Major Depressive Disorder With Anxious Distress
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy of JNJ-61393215 as adjunctive treatment compared to adjunctive placebo, as assessed by the change from baseline to week 6 on a 17-item Hamilton Depression Rating Scale (HDRS-17) in participants with major depressive disorder (MDD) with anxious distress with a score greater than or equal to (\>=) 2 on item 26 or 27 of the Inventory of Depressive Symptomatology, Clinician Rating -30 (IDS-C30), who have a suboptimal response to current treatment with a standard antidepressant.
Interventions
DRUGJNJ-61393215
JNJ-61393215 will be administrated orally.
DRUGPlacebo
Matching placebo will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have a body mass index (BMI) between 18 and 36 kilogram per meter square (kg/m\^2) * Participants must have a primary diagnostic and statistical manual of mental disorders, 5th edition (DSM-5) diagnosis of major depressive disorder (MDD) with anxious distress, as assessed by the mini international neuropsychiatric inventory 7.0. Plus (MINI). Participants with a diagnosis of comorbid generalized anxiety disorder (GAD), post-traumatic stress disorder, persistent depressive disorder, attention deficit hyperactivity disorder (ADHD), social anxiety disorder or nicotine/caffeine dependence may be included, if MDD is primary diagnosis * Participants must have an inventory of depressive symptomatology, clinician rating-30 (IDS-C30) total score greater than or equal to (\>=) 35 (moderate to severe depression) * Participant must not have received more than 3 failed antidepressant treatments (of adequate dose and duration), including their current treatment, in the current episode of depression, as documented by the massachusetts general hospital antidepressant treatment history questionnaire (MGH-ATRQ) * Participant must be currently receiving 1 of the following antidepressants for at least 6 weeks duration at screening, at an adequate therapeutic dose, as determined by the MGH-ATRQ and should remain on a stable dose throughout the study: bupropion, citalopram, escitalopram, sertraline, paroxetine, venlafaxine, desvenlafaxine, duloxetine, fluoxetine, vilazodone, vortioxetine, mirtazapine, agomelatine, nortriptyline, imipramine, amitriptyline and levomilnacipran * Participants must have a suboptimal response (improvement \<50%) to the antidepressant used as their current treatment, as measured by the MGH-ATRQ * A woman of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose
Exclusion criteria
* Participant has any other psychiatric condition including but not limited to: MDD with current psychotic features, bipolar disorder (including lifetime diagnosis), obsessive-compulsive disorder, borderline personality disorder, eating disorder (example: bulimia, anorexia nervosa), or schizophrenia (lifetime) * Age of onset of depression is after 55 years of age * Participant has a history of alcohol or substance use disorder (abuse/dependence) within 6 months prior to screening (nicotine and caffeine dependence are not exclusionary) * Participant has a current or recent (within the past year) history of clinically significant suicidal ideation (corresponding to a score of \>= 3 for ideation) or any suicidal behavior within the past year, as validated on the Colombia suicide severity rating scale (C-SSRS) at screening or baseline * Length of current major depressive episode \>60 months * Participant has organic brain disease or dementia or has known or suspected intellectual development disorder * Participant has been treated with at least one of the following treatments: (a) electroconvulsive therapy in the current episode; (b) deep brain stimulation (lifetime); (c) repetitive transcranial magnetic stimulation within 4 weeks prior to baseline visit * Participant has any clinically relevant medical condition that could potentially alter the absorption, metabolism, or excretion of the study intervention, such as liver disease or renal disease * Participant has a relevant history of any significant and/or unstable cardiovascular, respiratory, neurological (including seizures - uncomplicated childhood febrile seizures with no sequelae are not exclusionary) or significant cerebrovascular, renal, hepatic, dermatologic, hematologic, gastrointestinal or endocrine diseases. Hospitalization for cardiovascular event (myocardial infarction, unstable angina, stroke, transient ischemic attack) within 3 months prior to the first administration of study drug is exclusionary. Diabetes mellitus be allowed when the participant is stable (HbA1c less than 7.5% or 58 mmol/mol) * Participant has a clinically significant abnormal physical examination, vital signs or 12-lead electrocardiogram (ECG) at screening or baseline Minor deviations in ECG, which are not considered to be of clinical significance to the investigator, are acceptable.If at screening visit QTcB or QTcF interval \>=450 ms for males or \>=470 ms for females, or \>480 ms if bundle branch block and prolongation of the QTc interval are present;participant is excluded * Participant has a history of known demyelinating diseases such as multiple sclerosis or optic neuritis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hamilton Depression Rating Scale-17 (HDRS-17) Total Score at Week 6 | Baseline and Week 6 | Change from baseline in HDRS-17 total score at Week 6 was reported. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition (greater depression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HAM-A Total Score at Weeks 2 and 4 | Baseline, Week 2, and Week 4 | Change from baseline in HAM-A total score at Weeks 2 and 4 were reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13: normal range, 14-17: mild severity, 18-24: mild to moderate severity, 25-30: moderate to severe, and \>=31: severe. Negative change in score indicates improvement. |
