Clinical trial NCT03227224: A Study to Evaluate the Efficacy and Safety of JNJ-42847922 as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
Official title: A Multicenter, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, Adaptive Dose-Finding Study to Evaluate the Efficacy and Safety of JNJ-42847922 as Adjunctive Therapy to Antidepressants in Adult Subjects With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-07-24
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the dose-response relationship of 2 doses of JNJ-42847922 before interim analysis, and potentially 3 doses based on interim analysis results, compared to placebo as adjunctive therapy to an antidepressant drug in improving depressive symptoms in participants with Major Depressive Disorder (MDD) who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI); and to assess the safety and tolerability of JNJ-42847922 compared to placebo as adjunctive therapy to an antidepressant in participants with MDD.

Detailed description: The study will investigate the antidepressant effects of a range of doses of JNJ-42847922 (seltorexant) (versus placebo), as adjunctive treatment to antidepressant drugs for treatment of MDD, and will assess the safety and tolerability of JNJ-42847922. The study will be conducted in 3 phases: a screening phase (up to 4 weeks), a double-blind treatment phase (6 weeks), and a post-treatment follow-up phase (2 weeks). Efficacy, safety, pharmacokinetic, and biomarker evaluations will be performed in the study at defined timepoints. The duration of the study will be up to approximately 12 weeks (84 days).

Eligibility criteria: Inclusion Criteria:

* Men or women of non-childbearing potential (WONCBP), aged 18 to 70 years (inclusive). A WONCBP is defined as: a).Postmenopausal: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. b). Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy. c). If reproductive status is questionable, additional evaluation should be considered
* Meet Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) diagnostic criteria for major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Structured Clinical Interview for DSM-5 Axis I Disorders- Clinical Trials Version (SCID-CT). In addition their major depressive episode must be deemed "valid" using the SCID Screening Questionnaire (SSQ) interview administered by remote, independent raters. The length of the current depressive episode must be less than or equal to (\<=) 18 months
* Have had an inadequate response to at least 1 but no more than 3 antidepressants, administered at an adequate dose and duration in the current episode of depression, as measured by the Massachusetts General Hospital-Antidepressant Treatment Response Questionnaire (MGH-ATRQ). An inadequate response is defined as less than (\<)50 percent (%) reduction in depressive symptom severity, as assessed by the MGH-ATRQ. An adequate trial is defined as an antidepressant treatment for at least 4 weeks at or above the minimum therapeutic dose specified in the MGH-ATRQ, for any particular antidepressant. The inadequate response must include the participant's current antidepressant treatment
* Participants receiving monotherapy treatment for depressive symptoms with one of the following selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants, in any formulation: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at or above the minimum therapeutic dose level) for at least 4 weeks, and for no greater than 12 months, at screening. Modification of an effective preexisting therapy should not be made for the explicit purpose of entering a subject into the study
* Have a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater than or equal to (\>=)25 (performed by independent, centralized remote raters) at screening and must not demonstrate a clinically significant improvement (that is, an improvement of greater than \[\>\]20% on their MADRS total score) from the screening to baseline visit
* Must be otherwise healthy on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening. If the results of the clinical laboratory tests are outside the normal reference ranges, the participant could be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator

Exclusion Criteria:

* Has a history of, or current signs and symptoms of, severe renal insufficiency (creatinine clearance \<30 milliliter per minute \[mL/min\]); moderate to severe hepatic insufficiency (Child-Pugh Score 7-9), significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic (including narcolepsy), hematologic, rheumatologic, immunologic or endocrine disorders (including uncontrolled hypo- or hyperthyroidism or diabetes, or insulin-dependent diabetes mellitus). Participants with non-insulin dependent diabetes mellitus who are well-controlled (hemoglobin A1C \[HbA1C\] \<=7.5% and fasting glucose \<126 milligram per deciliter \[mg/dL\] at screening) could be eligible to participate if otherwise medically healthy, and if on a stable regimen of glucose-lowering medications for at least 2 months prior to screening
* Has signs and symptoms of Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the hypothalamic-pituitary-adrenal (HPA) axis
* Has a history of lack of response to 3 or more adequate antidepressant treatments, as indicated by no or minimal (\<= 25% improvement in symptoms) when treated with an antidepressant of adequate dose (per MGH-ATRQ) and duration (at least 4 weeks)
