A Study to Investigate the Antidepressant Mechanism-of-action of JNJ-42847922 in Participants With Major Depressive Disorder

NCT03374475 | Completed Phase 1 FDA Drug

• 3 other identifiers: CR1083822017-002633-2842847922MDD1009
• Study Type: interventional
• Target: 140
• Locations: 5 countries
• Sites: 14

Brief Summary

The purpose of this study is to explore if the magnitude of treatment effect (JNJ-42847922; placebo) on symptoms of depression (as measured by Hamilton rating scale for depression-17 \[HDRS17\], Sleep item-adjusted HDRS17, Anxiety/somatization factor score and the 6-item subscale from HDRS17 \[HAM-D6\]) differs across different levels of hyper-arousal status (characterized by Sleep parameters, ruminative response scale \[RRS\], Sleep and Worry visual analogue scale \[VAS\], quantitative electro-encephalography \[qEEG\], heart rate variability \[HRV\] and others).

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Total Score

  The HDRS17 is a Clinician-Administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a total score range of 0 to 52. It is the most widely used symptom severity measure for depression. 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 uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Total score will be calculated by summing up the individual item score. The higher the score, the more severe the depression.

  Baseline up to Day 57

• Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Sleep Item-Adjusted Total Score

  The HDRS17 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. It is the most widely used symptom severity measure for depression. 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 uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. HDRS17 Sleep Item-Adjusted is derived from the HDRS17 scale excluding the 3 sleep items (4, 5, and 6) from the total score.

  Baseline up to Day 57

• Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Anxiety/Somatization Factor Score

  The HDRS17 anxiety/somatization factor derived from Cleary and Guy's factor analysis of the HDRS scale, includes six items from the original 17-item version: the items for psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Anxious depression is often defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, as reflected in an anxiety/ somatization factor score greater than or equal to (\>=) 7. The score ranges from 0 to 18, with higher scores indicating greater severity of symptoms.

  Baseline up to Day 57

• Change From Baseline in 6 Item Subscale From HDRS17 (HAM-D6) Score

  The 6-Item Hamilton Depression Scale (HAMD-6), derived by the sum of HAMD-17 items (the six items in the HAM-D6 are: depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and general somatics \[tiredness and pains\]), evaluates "core" symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe). The higher the score, the more severe the depression.

  Baseline up to Day 57

Secondary Outcomes (10)

• Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16)

  Baseline up to Day 67

• Association Between Major Depressive Disorder (MDD) Symptoms and Signals of Hyper-Arousal

  Baseline up to Day 67

• Performance Score on a Cognitive Test Battery Evaluated by Symbol Digit Matching Test (SDMaT)

  Baseline

• Performance Score on a Cognitive Test Battery Evaluated by Word List Recall Test (WLRT)

  Baseline

• Performance Score on a Cognitive Test Battery Evaluated by Trail Making Test Form B (TMT-B)

  Baseline

Study Arms (3)

Lead-in period: Placebo

PLACEBO COMPARATOR

Participants who successfully complete the baseline examination visit at the clinical site/unit, will be treated with placebo (2 capsules taken orally) for the duration of the lead-in period which will last up to 3 weeks. Investigators and participants will be blinded to exact duration of each participant-specific lead-in period throughout the study.

Drug: Placebo

Treatment period: JNJ-42847922 or Placebo

EXPERIMENTAL

Placebo lead-in period responders and non-responders will be randomized to receive either placebo or 20 milligram (mg) JNJ-42847922 or 40 mg JNJ-42847922 for 5 Weeks. Participants will swallow JNJ-42847922 20 mg (2\*10-mg capsules) or JNJ-42847922 40 mg (2\*20-mg capsules) or 2 matching placebo capsules once daily for 5 Weeks.