| Change From Baseline in HDRS-17 Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6 | Baseline and Week 6 | Change from baseline in HDRS-17 total score in participants with a baseline HAM-A score \>=20 at Week 6 was reported. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition (greater depression). |
| Change From Baseline in HAM-A Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6 | Baseline and Week 6 | Change from baseline in HAM-A total score in participants with a baseline HAM-A score \>=20 at Week 6 was reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13: normal range, 14-17: mild severity, 18-24: mild to moderate severity, 25-30: moderate to severe, and \>=31: severe. Negative change in score indicates improvement. |
| Change From Baseline in Generalized Anxiety Disorder-7 (GAD-7) Total Score at Week 6 | Baseline and Week 6 | Change from baseline in GAD-7 total score at Week 6 was reported. The GAD-7 is a brief and validated 7-item self-reported assessment of overall anxiety. Participants respond 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. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15-21). |
| Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Week 6 | Baseline and Week 6 | Change from baseline in HAM-A total score at Week 6 was reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13: normal range, 14-17: mild severity, 18-24: mild to moderate severity, 25-30: moderate to severe, and \>=31: severe. Negative change in score indicates improvement. |
| Total Plasma Concentration of JNJ-61393215 | 1-4 hours postdose on Day 1; Predose and 1-4 hours post dose on Days 15, 29, and 43 | Total plasma concentration of JNJ-61393215 was reported. The concentrations of JNJ-61393215 were measured using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. |
| Change From Baseline in HDRS-17 Total Score at Weeks 2 and 4 | Baseline, Week 2, and Week 4 | Change From baseline in HDRS-17 total score at Weeks 2 and 4. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition (greater depression). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability | Up to 8 weeks | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events during the initiation of study drug up till follow-up period. |
| Plasma Protein Binding (PPB): Percentage of JNJ-61393215 Unbound | Predose and 1-4 hours post dose on Day 43 | Percentage of JNJ-61393215 unbound was determined by using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. The protein binding was assessed by spiking plasma samples with radiolabeled JNJ-61393215. |
| Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 2 and 4 | Baseline, Week 2, and Week 4 | Change From baseline in PHQ-9 total score at Weeks 2 and 4. The PHQ-9 is a 9-item, Patient Reported Outcome (PRO) measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participants item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19) and Severe (20-27). |
Countries
Moldova, Russia, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo After a screening period of up to 4 weeks duration, participants received placebo matching to JNJ-61393215 capsule orally once daily during 6 weeks double-blind treatment period, followed by 2 weeks post treatment follow-up period. Throughout the study, participants continued their standard treatment of oral antidepressants at an adequate and tolerated stable dose. | 112 |
| JNJ-61393215 135 Milligrams (mg) After a screening period of up to 4 weeks duration, participants received JNJ-61393215 135 mg (3\*45 mg) capsule orally once daily during 6 weeks double-blind treatment period, followed by 2 weeks post treatment follow-up period. Throughout the study, participants continued their standard treatment of oral antidepressants at an adequate and tolerated stable dose. | 110 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-Compliance with Study Drug | 0 | 1 |
| Overall Study | Other | 2 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | JNJ-61393215 135 Milligrams (mg) |
|---|---|---|---|
| Age, Continuous | 39.9 years STANDARD_DEVIATION 12.99 | 41.7 years STANDARD_DEVIATION 12.8 | 43.6 years STANDARD_DEVIATION 12.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 26 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 97 Participants | 192 Participants | 95 Participants |
| Region of Enrollment MOLDOVA, REPUBLIC OF | 18 Participants | 35 Participants | 17 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 36 Participants | 70 Participants | 34 Participants |
| Region of Enrollment UKRAINE | 22 Participants | 43 Participants | 21 Participants |
| Region of Enrollment UNITED KINGDOM | 10 Participants | 19 Participants | 9 Participants |
| Region of Enrollment UNITED STATES | 26 Participants | 55 Participants | 29 Participants |
| Sex: Female, Male Female | 79 Participants | 167 Participants | 88 Participants |
| Sex: Female, Male Male | 33 Participants | 55 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 112 | 0 / 110 |
| other Total, other adverse events | 12 / 112 | 30 / 110 |
| serious Total, serious adverse events | 0 / 112 | 0 / 110 |
Outcome results
Primary
Change From Baseline in Hamilton Depression Rating Scale-17 (HDRS-17) Total Score at Week 6
Change from baseline in HDRS-17 total score at Week 6 was reported. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition (greater depression).
