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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy of JNJ-55308942 compared to placebo on symptoms of depression in participants with bipolar disorder (BD) in a major depressive episode (MDE) at Week 6.

Official Title
-----------------
A Randomized, Stratified, Double-blind, Placebo-Controlled Study to Investigate the Efficacy, Safety and Tolerability of JNJ-55308942 in Bipolar Depression

Conditions
-----------------
Bipolar Disorder

Intervention / Treatment
-----------------
* Drug: JNJ-55308942
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a primary diagnostic and statistical manual of mental disorders (5th edition) (DSM-5) diagnosis of bipolar disorder (BD) (Type I or II) without current psychotic features, as confirmed by the mini international neuropsychiatric interview (MINI) Medically stable on the basis of physical examination, medical history, and vital signs performed at screening. Any abnormalities must be consistent with the underlying illness in the study population. This determination must be recorded in the participant's source documents and initialed by the investigator Have a body mass index (BMI) between 18.0 and 35.0 kilograms per meter square (kg/m^2) inclusive (BMI = weight/height^2) A woman of childbearing potential (WOCBP) must have a negative highly sensitive serum pregnancy test (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test before the first dose of study intervention Exclusion Criteria: Currently meets the DSM-5 criteria for Manic Episode (ME) on the MINI Received transcranial magnetic stimulation (TMS), any transcranial electrical stimulation, including transcranial direct current stimulation (tDCS), vagal nerve stimulation (VNS) and/or deep brain stimulation (DBS) within 6 weeks prior to randomization History of moderate to severe cannabis misuse according to DSM-5 criteria within 6 months before screening History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-55308942<br>Participants will receive a JNJ-55308942 capsule once daily for 6 weeks. | Drug: JNJ-55308942<br>* JNJ-55308942 capsules will be administered orally.<br>|
| Placebo Comparator: Placebo<br>Participants will receive a matching placebo capsule once daily for 6 weeks. | Drug: Placebo<br>* Matching placebo capsules will be administered orally.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | Change from baseline in MADRS total score at Week 6 will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score at Week 6 | Change from baseline in SHAPS total score at Week 6 will be reported. | Baseline and Week 6 | 
| Change from Baseline in MADRS Total Score at Week 6 (Genetic Subgroup Analysis) | Change from baseline in MADRS total score at Week 6 in participants who are heterozygous or homozygous for a specific single nucleotide polymorphism (SNP) (genetic subgroup analysis) will be reported. | Baseline and Week 6 | 
| Change from Baseline in MADRS Total Score at Week 6 (Diagnosis Subgroup Analysis) | Change from Baseline in MADRS total score at Week 6 in participants with bipolar disorder (BD) diagnostic subtypes (diagnosis subgroup analysis) will be reported. | Baseline and Week 6 | 
| Change from Baseline in MADRS Total Score at Week 6 (Biomarker Subgroup Analysis) | Change from baseline in MADRS total score at Week 6 in subgroups of participants with specific biomarker profiles (biomarker subgroup analysis) will be reported. | Baseline and Week 6 | 
| Number of Participants with Abnormalities in Vital Signs | Number of participants with abnormalities in vital signs (pulse/heart rate, systolic blood pressure [SBP], diastolic blood pressure [DBP], respiratory rate) will be reported. | Up to Week 8 | 
| Number of Participants with Abnormalities in Clinical Laboratory Tests | Number of participants with abnormalities in clinical laboratory tests (chemistry, hematology, urinalysis) will be reported. | Up to Week 8 | 
| Number of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. | Up to Week 8 | 
| Number of Participants with Abnormalities in Electrocardiograms (ECGs) | Number of participants with abnormalities in ECG will be reported. | Up to Week 8 | 
| Change from Baseline in Young Mania Rating Scale (YMRS) Score | Change from baseline in YMRS score will be reported. The YMRS is a rating scale used to assess manic symptoms. | Baseline up to Week 6 | 
| Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score | Change from baseline in C-SSRS score will be reported. | Baseline up to Week 8 | 
| Change from Baseline in Clinical Global Impression-Severity Scale (CGI-S) Score | Change from baseline in CGI-S scale score will be reported. | Baseline up to Week 6 | 
| Plasma Concentrations of JNJ-55308942 | Plasma samples will be analyzed to determine concentrations of JNJ-55308942 using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. | Days 1, 8, 15, 29, 43 | 
| Change from Baseline in Patient Reported Outcome Measurement (PROMIS) Score - Ability to Participate in Social Roles and Activities Scores | Change from baseline in PROMIS score- ability to participate in social roles and activity scores score will be reported. Participation in social roles and activities item bank assesses the perceived ability to perform one's usual social roles and activities. | Baseline, up to Week 6 | 
| Change from Baseline in Patient Health Questionnaire (PHQ-9) Score | Change from baseline in PHQ-9 will be reported. PHQ-9 score used to assess the severity of depression in the participants. | Baseline up to Week 6 | 
| Change from Baseline in Generalized Anxiety Disorder 7 (GAD-7) Score. | Change from baseline in GAD-7 score will be reported. | Baseline up to Week 6 | 
| Percentage of Participants with Response at Week 6 | Percentage of participants with response (greater than or equal to [>=] 50 percent [%] improvement in MADRS total score) at Week 6 will be reported. | Week 6 | 
| Number of Participants with Remission at Week 6 | Number of participants with remission (MADRS total score less than or equal to [<=] 12) at Week 6 will be reported. | Week 6 | 
| Change from Baseline in MADRS Total Score at Week 6 (Subgroup of Participants with Messenger Ribonucleic Acid [mRNA] Transcript Levels) | Change from baseline in MADRS total score at Week 6 in participants with levels of specific mRNA transcripts that exceed the median level will be reported. | Baseline and Week 6 | 
| Change from Baseline in MADRS Total Score at Week 6 (Mood Stabilizer Subgroup Analysis) | Change from baseline in MADRS total score at Week 6 in subgroup of participants with BD not taking any mood stabilizer or antipsychotic, taking a mood stabilizer alone, taking an antipsychotic alone, and taking a combination of a mood stabilizer and an antipsychotic (concomitant medication subgroup analysis) will be reported. | Baseline and Week 6 |