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A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy

Primary Purpose

Depressive Disorder, Major

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

JNJ-42847922

Placebo Matching to JNJ-42847922

Quetiapine XR

Placebo Matching to Quetiapine XR

Selective Serotonin Reuptake Inhibitor (SSRI)

Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

About this trial

This is an interventional treatment trial for Depressive Disorder, Major

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female of non-childbearing potential (WONCBP) outpatients, 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). 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 assessed 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, as specified in the MGH-ATRQ, for any particular antidepressant. The inadequate response must include the participant's current antidepressant treatment
Be receiving monotherapy treatment for depressive symptoms with 1 of the following selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (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 participant 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
Have a Body Mass Index (BMI) between 18 and 35 kilogram per meter square (kg/m^2) inclusive (BMI equal to [=] weight/height^2)
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 there are abnormalities, they must be consistent with the underlying illness in the study population. If the results of the clinical laboratory tests are outside the normal reference ranges, the participant may 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:

Have Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the hypothalamic-pituitary-adrenal (HPA) axis
Have a history of epilepsy, neuroleptic malignant syndrome (NMS) or Tardive Dyskinesia
Have a history of previous non-response to an adequate trial of quetiapine as an adjunctive treatment for MDD (adequate trial defined as >=150 mg for 4 weeks or more) and/or a history of lack of response to 3 or more adequate antidepressant treatments and/or a history or evidence of noncompliance with current antidepressant therapy
Have taken a known moderate or strong inhibitor/inducer of cytochrome P450 (CYP)3A4 and CYP2C9 or a dual inhibitor/inducer of CYP3A4 and CYP2C9 within 14 days (or after washout that is, duration of 5 times the drug's half-life) before the first study drug administration on Day 1 until the follow-up visit. Fluvoxamine is a moderate CYP2C9 inhibitor and a mild CYP3A inhibitor, and will not be excluded from the study
Have a history or current diagnosis of a psychotic disorder, bipolar disorder, intellectual disability, autism spectrum disorder, borderline personality disorder, somatoform disorders, or fibromyalgia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

JNJ-42847922

Quetiapine Extended-Release (XR)

Arm Description

Participants will receive 20 mg of JNJ-42847922 as a starting dose and matching placebo (1 capsule of 20 mg JNJ-42847922 and 1 capsule of matching placebo) once daily for 14 days. After Day 14, if needed, JNJ-42847922 dose can be increased to 40 mg (2*20 mg capsules) and flexible dose of JNJ-42847922 (20 or 40 mg) will be taken once daily until Day 167. Dose of JNJ-42847922 (20 or 40 mg) will be adjusted by investigator based on the participant's clinical response and tolerability. Participants will continue to take their baseline selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant as a part of background therapy (at the same dose, without change, every day and at approximately the same time as prior to entering the study) throughout the screening, double-blind, and follow-up phases.

Participants will receive 1 capsule of quetiapine XR 50 mg along with 1 capsule of matching placebo once daily for 2 days, followed by 1 capsule of quetiapine XR 150 mg along with 1 capsule of matching placebo once daily from Day 3 to Day 14. After Day 14, if needed, quetiapine XR dose can be increased to 300 mg (2*150 mg capsules) and flexible dose of quetiapine (150 or 300 mg) will be taken once daily until Day 167. Dose of quetiapine XR (150 or 300 mg) will be adjusted by investigator based on the participant's clinical response and tolerability. Participants will continue to take their baseline SSRI/SNRI antidepressant as a part of background therapy (at the same dose, without change, every day and at approximately the same time as prior to entering the study) throughout the screening, double-blind, and follow-up phases.

Outcomes

Primary Outcome Measures

Time to All-Cause Discontinuation of Study Drug

Time to all-cause discontinuation of study drug is defined as the number of days from the first dose of study drug to the last dose of study drug. Participants who completed double-blind treatment were not considered to have discontinued.

Secondary Outcome Measures

Percentage of Participants With Sustained Remission up to Week 24

Remission is defined as Montgomery-Asberg Depression Rating Scale (MADRS) total score of less than or equal to (<=) 12. A participant was defined as having achieved sustained remission if the MADRS total score was ≤12 at Week 12 and was sustained at Weeks 18 and 24. Participants with missing values at a given time point were imputed as non-evaluable for remission. 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 range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition.

Percentage of Participants With Sustained Response up to Week 24

A participant was defined as having achieved a sustained response if there was at least a 50% improvement from baseline in the MADRS total score at Week 12, and that response was maintained at Week 18 and Week 24. Participants who did not meet such criterion were considered as non-sustained responders. 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 range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition.

Change From Baseline in MADRS Total Score in Participants With Significant Insomnia (Baseline Insomnia Severity Index [ISI] Score >=15) Versus Those Without Significant Insomnia (Baseline ISI Score Less Than [<] 15) at Week 12

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 range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. The ISI has 7 questions, each rated on a 5-point Likert scale ranging from 0 to 4. The total score is calculated as the sum of the 7 items ranging from 0 to 28. Higher scores represent a more severe condition.

Change From Baseline in MADRS Total Score in Participants With Significant Insomnia (Baseline ISI Score >=15) Versus Those Without Significant Insomnia (Baseline ISI Score <15) at Week 18

Change From Baseline in MADRS Total Score in Participants With Significant Insomnia (Baseline ISIscore >=15) Versus Those Without Significant Insomnia (Baseline ISI Score 15) at Week 24

Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Weeks 12, 18, and 24

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. Each of the 14-items in the scale is scored on a 5-point scale, ranging 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 which is calculated by adding the scores of all 14 items, where 0-13 indicates normal range, 14-17 indicates mild severity, 18 -24: mild to moderate severity, 25 -30: moderate to severe, and >=31: severe. Higher score indicates worsening. Negative change in score indicates improvement.

Percentage of Participants With Weight Gain of >=7% of Baseline Body Weight at Week 24

Percentage of participants with weight gain of >=7% of baseline body weight at Week 24 were reported.

Percentage of Participants With Shifts in Triglycerides From Normal to High

Percentage of participants with shifts in triglycerides from normal to high (<150 milligrams per deciliter [mg/dL] at baseline to >=200 mg/dL at any post-baseline assessment) were reported.

Percentage of Participants With Shifts in Triglycerides From Borderline to High

Percentage of participants with shifts in triglycerides from borderline to high (>=150 to <200 mg/dL at baseline to >=200 mg/dL at any post-baseline assessment) were reported.

Percentage of Participants With Shifts in Triglycerides From Normal to Very High

Percentage of participants with shifts in triglycerides from normal to very high (<150 mg/dL at baseline to >=500 mg/dL at any post-baseline assessment) were reported.

Percentage of Participants With Shifts in Triglycerides From Borderline to Very High

Percentage of participants with shifts in triglycerides from borderline to very high (>=150 mg/dL to <200 mg/dL at baseline to >=500 mg/dL at any post-baseline assessment) were reported.

Percentage of Participants With Shifts in Triglycerides From High to Very High

Percentage of participants with shifts in triglycerides from high to very high (>=200 mg/dL to <500 mg/dL at baseline to >=500 mg/dL at any post-baseline assessment) were reported.

Percentage of Participants With Shifts in Fasting Blood Glucose From Normal to Borderline

Percentage of participants with shifts in fasting blood glucose from normal to borderline (<100 mg/dL at baseline to between >=100 and <126 mg/dL at any post-baseline assessment) were reported.

Percentage of Participants With Shifts in Fasting Blood Glucose From Borderline to High

Percentage of participants with shifts in fasting blood glucose from borderline to high (>=100 to <126 mg/dL at baseline to >=126 mg/dL at any post-baseline assessment) were reported.

Percentage of Participants With Shifts in Fasting Blood Glucose From Normal to High

Percentage of participants with shifts in fasting blood glucose from normal to high (<100 mg/dL at baseline to >=126 mg/dL at any post-baseline assessment) were reported.

Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale Score at Weeks 12 and 24

The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. 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. Negative change in score indicates improvement.

Change From Baseline in the Patient Global Impression Severity (PGI-S) Scale Score at Weeks 12 and 24

The PGI-S is a self-report scale to measure severity of illness (1=none, 2=mild, 3=moderate, 4=severe). Higher score indicates more illness severity. Negative change in score indicates improvement.

Change From Baseline in Quality of Life in Depression Scale (QLDS) Score at Weeks 12 and 24

The QLDS is a disease specific patient-reported outcome (PRO) designed to assess health related quality of life in participants with major depressive disorder (MDD). The instrument has a recall period of "at the present time", contains 34-items with "true"/"not true" response options. Each statement on the QLDS is given a score of "1" (adverse quality of life) or "0" good quality of life. All item scores are summed to give a total score that ranges from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. Negative change indicates improvement.

Change From Baseline in Patient Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 8a at Weeks 12 and 24

The PROMIS-SD Short Form 8a 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). Responses to each of the 8 items range from 1 to 5, and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS-SD indicate more of the concept measured (disturbed sleep). Negative change in score indicates improvement.

Change From Baseline in Patient Reported Outcomes Measurement Information System-Sleep Related Impairment (PROMIS-SRI) Short Form 8a at Weeks 12 and 24

The PROMIS-SRI Short Form 8a subscale consists of a static 8 item questionnaire and use five-point likert scale to capture the participant's impressions. It assesses sleep-related impairment over the past 7 days. Responses to each of the 8 items range from 1 (less impairment) to 5 (more impairment), and the range of possible summed raw scores is 8 to 40. Lower scores indicate less sleep related impairment. Negative change in score indicates improvement.

Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Score at Weeks 12 and 24

The SMDDS assesses participant-reported symptoms associated with MDD. This 16-item instrument has a 7-day recall period, and participants respond to each question using a rating scale between 0 ("Not at all" or "Never") to 4 ("Extremely" or "Always"). Before summing the items to create a total score, item 11 ("how often did you have a poor appetite") and item 12 ("how often did you over eat") are combined into a single score by selecting the highest severity on either item. The total score is then created by summing the responses on the 15 items. The total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology. Negative change in score indicates improvement.

Change From Baseline in Symbol Digit Modalities Test (SDMT) at Weeks 6, 12, and 24

SDMT is a widely used, paper-and-pencil assessment of complex scanning and visual tracking, requiring elements of attention, visuoperceptual processing, working memory, and cognitive/psychomotor speed. The test is viewed as a robust screening test for adult neuropsychological impairment and is sensitive to impairments in cognitive function associated with MDD. The SDMT measured the time to pair abstract symbols with specific numbers. The test included a coding key consisting of 9 abstract symbols, each paired with a number ranging from 1 to 9. Following the key, the participant was presented with randomly ordered symbols and was required to write the number corresponding to each symbol as fast as possible. The number of correct substitutions within 90 seconds was recorded and total score derived from the total number of correct responses with a minimum possible score of 0 and maximum of 110 where high scores indicate better outcome. Positive change in score indicates improvement.

Change From Baseline in Trail Making Test - Part B (TMT-Part B) at Weeks 6, 12, and 24

The TMT-Part B measures divided attention and executive function (tracking and sequencing). The participant is instructed to draw a line to connect a set of 25 consecutively numbered and lettered circles, alternating sequentially between numbers and letters (that is, 1 A 2 B). The participant is instructed to work as quickly as possible while still maintaining accuracy. Score included time (seconds) to completion and number of errors in performing the test which ranges from 0 (no errors) to 25 (more errors), where shorter time and less number of errors indicates better performance. The TMT-Part B is sensitive to cognitive decline associated with MDD. Negative change in score indicates improvement.

Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) at Weeks 6, 12, and 24

The HVLT-R measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0 -12); the total number of true-positive errors (0-12); and the recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher score indicates higher cognition.

Change From Baseline in Salivary Cortisol Levels as Measured at Home Upon Awakening and During the Evening at Weeks 6 and 24

Change from baseline in salivary cortisol levels as measured upon awakening and at home during the evening at Weeks 6 and 24 were reported.

Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were AEs with onset during the double-blind treatment phase or that were a consequence of a preexisting condition that worsened since baseline.

Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) and Events of Special Interest

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. AESIs were significant AEs that were judged to be of special interest because of clinical importance, known or suspected class effects, or based on nonclinical signals. Adverse events of special interest were cataplexy, sleep paralysis, complex, and sleep-related behaviors (parasomnias).

Percentage of Participants With Abnormalities in Vital Sign Parameters

Percentage of participants with abnormalities in vital sign parameters (pulse, supine and standing blood pressure [systolic and diastolic], body temperature, and body weight) were reported. Abnormally low values for parameters included pulse (beats per minute)- decrease value from baseline (>=) 15 to <=50; Systolic Blood Pressure (BP) (mmHg [Millimeter of mercury])- decrease value from baseline >=20 to <=90; Diastolic BP- decrease value from baseline >=15 to <=50; weight (Kilogram[Kg])- decrease from baseline of >=7%; Body temperature (Celsius [C])- <35.5. Abnormally high values for parameters included pulse- increase value from baseline >=15 to >=100; Systolic BP(mmHg)- increase from baseline of >=20 to >=180; Diastolic BP- increase value from baseline >=15 to >=105; weight(Kg)- increase from baseline of >=7%; body temperature (C)- >37.5.

Percentage of Participants With Abnormalities in Electrocardiogram (ECG) Parameters

Percentage of participants with abnormalities in ECG parameters were reported.

Percentage of Participants With Abnormalities in Clinical Laboratory Parameters

Percentage of participants with abnormalities in clinical laboratory parameters were reported.

Percentage of Participants With Sexual Dysfunction as Determined by Arizona Sexual Experiences Scale (ASEX) Total Score

Sexual dysfunction is defined as an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items. ASEX is a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each of the 5 items is rated on a 6-point Likert scale, ranging from 1 to 6. The 5 items are summed to create a total score, ranging from 5 to 30, with the higher scores indicating more sexual dysfunction.

Percentage of Participants With Clinically Relevant Changes in Extrapyramidal Symptoms Assessed by the Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) Score

The ESRS-A is an abbreviated manualized version of the ESRS, a semi-structured interview that rates parkinsonian symptoms, dystonia, dyskinesias, and akathisia over the previous 7 days. The ratings include a motor examination for rigidity, tremor, reduced facial expression or speech, impaired gait/posture, postural instability, and bradykinesia/hypokinesia. Twenty-four individual items are rated on a 6-point scale: 0=Absent, 1=Minimal, 2=Mild, 3=Moderate, 4=Severe, or 5=Extreme. Frequency is included as an index of severity.

Percentage of Participants With Suicidality Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) Score

C-SSRS is a clinician-rated instrument that reports severity and frequency of suicide-related ideation and behaviors. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (non-specific active suicidal thoughts), 3 (active suicidal ideation with any methods [not plan] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 6 (preparatory acts or behavior), 7 (aborted attempt), 8 (interrupted attempt), 9 (actual attempt [non-fatal]), and 10 (completed suicide [only applicable for post baseline]). Minimum total score 0, maximum total score 10; higher total scores indicate more suicidal ideation and/or suicidal behavior. If no events qualify for score of 1 to 10, score of 0 was assigned (0= "no event that can be assessed on the basis of C-SSRS"). Higher scores indicate greater severity.

Percentage of Participant With Potential Withdrawal Effects Assessed by the Physician Withdrawal Checklist (PWC)

Intensity of discontinuation symptoms was assessed (anxiety-nervousness, dysphoric mood/depression, Depersonalization-Derealization, , Diaphoresis, Diarrhea, Difficulty Concentrating, Remember, Dizziness-Lightheadedness, Fatigue-Lethargy-Lack of Energy, Headaches, Increased Acuity Sound Smell Touch, Irritability, Loss of Appetite, Muscle Aches or Stiffness, Nausea-Vomiting, Paresthesias, Poor Coordination, Restlessness-Agitation, Tremor-Tremulousness, Weakness), using the Physician Withdrawal Checklist (PWC-20) administered by a trained clinician/rater. Symptoms are rated on a scale of 0 (no symptom present), 1 (mild), 2 (moderate), and 3 (severe). Total scores range from 0 (no symptom) to 24 (severe symptom) calculated by adding the scores of following 8 items: Nausea-Vomiting, Diarrhea, Poor Coordination, Diaphoresis, Tremor-Tremulousness, Dizziness-Lightheadedness, Increased Acuity Sound Smell Touch, Paresthesias. Higher scores indicates more severe symptoms.

Change From Baseline in MADRS Total Score Over Time

Change From Baseline in MADRS Total Score Over Time, by Mode Dose

Change From Baseline in MADRS-6 Score Over Time

MADRS-6 is the depression subscale of the full MADRS, including the following 6 items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, pessimistic thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 36 which is calculated by adding the scores of all 6 items. Higher scores represent a more severe condition.