Time frame: Baseline and Week 6
Population: The enriched analysis set (EAS) included all randomized participants who received at least 1 dose of study agent and had improvement in percent changes in HDRS17 total score less than (\<)25 percent (%) from screening to baseline and HDRS-17 total score greater than or equal to (\>=)18 at baseline. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hamilton Depression Rating Scale-17 (HDRS-17) Total Score at Week 6 | -8.8 Units on a scale | Standard Error 0.66 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in Hamilton Depression Rating Scale-17 (HDRS-17) Total Score at Week 6 | -9.4 Units on a scale | Standard Error 0.64 |
p-value: 0.249480% CI: [-1.76, 0.55]Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline in Generalized Anxiety Disorder-7 (GAD-7) Total Score at Week 6
Change from baseline in GAD-7 total score at Week 6 was reported. The GAD-7 is a brief and validated 7-item self-reported assessment of overall anxiety. Participants respond 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. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15-21).
Time frame: Baseline and Week 6
Population: The EAS included all randomized participants who received at least 1 dose of study agent and had improvement in percent changes in HDRS17 total score \<25% from screening to baseline and HDRS-17 total score \>=18 at baseline. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Generalized Anxiety Disorder-7 (GAD-7) Total Score at Week 6 | -5.3 Units on a scale | Standard Error 0.52 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in Generalized Anxiety Disorder-7 (GAD-7) Total Score at Week 6 | -5.7 Units on a scale | Standard Error 0.51 |
Secondary
Change From Baseline in HAM-A Total Score at Weeks 2 and 4
Change from baseline in HAM-A total score at Weeks 2 and 4 were reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13: normal range, 14-17: mild severity, 18-24: mild to moderate severity, 25-30: moderate to severe, and \>=31: severe. Negative change in score indicates improvement.
Time frame: Baseline, Week 2, and Week 4
Population: The EAS included all randomized participants who received at least 1 dose of study agent and had improvement in percent changes in HDRS17 total score \<25% from screening to baseline and HDRS-17 total score \>=18 at baseline. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HAM-A Total Score at Weeks 2 and 4 | Week 4 | -8.05 Units on a scale | Standard Error 0.616 |
| Placebo | Change From Baseline in HAM-A Total Score at Weeks 2 and 4 | Week 2 | -4.85 Units on a scale | Standard Error 0.511 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in HAM-A Total Score at Weeks 2 and 4 | Week 2 | -4.1 Units on a scale | Standard Error 0.505 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in HAM-A Total Score at Weeks 2 and 4 | Week 4 | -7.9 Units on a scale | Standard Error 0.603 |
Secondary
Change From Baseline in HAM-A Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6
Change from baseline in HAM-A total score in participants with a baseline HAM-A score \>=20 at Week 6 was reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13: normal range, 14-17: mild severity, 18-24: mild to moderate severity, 25-30: moderate to severe, and \>=31: severe. Negative change in score indicates improvement.
Time frame: Baseline and Week 6
Population: The analyzed population included participants of EAS who had baseline HAM-A Score of \>=20.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HAM-A Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6 | -10.6 Units on a scale | Standard Error 0.78 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in HAM-A Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6 | -10.9 Units on a scale | Standard Error 0.77 |
Secondary
Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Week 6
Change from baseline in HAM-A total score at Week 6 was reported. HAM-A is a 14-item scale designed to measure severity of anxiety-related symptoms in participants. Each question reflects a symptom of general anxiety, including physical anxiety and mental anxiety. Each item was rated on a 5-point scale ranged from 0 (not present) to 4 (maximum anxiety). The total score was sum of 14 items scores and it ranged from 0 (normal) to 56 (severe), where higher score indicated greater degree of anxiety symptom. The total score was categorized as 0-13: normal range, 14-17: mild severity, 18-24: mild to moderate severity, 25-30: moderate to severe, and \>=31: severe. Negative change in score indicates improvement.
Time frame: Baseline and Week 6
Population: The EAS included all randomized participants who received at least 1 dose of study agent and had improvement in percent changes in HDRS17 total score \<25% from screening to baseline and HDRS-17 total score \>=18 at baseline. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Week 6 | -10.4 Units on a scale | Standard Error 0.74 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Week 6 | -10.3 Units on a scale | Standard Error 0.72 |
Secondary
Change From Baseline in HDRS-17 Total Score at Weeks 2 and 4
Change From baseline in HDRS-17 total score at Weeks 2 and 4. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition (greater depression).