Drug: JNJ-42847922 20mg; Drug: JNJ-42847922 40mg; Drug: Placebo

Withdrawal period: Placebo

PLACEBO COMPARATOR

Participants who will complete the treatment period prior to the end of Week 8 will enter the withdrawal period where they will be treated with placebo (2 capsules taken orally) for the remaining time of the double-blind phase of the study. Investigators and participants will be blinded to exact duration of each participant-specific withdrawal period.

Drug: Placebo

Interventions

JNJ-42847922 20mg DRUG

Participants will swallow 20 mg (2\*10 mg) JNJ-42847922 capsule orally for 5 weeks during treatment period.

Treatment period: JNJ-42847922 or Placebo

JNJ-42847922 40mg DRUG

Participants will swallow 40 mg (2\*20 mg) JNJ-42847922 capsule orally for 5 weeks during treatment period.

Treatment period: JNJ-42847922 or Placebo

Placebo DRUG

All participants will receive matching placebo capsule during lead in period, treatment period and withdrawal period.

Lead-in period: Placebo; Treatment period: JNJ-42847922 or Placebo; Withdrawal period: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Population specific: Participant must meet Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-5) diagnostic criteria for MDD (international classification of diseases \[ICD\]-code F32.x and F33.x), without psychotic features, and confirmed by the Mini International Neuropsychiatric Interview (MINI) 7.0; have a Montgomery Asberg Depression Rating Scale (MADRS) total score greater than or equal to (\>=) 25 at screening and must not demonstrate a clinically significant change (that is, an improvement of greater than (\>) 20 percent (%) on their MADRS total score) from the screening to the second completion of MADRS by telephone at most 4 days before the baseline visit; Not currently receiving antidepressant drug therapy for \>= 2 weeks before screening
• Men who are sexually active with a women of childbearing potential (WOCBP) and have not had a vasectomy must agree to use a barrier method of birth control
• A woman of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 3 months after receiving the last dose of study drug

You may not qualify if:

• Has failed more than 2 treatments (no more than 20 percent (%) response) with a differing pharmacological mode of action despite an adequate dose and duration during a previous, or the current depressive episode
• Has a diagnosis of Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the Hypothalamus pituitary adrenal (HPA) axis
• Is pregnant or breast feeding
• Participant has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 60 days before the planned first dose of study drug, or has participated in 2 or more interventional clinical studies in the previous 1 year, or is currently enrolled in an interventional study
• Participant is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
• Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (14)

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

Artemis Institute for Clinical Research

San Marcos, California, 92078, United States

Location

Qps-Mra, Llc

Miami, Florida, 33143, United States

Location

SGS Phase 1 Unit AZ St-Maarten

Mechelen, 2800, Belgium

Location

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

Charite Research Organisation GmbH

Berlin, 10117, Germany

Location

Emovis GmbH

Berlin, 10629, Germany

Location

Fraunhofer-Institut für Toxikologie und Experimentelle Medizin

Hanover, 30625, Germany

Location

Somni Bene GmbH

Schwerin, 19053, Germany

Location

Centre for Human Drug Research

Leiden, 2333 CL, Netherlands

Location

MAC Clinical Research

Blackpool, FY2 0JH, United Kingdom

Location

MAC Clinical Research

Liverpool, L34 1BH, United Kingdom

Location

Hammersmith Medicines Research

London, NW10 7EW, United Kingdom

Location

MAC Clinical Research

Manchester, M13 9NQ, United Kingdom

Location

Related Publications (1)

• Mesens S, Kezic I, Van Der Ark P, Etropolski M, Pandina G, Benes H, Savitz A, Drevets WC. Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial. Mol Psychiatry. 2025 Jun;30(6):2427-2435. doi: 10.1038/s41380-024-02846-5. Epub 2024 Dec 11.

  PMID: 39663378 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

seltorexant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: December 15, 2017
• Study Start: January 5, 2018
• Primary Completion: April 29, 2019
• Study Completion: April 29, 2019
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

NL (1); BE (2); DE (4); US (3); GB (4)