Clinical trial NCT03559192: A Study to Explore the Efficacy of JNJ-67953964 in the Treatment of Depression
Official title: A Phase 2a Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multi-center Study Investigating the Efficacy, Safety, Tolerability and Pharmacokinetics of JNJ-67953964 in Subjects With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-06-18
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of JNJ-67953964 compared to placebo when administered as adjunctive treatment in participants with Major Depressive Disorder (MDD) partially responsive to selective serotonin reuptake inhibitor/ serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) treatment in terms of reduction of symptoms of depression, as assessed by the change from baseline on the Montgomery Asberg Depression Rating Scale (MADRS) in non-responders during the placebo lead-in period.


Eligibility criteria: Inclusion Criteria:

* Have a Body Mass Index (BMI) between 18 and 35 kilogram per meter square (kg/m\^2) inclusive (BMI = weight/height\^2)
* Participants must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and baseline
* Participants must have a primary Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnosis of Major Depressive Disorder (MDD)

  1. The current episode should be less than 18 months
  2. Participants should be currently treated with an SSRI or SNRI at an adequate dose and for at least 6 weeks but no more than 12 months
  3. Have a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater than or equal to (\>=) 25 at screening
* 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:

* History of documented gastric disease (including documented peptic ulcer disease, gastritis, upper gastrointestinal \[GI\] bleeding, esophagitis, or any GI precancerous condition), current clinically evident GI complaints
* Chronic use of a proton pump inhibitors (PPIs). History of incidental use of PPIs is allowed but should have been stopped at least 4 weeks before screening. A history of chronic nonsteroidal anti-inflammatory drug (NSAID) or aspirin use. (Low dose aspirin for example in cardiovascular disease prevention is allowed)
* Has a history of alcohol use disorder within the past year
* Has failed (no more than 25 percent \[%\] response on Antidepressant Treatment History Questionnaire \[ATRQ\]) three or more antidepressant treatments including the current Selective serotonin reuptake inhibitor/ serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) during the current depressive episode despite an adequate dose (per ATRQ) and duration (at least 6 weeks)
* Has signs or symptoms of Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the hypothalamus pituitary adrenal (HPA) axis
* Participant has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 3 months before the planned first dose of study drug or has participated in any interventional clinical studies on MDD in the previous 1 year or is currently enrolled in an interventional study
* Has one or more of the following diagnoses:

  1. A primary DSM (5th edition) diagnosis of generalized anxiety disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD). Participants with comorbid GAD, social anxiety disorder (SAD), or panic disorder for whom MDD is considered the primary diagnosis are not excluded
  2. A current diagnosis or diagnosis in the past 1 year of psychotic disorder, MDD with psychosis, anorexia nervosa or bulimia nervosa, chronic fatigue syndrome, bipolar disorder (BD), mental retardation, antisocial or borderline personality disorder, autism spectrum disorder
* Has a current or recent history of clinically significant suicidal ideation within the past 6 months, corresponding to a score of 4 (active suicidal ideation with some intent to act, without specific plan) or 5 (active suicidal ideation with specific plan and intent) for ideation on the Colombia suicide severity rating scale (C-SSRS), or a history of suicidal behavior within the past 1 year
* Ongoing psychological treatments (example, Cognitive Behavior Therapy, Interpersonal Psychotherapy, Psychodynamic Psychotherapy, etcetera \[etc.\]), initiated within 1 month prior to the screening phase. A participant who has been receiving ongoing psychological treatment for a period of greater than 1 month from the screening visit is eligible, if the investigator deems the psychological treatment to be of stable duration and frequency
* Participant has a history of substance use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before screening. Mild cases can be reviewed on a case by case basis. Participants who have completed a treatment for (alcohol) addiction more than 1 year prior to first dose administration, may be included if the risk of relapse is considered minimal, total duration of alcohol use disorder was less than a year, and no significant abnormalities are shown in clinical laboratory or other pre-dose safety assessments
* Participant has used:

  1. Monoamine oxidase inhibitors (MAOIs) within 12 weeks before screening
  2. St. John's wort, ephedra, ginkgo, ginseng, or kava within 2 weeks before screening
  3. Antipsychotic drugs (D2-antagonists) within 2 weeks before screening. However, Seroquel (quetiapine) in a dose less than or equals to (\<=)100 milligram (mg) is allowed when used in a stable dose for at least 8 weeks prior to screening. Quetiapine treatment should be continued unchanged during the study
  4. Opioids within 2 weeks before screening
  5. Psychostimulants such as methylphenidate or dextroamphetamine within 2 weeks before screening
  6. Psychotropics with antidepressant effects such as atomoxetine or thyroid supplementation, in addition to their SSRI or SNRI treatment within 2 weeks before screening
* Participant is unable to stop the following medication from the baseline visit (Visit 2) and throughout the study (tapering during screening period allowed): Any hypnotics including but not limited to: i. Benzodiazepines when used only as needed (PRN) are not allowed ii. Sedating antihistamines, including chronic use of diphenhydramine iii. Continuous use of zolpidem, zoplicon, eszopiclone and ramelteon. Note: Nonbenzodiazepines sleep aids (including: zolpidem, zaleplon, and eszopliclone) are allowed on an as needed (PRN) basis during the study but NOT within 24 hours before being in the clinic and not more than 2 nights in a row iv. S-adenosyl methionine (SAMe) v. Melatonin, agomelatine
* Has received any prior treatment with electroconvulsive therapy, vagal nerve stimulation, or a deep brain stimulation device or treatment with ketamine or esketamine for MDD

