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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

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ClinicalTrials.gov Identifier: NCT03227224
Recruitment Status : Completed
First Posted : July 24, 2017
Last Update Posted : January 28, 2019
Sponsor:
Collaborator:
Minerva Neurosciences
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Depressive Disorder, Major Drug: Placebo Drug: JNJ-42847922 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 287 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 16, 2017
Actual Primary Completion Date : January 12, 2019
Actual Study Completion Date : January 19, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants will receive 2 placebo capsules matching JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).
Drug: Placebo
Participants will receive 2 placebo capsules matching JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).

Experimental: JNJ-42847922
Participants will receive 2 capsules of JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).
Drug: JNJ-42847922
Participants will receive 2 capsules of JNJ-42847922 once daily orally from Day 1 to Day 41 (Week 6).
Other Names:
  • MIN-202;
  • Seltorexant




Primary Outcome Measures :
  1. Primary Efficacy Parameter: Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline, Week 6 ]
    MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item 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.

  2. Primary Safety Parameter: Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to Week 8 ]
    Safety evaluations are not powered for this study. An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

  3. Primary Safety Parameter: Suicidal Ideation Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to Week 8 ]
    Safety evaluations are not powered for this study. C-SSRS is a clinician rated assessment of suicidal behavior and/or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 'yes/no' items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Only items with yes responses are listed. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.

  4. Primary Safety Parameter: Sexual Functioning Measured by the Arizona Sexual Experiences Scale (ASEX) [ Time Frame: Up to Week 6 ]
    Safety evaluations are not powered for this study. The ASEX is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction.

  5. Primary Safety Parameter: Potential Withdrawal Effects Measured By the Physician Withdrawal Checklist (PWC) [ Time Frame: Week 6 to 8 ]
    Safety evaluations are not powered for this study. The PWC (20 items; PWC-20) is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition.


Secondary Outcome Measures :
  1. Change From Baseline Through Week 6 in the MADRS Total Score in Participants With Baseline Insomnia Severity Index (ISI) Score Greater Than or Equal to (>=)15 Versus Participants With Baseline ISI Score Less Than (<)15 [ Time Frame: Baseline through Week 6 ]
    The ISI is a commonly used, 7-item psychometrically validated measure used to rate insomnia with a score: 0-7=no clinically significant insomnia; score 8-14=sub-threshold insomnia; score 15-21=moderate insomnia, and score 22-28=clinically severe insomnia.

  2. Change From Baseline in ISI Score Category at Week 6 [ Time Frame: Baseline, Week 6 ]
    The ISI is a commonly used, 7-item psychometrically validated measure used to rate insomnia with a score: 0-7=no clinically significant insomnia; score 8-14=sub-threshold insomnia; score 15-21=moderate insomnia, and score 22-28=clinically severe insomnia. The change in ISI score category from baseline at Week 6 will be evaluated.

  3. Percentage of Participants With Response on Depressive Symptoms Scale Based on Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Week 6 ]
    Responders are defined as participants with a >=50 percent (%) improvement in the MADRS total score from baseline at Week 6.

  4. Percentage of Participants With Remission of Depressive Symptoms Based on Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Week 6 ]
    Participants with a MADRS total score of less than or equal to (<=)8, <=10, and <=12 at Week 6 will be considered as remitters.

  5. Change From Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Week 6 [ Time Frame: Baseline, Week 6 ]
    HAM-A is a 14-item scale designed to measure anxiety in individuals. Each question reflects a symptom of anxiety and physical as well as mental symptoms are represented. The answers range from 0 (a complete lack of that symptom) to 4 (a very severe show of anxiety with that symptom). The total score ranges from 0 to 56, where higher score indicates worsening.

  6. Percentage of Participants With Response on Anxiety Symptoms Scale Based on Hamilton Anxiety Rating scale (HAM-A) [ Time Frame: Week 6 ]
    Participants with a >=50 percent (%) improvement in the HAM-A total score from baseline at Week 6, will be considered as responders.

  7. Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 6 [ Time Frame: Baseline, Week 6 ]
    The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of illness exhibited by a participant, rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Higher scores indicate worsening.

  8. Change From Baseline in the Sheehan Disability Scale (SDS) at Week 6 [ Time Frame: Baseline, Week 6 ]
    The SDS is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The scores for the first 3 items are summed to create a total score of 0-30 where a higher score indicates greater impairment. It also has 1 item on days lost from school or work and 1 item on days when underproductive.

  9. Change From Baseline in the MADRS Total Score at Week 6 in Participants With Major Depressive Disorder (MDD) With Anxious Distress Versus Participants With MDD Without Anxious Distress [ Time Frame: Baseline, Week 6 ]
    The change in MADRS total score for the subpopulations with and without anxious distress will be determined.