Time frame: Baseline, Week 2, and Week 4
Population: The EAS included all randomized participants who received at least 1 dose of study agent and had improvement in percent changes in HDRS17 total score \<25% from screening to baseline and HDRS-17 total score \>=18 at baseline. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HDRS-17 Total Score at Weeks 2 and 4 | Week 2 | -3.98 Units on a scale | Standard Error 0.47 |
| Placebo | Change From Baseline in HDRS-17 Total Score at Weeks 2 and 4 | Week 4 | -6.78 Units on a scale | Standard Error 0.546 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in HDRS-17 Total Score at Weeks 2 and 4 | Week 2 | -3.54 Units on a scale | Standard Error 0.465 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in HDRS-17 Total Score at Weeks 2 and 4 | Week 4 | -7.03 Units on a scale | Standard Error 0.536 |
Secondary
Change From Baseline in HDRS-17 Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6
Change from baseline in HDRS-17 total score in participants with a baseline HAM-A score \>=20 at Week 6 was reported. The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (range: 0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition (greater depression).
Time frame: Baseline and Week 6
Population: The analyzed population included participants of EAS who had baseline HAM-A Score of \>=20.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HDRS-17 Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6 | -8.8 Units on a scale | Standard Error 0.68 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in HDRS-17 Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6 | -9.8 Units on a scale | Standard Error 0.67 |
Secondary
Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 2 and 4
Change From baseline in PHQ-9 total score at Weeks 2 and 4. The PHQ-9 is a 9-item, Patient Reported Outcome (PRO) measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participants item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19) and Severe (20-27).
Time frame: Baseline, Week 2, and Week 4
Population: The EAS included all randomized participants who received at least 1 dose of study agent and had improvement in percent changes in HDRS17 total score \<25% from screening to baseline and HDRS-17 total score \>=18 at baseline. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 2 and 4 | Week 2 | -3.26 Units on a scale | Standard Error 0.461 |
| Placebo | Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 2 and 4 | Week 4 | -5.63 Units on a scale | Standard Error 0.557 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 2 and 4 | Week 2 | -2.84 Units on a scale | Standard Error 0.455 |
| JNJ-61393215 135 Milligrams (mg) | Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 2 and 4 | Week 4 | -5.71 Units on a scale | Standard Error 0.544 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events during the initiation of study drug up till follow-up period.
Time frame: Up to 8 weeks
Population: The safety analysis set included all randomized participants who received at least 1 dose of study agent.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability | 34 Participants |
| JNJ-61393215 135 Milligrams (mg) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability | 50 Participants |
Secondary
Plasma Protein Binding (PPB): Percentage of JNJ-61393215 Unbound
Percentage of JNJ-61393215 unbound was determined by using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. The protein binding was assessed by spiking plasma samples with radiolabeled JNJ-61393215.
Time frame: Predose and 1-4 hours post dose on Day 43
Population: Analysis population included participant who received JNJ-61393215 and for whom PPB assessment was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Protein Binding (PPB): Percentage of JNJ-61393215 Unbound | Day 43: 1-4 hours postdose | 4.15 Percentage of JNJ-61393215 unbound | Standard Deviation 1.58 |
| Placebo | Plasma Protein Binding (PPB): Percentage of JNJ-61393215 Unbound | Day 43: Predose | 2.52 Percentage of JNJ-61393215 unbound | Standard Deviation 0.776 |
Secondary
Total Plasma Concentration of JNJ-61393215
Total plasma concentration of JNJ-61393215 was reported. The concentrations of JNJ-61393215 were measured using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method.
Time frame: 1-4 hours postdose on Day 1; Predose and 1-4 hours post dose on Days 15, 29, and 43
Population: Analysis population included participant who received JNJ-61393215 and for whom at least one pharmacokinetic (PK) concentration was available. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Plasma Concentration of JNJ-61393215 | Day 1: 1-4 hours postdose | 4143 Nanograms per milliter (ng/mL) | Standard Deviation 2315 |
| Placebo | Total Plasma Concentration of JNJ-61393215 | Day 15: Predose | 3053 Nanograms per milliter (ng/mL) | Standard Deviation 1857 |
| Placebo | Total Plasma Concentration of JNJ-61393215 | Day 15: 1-4 hours postdose | 5638 Nanograms per milliter (ng/mL) | Standard Deviation 2362 |
| Placebo | Total Plasma Concentration of JNJ-61393215 | Day 29: Predose | 3104 Nanograms per milliter (ng/mL) | Standard Deviation 1839 |
| Placebo | Total Plasma Concentration of JNJ-61393215 | Day 29: 1-4 hours postdose | 5868 Nanograms per milliter (ng/mL) | Standard Deviation 2267 |
| Placebo | Total Plasma Concentration of JNJ-61393215 | Day 43: Predose | 3019 Nanograms per milliter (ng/mL) | Standard Deviation 1794 |
| Placebo | Total Plasma Concentration of JNJ-61393215 | Day 43: 1-4 hours postdose | 5897 Nanograms per milliter (ng/mL) | Standard Deviation 2288 |