Primary outcomes:
measure: Change From Treatment Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Treatment Week 6 in Participants Who Were Non-Responders During Placebo Lead-in Period
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
Secondary outcomes:
measure: Change From Treatment Baseline in MADRS Total Score at Treatment Week 6
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) During DB Treatment Period
timeFrame: Up to Week 6
measure: Change From Treatment Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score at Treatment Week 6 (eITT Population)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Change From Treatment Baseline in SHAPS Total Score at Treatment Week 6 (fITT)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Change From Treatment Baseline in Clinical Global Impression - Severity (CGI-S) Score at Treatment Week 6 (eITT Population)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Change From Treatment Baseline in CGI-S Score at Treatment Week 6 (fITT Population)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Change From Treatment Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Treatment Week 6 (eITT Population)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Change From Treatment Baseline in SMDDS Total Score at Treatment Week 6 (fITT Population)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
timeFrame: Treatment Week 6
measure: Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
timeFrame: Treatment Week 6
measure: Change From Treatment Baseline in Hamilton Anxiety Scale 6 (HAM-A6) Total Score at Treatment Week 6 (eITT Population)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Change From Treatment Baseline in HAM-A6 Total Score at Treatment Week 6 (fITT)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Change From Treatment Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) Score at Treatment Week 6 (eITT Population)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Change From Treatment Baseline in SIGH-A Score at Treatment Week 6 (fITT Population)
timeFrame: Treatment Baseline up to Week 6 of DB-treatment period
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-67953964
timeFrame: Week 1: Day 29, Week 3: Day 43, Week 6 (Day 64)
measure: Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC[0-24h]) of JNJ-67953964
timeFrame: 0 to 24 hours Post dose on Week 1: Day 29, Week 3: Day 43, Week 6: Day 64
measure: Area Under Plasma Concentration-Time Curve at Steady State (AUCss) of JNJ-67953964
timeFrame: Week 1: Day 29, Week 3: Day 43, Week 6: Day 64
measure: Predose (Trough) Plasma Concentration (C0h) of JNJ-67953964
timeFrame: Predose on Week 1: Day 29, Week 3: Day 43, Week 6: Day 64
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Noble Clinical Research
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners
state: Arkansas
city: Glendale
country: United States
facility: Behavioral Research Specialists LLC
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Riverside
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Marcos
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Upland
country: United States
facility: Pacific Clinical Research Medical Group
state: California
city: Miami Springs
country: United States
facility: Galiz Research
state: Florida
city: Miami
country: United States
facility: Innova Clinical Trials
state: Florida
city: Orlando
country: United States
facility: APG Research LLC
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: Atlanta
country: United States
facility: Atlanta Behavioral Research, LLC
state: Georgia
city: Chicago
country: United States
facility: Chicago Research Center
state: Illinois
city: Skokie
country: United States
facility: Psychiatric Medicine Associates LLC
state: Illinois
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Princeton
country: United States
facility: Princeton Medical Institute
state: New Jersey
city: Brooklyn
country: United States
facility: Integrative Clinical Trials LLC
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioural Associates
state: New York
city: Hickory
country: United States
facility: Clinical Trials of America
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals, LLC
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Clinical NeuroScience Solutions Inc
state: Tennessee
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Berlin
country: Germany
facility: Emovis GmbH
city: Schwerin
country: Germany
facility: Somni Bene GmbH
city: Chisinau
country: Moldova, Republic of
facility: ARENSIA
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Psychiatric Hospital
city: Moscow
country: Russian Federation
facility: Clinical Psychiatric Hospital #3 Named After V.A. Gilyarovsky
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Psychiatric Hospital #1
city: Rostov-on-Don
country: Russian Federation
facility: Medical and Rehabilitation Research Center Phoenix
city: Saratov Region
country: Russian Federation
facility: Engels psychiatric hospital
city: Saratov
country: Russian Federation
facility: SHI 'Saratov City Clinical Hospital 2 n.a V.I. Razumovsky
city: Saratov
country: Russian Federation
facility: Saratov Regional Psychiatric hospital named after St. Sofia
city: St-Petersburg
country: Russian Federation
facility: City Psychiatric hospital 7 named after I.P.Pavlov
city: St-Petersburg
country: Russian Federation
facility: Psychoneurological dispensary 1
city: St. Petersburg
country: Russian Federation
facility: St-Petersburg Bekhterev Psychoneurological Research Institute
city: Tomsk
country: Russian Federation
facility: Research Institute of Mental Health
city: Glevakha
country: Ukraine
facility: MNCE of Kyiv RC Regional Psychiatric and Narcological Medical Association
city: Kharkiv
country: Ukraine
facility: Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'
city: Kherson
country: Ukraine
facility: CNPE'Kherson Regional Institution of Mental Care'of Kherson Regional Council
city: Kyiv
country: Ukraine
facility: Cnce 'Kyiv City Psychoneurological Hospital #2' of Executive Body of Kyiv City Council (Kcsa)
city: Nove
country: Ukraine
facility: Mnpe 'Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council'
city: Smila
country: Ukraine
facility: CNCE 'Cherkasy Regional Psychiatric Hospital of Cherkasy Regional Council'
city: Barnsley
country: United Kingdom
facility: MAC Clinical Research
city: Blackpool
country: United Kingdom
facility: MAC Clinical Research
city: Liverpool
country: United Kingdom
facility: MAC Clinical Research
city: London
country: United Kingdom
facility: Hammersmith Medicines Research Ltd
city: Manchester
country: United Kingdom
facility: MAC Clinical Research
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: