A Study of JNJ-61393215 in the Treatment of Depression

Study Overview
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Brief Summary
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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.

Official Title
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Double-Blind, Placebo-Controlled, Multi-Center Study Investigating the Efficacy, Safety, and Tolerability of JNJ-61393215 as Adjunctive Treatment in Adults With Major Depressive Disorder With Anxious Distress With Suboptimal Response to Standard Antidepressants

Conditions
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Major Depressive Disorder With Anxious Distress

Intervention / Treatment
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* Drug: JNJ-61393215
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-61393215 135 milligram (mg)<br>Participants will receive JNJ-61393215 135 mg (3*45 mg capsules) orally once daily for 6 weeks along with the prescribed standard oral antidepressants (without dose change) throughout the study. | Drug: JNJ-61393215<br>* JNJ-61393215 will be administrated orally.<br>* Other names: Orexin-1;|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo for 6 weeks along with the prescribed standard oral antidepressants (without dose change) throughout the study. | Drug: Placebo<br>* Matching placebo will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 6 | 
| 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. | Baseline, Week 2, and Week 4 | 
| 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). | Baseline and Week 6 | 
| 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. | Baseline and Week 6 | 
| 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). | Baseline and Week 6 | 
| 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). | Baseline, Week 2, and Week 4 | 
| 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). | Baseline, Week 2, and Week 4 | 
| 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. | Up to 8 weeks | 
| 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. | 1-4 hours postdose on Day 1; Predose and 1-4 hours post dose on Days 15, 29, and 43 | 
| 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. | Predose and 1-4 hours post dose on Day 43 |