Full Information

NCT ID

NCT03321526

First Posted

October 23, 2017

Last Updated

May 1, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT03321526

Brief Title

A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy

Official Title

A 6-Month, Multicenter, Double-Blind, Randomized, Flexible-Dose, Parallel-Group Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Subjects With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

December 12, 2017 (Actual)

Primary Completion Date

June 13, 2019 (Actual)

Study Completion Date

June 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to assess the efficacy of flexibly dosed JNJ-42847922 (20 milligram [mg] or 40 mg) compared to flexibly dosed quetiapine extended-release (XR) (150 mg or 300 mg) as adjunctive therapy to an antidepressant drug in delaying time to all-cause discontinuation of study drug over a 6-months (24 weeks) treatment period, 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Depressive Disorder, Major

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

107 (Actual)

8. Arms, Groups, and Interventions

Arm Title

JNJ-42847922

Arm Type

Experimental

Arm Description

Arm Title

Quetiapine Extended-Release (XR)

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

JNJ-42847922

Other Intervention Name(s)

MIN-202;, Seltorexant

Intervention Description

Participants will receive JNJ-42847922 capsule orally.

Intervention Type

Drug

Intervention Name(s)

Placebo Matching to JNJ-42847922

Intervention Description

Participants will receive placebo capsule matching to JNJ-42847922 orally.

Intervention Type

Drug

Intervention Name(s)

Quetiapine XR

Intervention Description

Participants will receive quetiapine XR capsule orally.

Intervention Type

Drug

Intervention Name(s)

Placebo Matching to Quetiapine XR

Intervention Description

Participants will receive placebo capsule matching to quetiapine XR orally.

Intervention Type

Drug

Intervention Name(s)

Selective Serotonin Reuptake Inhibitor (SSRI)

Intervention Description

Participants will receive SSRI antidepressant (such as, citalopram, escitalopram, fluvoxamine, fluoxetine, paroxetine, sertraline, vilazodone or vortioxetine) as a part of background therapy (at the same dose, without change, every day and at approximately the same time as prior to entering the study) throughout the screening, double-blind, and follow-up phases (approximately up to Week 26).

Intervention Type

Drug

Intervention Name(s)

Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Intervention Description

Participants will receive SNRI antidepressant (such as duloxetine, milnacipran, levomilnacipran, venlafaxine, desvenlafaxine) as a part of background therapy (at the same dose, without change, every day and at approximately the same time as prior to entering the study) throughout the screening, double-blind, and follow-up phases (approximately up to Week 26).

Primary Outcome Measure Information:

Title

Time to All-Cause Discontinuation of Study Drug

Description

Time Frame

Up to Week 24

Secondary Outcome Measure Information:

Title

Percentage of Participants With Sustained Remission up to Week 24

Description

Time Frame

Up to Week 24

Title

Percentage of Participants With Sustained Response up to Week 24

Description

Time Frame

Up to Week 24

Title

Description

Time Frame

Baseline and Week 12

Title

Change From Baseline in MADRS Total Score in Participants With Significant Insomnia (Baseline ISI Score >=15) Versus Those Without Significant Insomnia (Baseline ISI Score <15) at Week 18

Description

Time Frame

Baseline and Week 18

Title

Change From Baseline in MADRS Total Score in Participants With Significant Insomnia (Baseline ISIscore >=15) Versus Those Without Significant Insomnia (Baseline ISI Score 15) at Week 24

Description

Time Frame

Baseline and Week 24

Title

Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Weeks 12, 18, and 24

Description

Time Frame

Baseline, Weeks 12, 18, and 24

Title

Percentage of Participants With Weight Gain of >=7% of Baseline Body Weight at Week 24

Description

Percentage of participants with weight gain of >=7% of baseline body weight at Week 24 were reported.

Time Frame

At Week 24

Title

Percentage of Participants With Shifts in Triglycerides From Normal to High

Description

Percentage of participants with shifts in triglycerides from normal to high (<150 milligrams per deciliter [mg/dL] at baseline to >=200 mg/dL at any post-baseline assessment) were reported.

Time Frame

Up to Week 24

Title

Percentage of Participants With Shifts in Triglycerides From Borderline to High

Description

Percentage of participants with shifts in triglycerides from borderline to high (>=150 to <200 mg/dL at baseline to >=200 mg/dL at any post-baseline assessment) were reported.