* Has history or current diagnosis of a psychotic disorder, bipolar disorder, mental retardation, autism spectrum disorder, or borderline personality disorder, somatoform disorders, chronic fatigue syndrome or fibromyalgia
* Has any significant primary sleep disorder, including but not limited to obstructive sleep apnea, restless leg syndrome, or parasomnias

Primary outcomes:
measure: Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline to Week 6
measure: Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to Week 8
measure: Percentage of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Up to Week 8
measure: Change From Baseline in Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) at Day 8
timeFrame: Baseline and Day 8
measure: Change From Baseline in Vital Signs (SBP and DBP) at Day 22
timeFrame: Baseline and Day 22
measure: Change From Baseline in Vital Signs (SBP and DBP) at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in Vital Signs (SBP and DBP) at Endpoint (Week 6)
timeFrame: Baseline and Endpoint (Week 6)
measure: Change From Baseline in Vital Sign (Pulse Rate [PR]) at Day 8
timeFrame: Baseline and Day 8
measure: Change From Baseline in Vital Sign (PR) at Day 22
timeFrame: Baseline and Day 22
measure: Change From Baseline in Vital Sign (PR) at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in Vital Sign (PR) at Endpoint (Week 6)
timeFrame: Baseline and Endpoint (Week 6)
measure: Change From Baseline in Vital Sign (Temperature) at Day 8
timeFrame: Baseline and Day 8
measure: Change From Baseline in Vital Sign (Temperature) at Day 22
timeFrame: Baseline and Day 22
measure: Change From Baseline in Vital Sign (Temperature) at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in Vital Sign (Temperature) at Endpoint (Week 6)
timeFrame: Baseline and Endpoint (Week 6)
measure: Change From Baseline in Physical Examination (Waist Circumference) at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in Physical Examination (Body Weight) at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in Physical Examination (Body Mass Index [BMI]) at Day 42
timeFrame: Baseline and Day 42
measure: Percentage of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values Outside Pre-defined Limits
timeFrame: Up to Week 6
measure: Percentage of Participants With Most Severe Post-baseline Potentially Suicide-Related Category Using Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Week 8
measure: Change From Baseline in Sexual Functioning as Measured by Arizona Sexual Experiences Scale (ASEX) Score at Day 42
timeFrame: Baseline and Day 42
measure: Physician Withdrawal Checklist-20 (PWC-20) Total Score at Day 43
timeFrame: Day 43
measure: Physician Withdrawal Checklist-20 (PWC-20) Total Score From Day 49 to Day 56
timeFrame: Day 49 to Day 56
Secondary outcomes:
measure: Change From Baseline in the MADRS Total Score by Baseline Insomnia Severity Index (ISI) Score at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in ISI Total Score at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
measure: Percentage of Participants With Response on Depressive Symptoms Scale Based on MADRS Total Score
timeFrame: Day 42
measure: Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score
timeFrame: Day 42
measure: Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Day 42
timeFrame: Baseline and Day 42
measure: Percentage of Participants With Response on Anxiety Symptoms Scale Based on HAM-A Total Score
timeFrame: Day 42
measure: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
measure: Change From Baseline in the Sheehan Disability Scale (SDS) Score at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in the MADRS Total Score at Day 42 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress
timeFrame: Baseline and Day 42
measure: Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Days 8, 22 and 42
timeFrame: Baseline, Days 8, 22 and 42
measure: Plasma Concentrations of Seltorexant and Its Metabolites (M12 and M16)
timeFrame: Day 1: Between 0.25 hours (h) to 1.5 hour, 2 to 4 hours, and 6 to 8 hours post-dose; Day 8 (morning): 6 to 12 hours post evening dose of Day 7
measure: Change From Baseline in Depressive Symptoms Using the Patient Health Questionnaire 9-Item (PHQ-9) at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
measure: Change From Baseline in Anhedonia Using the Snaith-Hamilton Pleasure Scale (SHAPS) Score at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
measure: Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
measure: Change From Baseline in Fatigue Using the Patient Reported Outcome Measurement Information System-Fatigue (PROMIS-F) Short Form Subscale Score at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
measure: Change From Baseline in Severity of Depression Using the Patient Global Impression-Severity (PGI-S) Score at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
measure: Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Heath State Index Total Score at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
measure: Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Total Score at Endpoint (Up to Week 6)
timeFrame: Baseline and Endpoint (up to Week 6)
measure: Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form Score at DB Endpoint (Up to Week 6)
timeFrame: Baseline and DB Endpoint (Up to Week 6)
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: California Pharmaceutical Research Institute, Inc.