  10. Change From Baseline in Salivary Cortisol Levels, Measured Upon Awakening at Weeks 2, 4, and 6 [ Time Frame: Baseline, Weeks 2, 4, and 6 ]
    Exposure on the hypothalamic-pituitary-adrenal (HPA) axis in participants with MDD will be evaluated by assessing change in salivary cortisol levels.

  11. Area Under the Plasma Concentration-Time Curve (AUC) [ Time Frame: Day 1: Between 15 minutes to 1.5 hour, 2 to 4 hours, and 6 to 8 hours post-dose; Day 8: 6 to 12 hours post evening dose of Day 7 ]
    AUC is the area under the plasma concentration-time curve observed during a dosing interval.

  12. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 1: Between 15 minutes to 1.5 hour, 2 to 4 hours, and 6 to 8 hours post-dose; Day 8: 6 to 12 hours post evening dose of Day 7 ]
    The Cmax is the maximum observed plasma concentration.

  13. Change From Baseline in Depressive Symptoms Using the Patient Health Questionnaire 9-Item (PHQ-9) at Week 6 [ Time Frame: Baseline, Week 6 ]
    The PHQ-9 is a 9-item, participant Reported Outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.

  14. Change From Baseline in Anhedonia Using the Snaith-Hamilton Pleasure Scale (SHAPS) at Week 6 [ Time Frame: Baseline, Week 6 ]
    The SHAPS is a 14-item, self-report instrument to assess hedonic capacity in adults with MDD. Each of the items has a set of 4 response categories-Definitely Agree (=1), Agree (=2), Disagree (=3), and Definitely Disagree (=4). A total score is created with either of the Disagree responses receiving a score of 1 and either of the Agree responses receiving a score of 0. The participant's item responses are summed to provide a total score ranging from 0 to 14. A higher total SHAPS score indicates higher levels of current anhedonia.

  15. Change From Baseline in Sleep Disturbance Using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form at Week 6 [ Time Frame: Baseline, Week 6 ]
    The PROMIS-SD Short Form subscale consists of a static 8 item questionnaire. It assesses the concepts of sleep initiation (2 items), quality of sleep (3 items), early morning feelings (2 items) and worrying about sleep (1 item). Five-point Likert scales are provided to capture the participant's impressions ranging from 'very poor' to 'very good' and 'not at all to 'very much'.

  16. Change From Baseline in Fatigue Using the PROMIS-Fatigue Short Form at Week 6 [ Time Frame: Baseline, Week 6 ]
    The PROMIS-Fatigue Short Form subscale consists of a static 8 item questionnaire. It assesses a range of symptoms from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Ratings are done on a 5-item Likert scale ranging from 'not at all' to 'very much' and 'never' to 'always'.

  17. Change From Baseline in Severity of Depression Using the Patient Global Impression-Severity (PGI-S) at Week 6 [ Time Frame: Baseline, Week 6 ]
    The PGI-S is a self-report scale to measure severity of illness (1=none, 2=mild, 3=moderate, 4=severe).

  18. Change From Baseline in Health Related Quality of Life and Utility Using the European Quality of Life (EuroQol) Group, 5 Dimension, 5 Level (EQ-5D-5L) Questionnaire at Week 6 [ Time Frame: Baseline, Week 6 ]
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: Mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems (Level 1 indicating no problem, Level 2 indicating slight problems, Level 3 indicating moderate problems, Level 4 indicating severe problems, and Level 5 indicating extreme problems). The EQ-VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine).

  19. Change From Baseline in Work Productivity and Limitations Using the Work Limitations Questionnaire (WLQ) Short Form at Week 6 [ Time Frame: Baseline, Week 6 ]
    The WLQ is a 8-item questionnaire self-report rating scale developed to measure the on-the-job impact of chronic health problems and/or treatment ("work limitations"). It comprises four dimensions of limitations: handling time, physical, mental-interpersonal, and output demands. Participants respond to each item with options ranging from 'Almost all of the time' to 'none of the time', or 'Does not apply to my job'. Each dimension of limitations will have a scale score ranging from 0 to 100 with lower score indicating low level of work limitations.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03227224


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Sponsors and Collaborators
Janssen Research & Development, LLC
Minerva Neurosciences
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03227224     History of Changes
Other Study ID Numbers: CR108281
42847922MDD2001 ( Other Identifier: Janssen Research & Development, LLC )
2015-005282-22 ( EudraCT Number )
First Posted: July 24, 2017    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Psychotropic Drugs