Time Frame

Up to Week 24

Title

Percentage of Participants With Shifts in Triglycerides From Normal to Very High

Description

Percentage of participants with shifts in triglycerides from normal to very high (<150 mg/dL at baseline to >=500 mg/dL at any post-baseline assessment) were reported.

Time Frame

Up to Week 24

Title

Percentage of Participants With Shifts in Triglycerides From Borderline to Very High

Description

Percentage of participants with shifts in triglycerides from borderline to very high (>=150 mg/dL to <200 mg/dL at baseline to >=500 mg/dL at any post-baseline assessment) were reported.

Time Frame

Up to Week 24

Title

Percentage of Participants With Shifts in Triglycerides From High to Very High

Description

Percentage of participants with shifts in triglycerides from high to very high (>=200 mg/dL to <500 mg/dL at baseline to >=500 mg/dL at any post-baseline assessment) were reported.

Time Frame

Up to Week 24

Title

Percentage of Participants With Shifts in Fasting Blood Glucose From Normal to Borderline

Description

Percentage of participants with shifts in fasting blood glucose from normal to borderline (<100 mg/dL at baseline to between >=100 and <126 mg/dL at any post-baseline assessment) were reported.

Time Frame

Up to Week 24

Title

Percentage of Participants With Shifts in Fasting Blood Glucose From Borderline to High

Description

Percentage of participants with shifts in fasting blood glucose from borderline to high (>=100 to <126 mg/dL at baseline to >=126 mg/dL at any post-baseline assessment) were reported.

Time Frame

Up to Week 24

Title

Percentage of Participants With Shifts in Fasting Blood Glucose From Normal to High

Description

Percentage of participants with shifts in fasting blood glucose from normal to high (<100 mg/dL at baseline to >=126 mg/dL at any post-baseline assessment) were reported.

Time Frame

Up to Week 24

Title

Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale Score at Weeks 12 and 24

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Change From Baseline in the Patient Global Impression Severity (PGI-S) Scale Score at Weeks 12 and 24

Description

The PGI-S is a self-report scale to measure severity of illness (1=none, 2=mild, 3=moderate, 4=severe). Higher score indicates more illness severity. Negative change in score indicates improvement.

Time Frame

Baseline, Weeks 12 and 24

Title

Change From Baseline in Quality of Life in Depression Scale (QLDS) Score at Weeks 12 and 24

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Change From Baseline in Patient Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 8a at Weeks 12 and 24

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Change From Baseline in Patient Reported Outcomes Measurement Information System-Sleep Related Impairment (PROMIS-SRI) Short Form 8a at Weeks 12 and 24

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Score at Weeks 12 and 24

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Change From Baseline in Symbol Digit Modalities Test (SDMT) at Weeks 6, 12, and 24

Description

Time Frame

Baseline, Weeks 6, 12, and 24

Title

Change From Baseline in Trail Making Test - Part B (TMT-Part B) at Weeks 6, 12, and 24

Description

Time Frame

Baseline, Weeks 6, 12, and 24

Title

Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) at Weeks 6, 12, and 24

Description

Time Frame

Baseline, Weeks 6, 12, and 24

Title

Change From Baseline in Salivary Cortisol Levels as Measured at Home Upon Awakening and During the Evening at Weeks 6 and 24

Description

Change from baseline in salivary cortisol levels as measured upon awakening and at home during the evening at Weeks 6 and 24 were reported.

Time Frame

Baseline, Weeks 6 and 24

Title

Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

Up to 24 weeks

Title

Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) and Events of Special Interest

Description

Time Frame

Up to 24 weeks

Title

Percentage of Participants With Abnormalities in Vital Sign Parameters

Description

Time Frame

Up to 24 weeks

Title

Percentage of Participants With Abnormalities in Electrocardiogram (ECG) Parameters

Description

Percentage of participants with abnormalities in ECG parameters were reported.

Time Frame

Up to 24 weeks

Title

Percentage of Participants With Abnormalities in Clinical Laboratory Parameters

Description

Percentage of participants with abnormalities in clinical laboratory parameters were reported.