state: California
city: Chino
country: United States
facility: Catalina Research Institute
state: California
city: Lemon Grove
country: United States
facility: Synergy Clinical Research Center Of Escondido
state: California
city: Panorama City
country: United States
facility: Asclepes Research
state: California
city: San Diego
country: United States
facility: Sharp Mesa Vista Hospital
state: California
city: San Rafael
country: United States
facility: SF-Care, Inc
state: California
city: Torrance
country: United States
facility: Collaborative NeuroScience Network
state: California
city: Wildomar
country: United States
facility: Elite Clinical Trials
state: California
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach
state: Florida
city: Jacksonville
country: United States
facility: Clinical NeuroScience Solutions Inc
state: Florida
city: Lauderhill
country: United States
facility: Innovative Clinical Research Inc
state: Florida
city: Miami Springs
country: United States
facility: Galiz Research
state: Florida
city: Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
city: North Miami
country: United States
facility: Behavioral Clinical Research , Inc
state: Florida
city: Orlando
country: United States
facility: Clinical NeuroScience Solutions Inc
state: Florida
city: Orlando
country: United States
facility: Compass Research LLC
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Radiant Research, Inc.
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Atlanta
country: United States
facility: NeuroTrials Research, Inc.
state: Georgia
city: Chicago
country: United States
facility: Chicago Research Center
state: Illinois
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Joliet
country: United States
facility: Joliet Center for Clinical Research
state: Illinois
city: New York
country: United States
facility: Clinilabs
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Winston-Salem
country: United States
facility: Clinical Trials of America
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Canton
country: United States
facility: Neuro Behavioral Clinical Research
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: The Woodlands
country: United States
facility: Family Psychiatry of The Woodlands
state: Texas
city: Everett
country: United States
facility: Core Clinical Research
state: Washington
city: Burgas
country: Bulgaria
facility: Mental Health Center Prof. Dr. Ivan Temkov
city: Kardzhali
country: Bulgaria
facility: State Psychiatric Hospital Kardzhali
city: Lovech
country: Bulgaria
facility: State Psychiatric Hospital - Lovech
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski', EAD
city: Plovdiv
country: Bulgaria
facility: MC 'Hipokrat - N', EOOD
city: Rousse
country: Bulgaria
facility: Mental Health Center - Rousse
city: Sofia
country: Bulgaria
facility: MHC - Sofia, EOOD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - UMHAT Alexandrovska EAD
city: Sofia
country: Bulgaria
facility: Medical Center 'Doverie'
city: Sofia
country: Bulgaria
facility: Medical Center Intermedica, OOD
city: Targovishte
country: Bulgaria
facility: MHAT-Targovishte, AD
city: Tzarev Brod
country: Bulgaria
facility: State Psychiatric Hospital - Tzarev Brod
city: Varna
country: Bulgaria
facility: Diagnostic Consulting Center Mladost - M Varna
city: Veliko Tarnovo
country: Bulgaria
facility: Mental Health Center - Veliko Tarnovo EOOD
city: Helsinki
country: Finland
facility: Mederon Oy
city: Kuopio
country: Finland
facility: Savon Psykiatripalvelu
city: Oulu
country: Finland
facility: Oulu Mentalcare Oy
city: Rauma
country: Finland
facility: Satakunnan Psykiatripalvelu
city: Clermont Ferrand
country: France
facility: CHU Clermont-Ferrand - Hopital Gabriel Montpied
city: Douai
country: France
facility: Cabinet Medical des Drs Prizac-Desbonnet Scottez
city: Nimes Cedex
country: France
facility: CHU Nimes Hopital Caremeau
city: Paris
country: France
facility: Hopital Sainte Anne
city: Rennes Cedex
country: France
facility: Centre Hospitalier Guillaume Regnier
city: Bad Homburg
