Clinically Important Abnormalities in Vital Signs

Vital signs parameters included pulse rate (abnormally low \[AL\]: \<50 beats per minute \[bpm\] and with \>15 bpm decrease from baseline and abnormally high \[AH\]: \>100 bpm and with \>15 bpm increase from baseline), Systolic blood pressure (SBP) (AL: \<90 millimeters of mercury \[mmHg\] and with \>20 mmHg decrease from baseline and AH: \>180 mmHg and with \>20 mmHg increase from baseline), Diastolic blood pressure (DBP) (AL: \<50 mmHg and with \>15 mmHg decrease from baseline and AH: \>105 mmHg and with \>15 mmHg increase from baseline) , temperature (AL:\<35.5 and AH:\>37.5 degree Celsius \[C\]), respiratory rate (AH :\>20 breaths per minute), and weight (AL: decrease from baseline \>7% and AH: increase from baseline \>7%). Weight was planned to analyzed at Weeks 6 and 8 only. Treatment-emergent concluded if postbaseline value was above/below upper/lower limit and baseline value was below/above the upper/lower limit.

Time frame: Weeks 1, 2, 4, 6, and 8 (Follow-up/Early Withdrawal)

Change From Baseline in Clinical Laboratory Values in Male Hormone: Inhibin B

Change from baseline in clinical laboratory values in male hormone (Inhibin B) were reported.

Time frame: Baseline (Day 1), Week 4, 6, and 8 (Follow-up/Early Withdrawal)

Change From Baseline in Clinical Laboratory Values in Male Hormone: Luteinizing Hormone

Change from baseline in clinical laboratory values in male hormone (luteinizing hormone) were reported.

Time frame: Baseline (Day 1), Week 4, 6, and 8 (Follow-up/Early Withdrawal)

Change From Baseline in Clinical Laboratory Values in Male Hormone: Prolactin

Change from baseline in clinical laboratory values in male hormone (prolactin) were reported.

Time frame: Baseline (Day 1), Week 4, 6, and 8 (Follow-up/Early Withdrawal)

Change From Baseline in Clinical Laboratory Values in Male Hormones: Sex Hormone Binding Globulin, Testosterone (Free), Testosterone (High Sensitivity), and Testosterone (Low Sensitivity)

Change from baseline in clinical laboratory values in male hormones (sex hormone binding globulin, testosterone \[free\], testosterone \[high sensitivity\], and testosterone \[low sensitivity\]) were reported.

Time frame: Baseline (Day 1), Week 4, 6, and 8 (Follow-up/Early Withdrawal)

Number of Participants With Abnormal Laboratory Values: Serum Chemistry

Number of participants with abnormal laboratory values: serum chemistry were reported. It included: aspartate aminotransferase (high), alanine aminotransferase (high), bilirubin (high/low), and alkaline phosphatase (high/low). Only categories with data were reported.

Time frame: Weeks 2, 4, 6, and 8 (Follow-up/Early Withdrawal)

Number of Participants With Clinically Significant Abnormal Laboratory Values: Hematology

Number of participants with clinically significant abnormal laboratory values: hematology were reported.

Time frame: Weeks 2, 4, 6, and 8 (Follow-up/Early Withdrawal)

Number of Participants With Clinically Significant Abnormal Laboratory Values: Urinalysis

Number of participants with clinically significant abnormal laboratory values: urinalysis were reported.

Time frame: Weeks 2, 4, 6, and 8 (Follow-up/Early Withdrawal)

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Number of participants with TEAEs were reported. An adverse event (AE) is any untoward medical occurrence in a clinical study participants who administered a medicinal (investigational or non-investigational) product and does not necessarily have a causal relationship with the treatment. A TEAE defined as an AE that occurred at or after the first dose administration up to day of the last dose plus 30 days.

Time frame: Day 1 (Week 0) up to 30 days after the last dose (up to 11 weeks)

Number of Participants With Treatment-emergent Abnormalities in Electrocardiograms (ECGs)

Number of participants with treatment-emergent abnormalities in ECGs were reported. It included ECG mean heart rate (abnormally low \[AL\]: \<50 and abnormally high \[AH\]: \>100 beats per minute \[bpm\]), PR Interval (AL: \<120 and AH: \>200 milliseconds \[msec\]), QRS Duration (AL: \<60 and AH: \>120 msec), and QT Interval (AL: \<200 and AH: \>500 msec). A treatment-emergent abnormalities in ECGs are defined as those abnormalities that occurred at or after the first dose administration.

Time frame: Weeks 1, 2, 4, 6, and 8 (Follow-up/Early Withdrawal)

Change From Baseline in Young Mania Rating Scale (YMRS) Total Score

Change from baseline in YMRS total score were reported. The YMRS was designed to measure the severity of manic symptoms, to gauge the effect of treatment on mania severity, and to detect a return of manic symptoms (for example relapse or recurrence). YMRS had 11 items : 4 items (irritability, speech, thought content, and disruptive/aggressive behavior) were graded on a scale of 0 to 8 and the remaining 7 items (elevated mood, increased motor activity, sexual interest, sleep, language-thought disorder, appearance, and insight) were graded on a scale of 0 to 4. Higher scores indicated greater symptom severity. Responses were summed to yield YMRS total score ranged from 0 to 60 , with higher scores reflecting greater severity of mania.

