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

NCT ID: NCT03227224

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 287 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-16
• Study Completion Date: 2019-01-19

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).

Conditions

Depressive Disorder, Major

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Participants will receive 2 placebo capsules matching JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive 2 placebo capsules matching JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).

JNJ-42847922

Participants will receive 2 capsules of JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).

Group Type: EXPERIMENTAL

JNJ-42847922

Intervention Type: DRUG

Participants will receive 2 capsules of JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).

Interventions

Placebo

Participants will receive 2 placebo capsules matching JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).

Intervention Type: DRUG

JNJ-42847922

Participants will receive 2 capsules of JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).

Intervention Type: DRUG

Other Intervention Names

MIN-202; Seltorexant

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

California Pharmaceutical Research Institute, Inc.

Anaheim, California, United States

Catalina Research Institute

Chino, California, United States

Synergy Clinical Research Center Of Escondido

Lemon Grove, California, United States

Asclepes Research

Panorama City, California, United States

Sharp Mesa Vista Hospital

San Diego, California, United States

SF-Care, Inc

San Rafael, California, United States

Collaborative NeuroScience Network

Torrance, California, United States

Elite Clinical Trials

Wildomar, California, United States

Sarkis Clinical Trials

Gainesville, Florida, United States

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, United States

Clinical NeuroScience Solutions Inc

Jacksonville, Florida, United States

Innovative Clinical Research Inc

Lauderhill, Florida, United States

Qps-Mra, Llc

Miami, Florida, United States

Galiz Research

Miami Springs, Florida, United States

Behavioral Clinical Research , Inc

North Miami, Florida, United States

Clinical NeuroScience Solutions Inc

Orlando, Florida, United States

Compass Research LLC

Orlando, Florida, United States

Emory University

Atlanta, Georgia, United States

Radiant Research, Inc.

Atlanta, Georgia, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

NeuroTrials Research, Inc.

Atlanta, Georgia, United States

Chicago Research Center

Chicago, Illinois, United States

Great Lakes Clinical Trials

Chicago, Illinois, United States

Joliet Center for Clinical Research

Joliet, Illinois, United States

Clinilabs

New York, New York, United States

Richmond Behavioral Associates

Staten Island, New York, United States

Clinical Trials of America

Winston-Salem, North Carolina, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Neuro Behavioral Clinical Research

Canton, Ohio, United States

Midwest Clinical Research Center

Dayton, Ohio, United States

Suburban Research Associates

Media, Pennsylvania, United States

Family Psychiatry of The Woodlands

The Woodlands, Texas, United States

Core Clinical Research

Everett, Washington, United States

Mental Health Center Prof. Dr. Ivan Temkov

Burgas, , Bulgaria

State Psychiatric Hospital Kardzhali

Kardzhali, , Bulgaria

State Psychiatric Hospital - Lovech

Lovech, , Bulgaria

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, , Bulgaria

MC 'Hipokrat - N', EOOD

Plovdiv, , Bulgaria

Mental Health Center - Rousse

Rousse, , Bulgaria

MHC - Sofia, EOOD

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment - UMHAT Alexandrovska EAD

Sofia, , Bulgaria

Medical Center 'Doverie'

Sofia, , Bulgaria

Medical Center Intermedica, OOD

Sofia, , Bulgaria

MHAT-Targovishte, AD

Targovishte, , Bulgaria

State Psychiatric Hospital - Tzarev Brod

Tzarev Brod, , Bulgaria

Diagnostic Consulting Center Mladost - M Varna

Varna, , Bulgaria

Mental Health Center - Veliko Tarnovo EOOD

Veliko Tarnovo, , Bulgaria

Mederon Oy

Helsinki, , Finland

Savon Psykiatripalvelu

Kuopio, , Finland

Oulu Mentalcare Oy

Oulu, , Finland

Satakunnan Psykiatripalvelu

Rauma, , Finland

CHU Clermont-Ferrand - Hopital Gabriel Montpied

Clermont-Ferrand, , France

Cabinet Medical des Drs Prizac-Desbonnet Scottez

Douai, , France

CHU Nimes Hopital Caremeau

Nîmes, , France

Hopital Sainte Anne

Paris, , France

Centre Hospitalier Guillaume Regnier

Rennes, , France

Neurologische Praxis Dr. Schoell & Kollegen

Bad Homburg, , Germany

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Universitatsklinikum Carl Gustav Carcus Dresden