country: Germany
facility: Neurologische Praxis Dr. Schoell & Kollegen
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carcus Dresden
city: Schwerin
country: Germany
facility: Somni Bene GmbH
city: Bunkyo-ku
country: Japan
facility: Hongo Todaimae Mental Clinic
city: Fukuoka-shi
country: Japan
facility: Kuramitsu Hospital
city: Ichikawa-shi
country: Japan
facility: National Center for Global Health and Medicine Kohnodai hospital
city: Kanzaki-gun
country: Japan
facility: National Hospital Organization Hizen Psychiatric Center
city: Kashihara-shi
country: Japan
facility: Nara Medical University Hospital
city: Meguro-ku
country: Japan
facility: Senzoku Mental Clinic
city: Nakano-ku
country: Japan
facility: Heart Care Ginga Clinic
city: Omuta-shi
country: Japan
facility: Shiranui Hospital
city: Sagamihara-shi
country: Japan
facility: Seiwakai Yutaka Clinic
city: Setagaya-ku
country: Japan
facility: Sangenjaya Nakamura Mental Clinic
city: Shibuya-ku
country: Japan
facility: Yoyogi Mental Clinic
city: Shinagawa-ku
country: Japan
facility: Etoh Mental Clinic
city: Shinjuku-ku
country: Japan
facility: Nishi-Shinjuku Concieria Clinic
city: Shinjuku-ku
country: Japan
facility: Tamaki Clinic
city: Shinjuku-ku
country: Japan
facility: Shinjuku Research Park Clinic
city: Toshima-ku
country: Japan
facility: Ohwa Mental Clinic
city: Toshima-ku
country: Japan
facility: Sekino Hospital
city: Toshima-ku
country: Japan
facility: Jisenkai Hozumi Himorogi Clinic
city: Arkhangelsk
country: Russian Federation
facility: SHI Arkhangelsk Regional Clinical Psychiatric Hospital
city: Ekaterinburg
country: Russian Federation
facility: Sverdlov Regional Psychiatric Clinical Hospital
city: Moscow
country: Russian Federation
facility: City Clinical Psychiatric Hopsital 3
city: Moscow
country: Russian Federation
facility: FSI Moscow SRI of Psychiatry of Minzdravsocrazvitia
city: Moscow
country: Russian Federation
facility: Closed corporation 'Scientific Center of Personalized Psychiatry'
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University n.a. I.M. Sechenov
city: Omsk
country: Russian Federation
facility: Clinical Psychiatry Hospital n.a. N.N. Solodovnikov
city: Rostov-on-Don
country: Russian Federation
facility: Medical and Rehabilitation Research Center Phoenix
city: Saint-Petersburg
country: Russian Federation
facility: City Psychiatric Hospital of St. Nikolay Chudotvorets
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: St. Petersburg
country: Russian Federation
facility: St-Petersburg Bekhterev Psychoneurological Research Institute
city: Tomsk
country: Russian Federation
facility: Research Institute of Mental Health
city: Ivano-Frankivsk
country: Ukraine
facility: CNCE'Precarpathian Regional Clinical Mental Health Center Ivano-Frankivsk RC'
city: Kharkiv
country: Ukraine
facility: Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'
city: Kyiv
country: Ukraine
facility: Cnce 'Kyiv City Psychoneurological Hospital #2' of Executive Body of Kyiv City Council (Kcsa)
city: Lviv
country: Ukraine
facility: CNCE of the Lviv Regional Council 'Lviv Regional Clinical Psychiatric Hospital'
city: Odesa
country: Ukraine
facility: CI Odesa Regional Medical Center of Mental Health
city: Oleksandrivka
country: Ukraine
facility: CNCE Odesa regional psychiatric hospital #2 Odesa regional council
city: Poltava
country: Ukraine
facility: Poltava O.F. Maltsev RC Psychiatric Hospital Dept #9 (Ad-P Dept) HSEIU Ukrainian MSA
city: Ternopil
country: Ukraine
facility: Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU
city: Vinnytsia
country: Ukraine
facility: CI O.I. Yuschenko VRPsH Depts #7 & #10 M.I. Pyrogov VNMU
city: Vinnytsia
country: Ukraine
facility: CNCE 'Vinnytsya RC Psychoneurological Hospital n.a. O.I. Yushchenko Vinnytsya RC'
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Savitz A, Wajs E, Zhang Y, Xu H, Etropolski M, Thase ME, Drevets WC. Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study. Int J Neuropsychopharmacol. 2021 Dec 8;24(12):965-976. doi: 10.1093/ijnp/pyab050.