Time frame: From Baseline (Day 1) up to Week 6

Number of Participants Who Reported Suicidal Ideation (SI) or Suicidal Behavior (SB) Using With Columbia Suicide Severity Rating Scale (C-SSRS) Score

C-SSRS is a clinician-rated instrument that reports severity of both suicidal ideation (SI) and suicidal behavior (SB). SI categories: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods \[not plan\] without intent to act), 4 (active SI with some intent to act, without specific plan), and 5 (active SI with specific plan and intent). SB categories: 6 (preparatory acts or behavior), 7 (aborted attempt), 8 (interrupted attempt), 9 (actual attempt), and 10 (suicide). An additional category for non-suicide: non-suicidal self-injurious behavior. SI/SB was indicated by a "yes" answer to any of the listed categories. Score of 0 (no SI or SB) was assigned. Maximum score of 1 to 10 was assigned if suicidal ideation or behavior was present. Scoring was grouped into 3 categories: No SI/SB (0), SI (score 1 to 5), and SB (score 6 to 10), with higher scores indicating more severe ideation/behavior.

Time frame: From Baseline (Day 1) up to Week 8

Change From Baseline in Clinical Global Impression-Severity Scale (CGI-S) Score

Change from baseline in CGI-S score were reported. The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of mental illness exhibited by a participant, and rated on a scale of 1 to 7: 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Higher scores indicate worsening. Negative change in CGI-S score indicate improvement.

Time frame: From Baseline (Day 1) up to Week 6

Plasma Concentrations of JNJ-55308942

Plasma concentrations of JNJ-55308942 were reported.

Time frame: Predose, 1.5 hours and 4 hours post-dose on Week 0 (Day 1), Weeks 1 (Day 8), 2 (Day 15), 4 (Day 29), and 6 (Day 43)

Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Score - Ability to Participate in Social Roles and Activities (APS) T-Scores

Change from baseline in PROMIS score - ability to participate in social roles and activities T-Scores were reported. The PROMIS - APS item bank assessed the perceived ability to perform one's usual social roles and activities. The item bank did not use a time frame (for example, over the past seven days) when assessing the APS. The Short Form 4a included 4 items that represent this concept. Each question had 5 response options ranging in value from 1 to 5 with higher scores indicating better social function. The total raw score for the short form was calculated by summing the values of the response to each question, so for the 4-item form, the lowest possible raw score was 4; the highest possible raw score was 20. The total raw score was converted to a T score with a mean of 50 and a standard deviation of 10. Higher T-scores indicate better social function.

Time frame: Baseline (Day 1), Weeks 1, 2, 3, 4, 5, and 6

Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score

Change from baseline in PHQ-9 total score were reported. PHQ-9 is 9-item, self-report scale assessed depressive symptoms. Each item was rated on 4-point scale (0=Not at all, 1=several days, 2=more than half days, 3=nearly every day. The participant's item responses were summed to provide PHQ-9 total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms.

Time frame: Baseline (Day 1), Weeks 1, 2, 3, 4, 5, and 6

Change From Baseline in Generalized Anxiety Disorder 7 (GAD-7) Total Score

Change from baseline in GAD-7 total score were reported. GAD-7 is a brief and validated 7-item self-reported questionnaire for assessment of overall GAD. Participants responded to each item using a 4-point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day, with a higher score representing a more severe condition. Item responses were summed to yield GAD-7 total score which ranged of 0 to 21, where higher scores indicated more anxiety.

Time frame: Baseline (Day 1), Weeks 2, 4, and 6

Number of Participants Who Achieved Response at Week 6

Number of participants who achieved response at Week 6 were reported. Response was defined as greater than or equal to (\>=)50% improvement in MADRS total score from baseline. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

Time frame: Week 6

Number of Participants Who Achieved Remission at Week 6

Number of participants who achieved remission at Week 6 were reported. Remission was defined as MADRS total score \<=12. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

Time frame: Week 6

Change From Baseline in MADRS Total Score up to Week 6 (Subgroup of Participants With Messenger Ribonucleic Acid [mRNA] Transcript Levels)

Change from baseline in MADRS total score up to Week 6 (subgroup of participants with mRNA transcript levels) was planned to be reported. Subgroup included participants with mRNA transcript levels at baseline that exceeded the medium level for both P2RX7 and IL-1-beta. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

Time frame: From Baseline (Day 1) up to Week 6

Change From Baseline in MADRS Total Score up to Week 6 (Concomitant Medication Subgroup Analysis)

Change from baseline in MADRS total score up to Week 6 (concomitant medication subgroup analysis) was reported. Concomitant medication subgroup analysis included subjects with BD not taking any mood stabilizer or antipsychotic, taking a mood stabilizer alone, taking antipsychotic alone, and taking a combination of mood stabilizer and an antipsychotic. MADRS measures depression severity, detects changes due to AD treatment. It consists of 10 items (evaluate apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed to total possible score of 0 to 60. Higher scores indicate more severe conditions. Negative change in score indicates improvement.

Time frame: From Baseline (Day 1) up to Week 6