Dresden, , Germany

Somni Bene GmbH

Schwerin, , Germany

Hongo Todaimae Mental Clinic

Bunkyō City, , Japan

Kuramitsu Hospital

Fukuoka, , Japan

National Center for Global Health and Medicine Kohnodai hospital

Ichikawa-shi, , Japan

National Hospital Organization Hizen Psychiatric Center

Kanzaki-gun, , Japan

Nara Medical University Hospital

Kashihara-shi, , Japan

Senzoku Mental Clinic

Meguro-ku, , Japan

Heart Care Ginga Clinic

Nakano, , Japan

Shiranui Hospital

Omuta-shi, , Japan

Seiwakai Yutaka Clinic

Sagamihara-shi, , Japan

Sangenjaya Nakamura Mental Clinic

Setagaya-ku, , Japan

Yoyogi Mental Clinic

Shibuya-ku, , Japan

Etoh Mental Clinic

Shinagawa-ku, , Japan

Nishi-Shinjuku Concieria Clinic

Shinjuku-ku, , Japan

Tamaki Clinic

Shinjuku-ku, , Japan

Shinjuku Research Park Clinic

Shinjuku-ku, , Japan

Ohwa Mental Clinic

Toshima-ku, , Japan

Sekino Hospital

Toshima-ku, , Japan

Jisenkai Hozumi Himorogi Clinic

Toshima-ku, , Japan

SHI Arkhangelsk Regional Clinical Psychiatric Hospital

Arkhangelsk, , Russia

City Clinical Psychiatric Hopsital 3

Moscow, , Russia

FSI Moscow SRI of Psychiatry of Minzdravsocrazvitia

Moscow, , Russia

Closed corporation 'Scientific Center of Personalized Psychiatry'

Moscow, , Russia

First Moscow State Medical University n.a. I.M. Sechenov

Moscow, , Russia

Clinical Psychiatry Hospital n.a. N.N. Solodovnikov

Omsk, , Russia

Medical and Rehabilitation Research Center Phoenix

Rostov-on-Don, , Russia

City Psychiatric Hospital of St. Nikolay Chudotvorets

Saint Petersburg, , Russia

St-Petersburg Bekhterev Psychoneurological Research Institute

Saint Petersburg, , Russia

SHI 'Saratov City Clinical Hospital 2 n.a V.I. Razumovsky

Saratov, , Russia

Engels psychiatric hospital

Saratov Region, , Russia

Research Institute of Mental Health

Tomsk, , Russia

Sverdlov Regional Psychiatric Clinical Hospital

Yekaterinburg, , Russia

CNCE'Precarpathian Regional Clinical Mental Health Center Ivano-Frankivsk RC'

Ivano-Frankivsk, , Ukraine

Mnpe of Kharkiv Regional Council 'Regional Clinical Psychiatric Hospital #3'

Kharkiv, , Ukraine

Cnce 'Kyiv City Psychoneurological Hospital #2' of Executive Body of Kyiv City Council (Kcsa)

Kyiv, , Ukraine

CNCE of the Lviv Regional Council 'Lviv Regional Clinical Psychiatric Hospital'

Lviv, , Ukraine

CI Odesa Regional Medical Center of Mental Health

Odesa, , Ukraine

CNCE Odesa regional psychiatric hospital #2 Odesa regional council

Oleksandrivka, , Ukraine

Poltava O.F. Maltsev RC Psychiatric Hospital Dept #9 (Ad-P Dept) HSEIU Ukrainian MSA

Poltava, , Ukraine

Ternopil RCCPH Depts of Psychiatry #2 (m) & Psychiatry #4 (f) Ternopil I.Ya. Gorbachevskyi SMU

Ternopil, , Ukraine

CI O.I. Yuschenko VRPsH Depts #7 & #10 M.I. Pyrogov VNMU

Vinnytsia, , Ukraine

CNCE 'Vinnytsya RC Psychoneurological Hospital n.a. O.I. Yushchenko Vinnytsya RC'

Vinnytsia, , Ukraine

Countries

United States; Bulgaria; Finland; France; Germany; Japan; Russia; Ukraine

References

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.

Reference Type: DERIVED

PMID: 34324636 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

42847922MDD2001

Identifier Type: OTHER

Identifier Source: secondary_id

2015-005282-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108281

Identifier Type: -

Identifier Source: org_study_id