Time Frame

Up to 24 weeks

Title

Percentage of Participants With Sexual Dysfunction as Determined by Arizona Sexual Experiences Scale (ASEX) Total Score

Description

Time Frame

Up to Endpoint (Up to 24 weeks)

Title

Percentage of Participants With Clinically Relevant Changes in Extrapyramidal Symptoms Assessed by the Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) Score

Description

Time Frame

Up to Endpoint (Up to 24 weeks)

Title

Percentage of Participants With Suicidality Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) Score

Description

Time Frame

Up to Endpoint (Up to 24 weeks)

Title

Percentage of Participant With Potential Withdrawal Effects Assessed by the Physician Withdrawal Checklist (PWC)

Description

Time Frame

Up to 26 weeks

Title

Change From Baseline in MADRS Total Score Over Time

Description

Time Frame

Baseline, Weeks 2, 4, 6, 12, 18, 24

Title

Change From Baseline in MADRS Total Score Over Time, by Mode Dose

Description

Time Frame

Baseline, Weeks 2, 4, 6, 12, 18, 24, and 26

Title

Change From Baseline in MADRS-6 Score Over Time

Description

Time Frame

Baseline, Weeks 2, 4, 6, 12, 18, 24, and 26

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female of non-childbearing potential (WONCBP) outpatients, 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). 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 assessed 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, as specified in the MGH-ATRQ, for any particular antidepressant. The inadequate response must include the participant's current antidepressant treatment Be receiving monotherapy treatment for depressive symptoms with 1 of the following selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (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 participant 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 Have a Body Mass Index (BMI) between 18 and 35 kilogram per meter square (kg/m^2) inclusive (BMI equal to [=] weight/height^2) 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 there are abnormalities, they must be consistent with the underlying illness in the study population. If the results of the clinical laboratory tests are outside the normal reference ranges, the participant may 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: Have Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the hypothalamic-pituitary-adrenal (HPA) axis Have a history of epilepsy, neuroleptic malignant syndrome (NMS) or Tardive Dyskinesia Have a history of previous non-response to an adequate trial of quetiapine as an adjunctive treatment for MDD (adequate trial defined as >=150 mg for 4 weeks or more) and/or a history of lack of response to 3 or more adequate antidepressant treatments and/or a history or evidence of noncompliance with current antidepressant therapy Have taken a known moderate or strong inhibitor/inducer of cytochrome P450 (CYP)3A4 and CYP2C9 or a dual inhibitor/inducer of CYP3A4 and CYP2C9 within 14 days (or after washout that is, duration of 5 times the drug's half-life) before the first study drug administration on Day 1 until the follow-up visit. Fluvoxamine is a moderate CYP2C9 inhibitor and a mild CYP3A inhibitor, and will not be excluded from the study Have a history or current diagnosis of a psychotic disorder, bipolar disorder, intellectual disability, autism spectrum disorder, borderline personality disorder, somatoform disorders, or fibromyalgia

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

Facility Name

NoesisPharma Research

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85032

Country

United States

Facility Name

Clinical Research Consortium Arizona

City

Tempe

State/Province

Arizona

ZIP/Postal Code

85283

Country

United States

Facility Name

Woodland Research Northwest

City

Rogers

State/Province

Arkansas

ZIP/Postal Code

72758

Country

United States

Facility Name

Collaborative NeuroScience Network

City

Garden Grove

State/Province

California

ZIP/Postal Code

92845

Country

United States

Facility Name

Pacific Institute of Medical Sciences

City

Los Angeles

State/Province

California

ZIP/Postal Code

90024

Country

United States

Facility Name

National Research Institute

City

Los Angeles

State/Province

California

ZIP/Postal Code

90057

Country

United States

Facility Name

Excell Research Inc

City

Oceanside

State/Province

California

ZIP/Postal Code

92056

Country

United States

Facility Name

Desert Valley Research

City

Rancho Mirage

State/Province

California

ZIP/Postal Code

92270

Country

United States

Facility Name

Anderson Clinical Research

City

Redlands

State/Province

California

ZIP/Postal Code

92374

Country

United States

Facility Name

Artemis Institute for Clinical Research

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

Syrentis Clinical Research

City

Santa Ana

State/Province

California

ZIP/Postal Code

92705

Country

United States

Facility Name

Research Center for Clinical Studies, Inc.

City

Norwalk

State/Province

Connecticut

ZIP/Postal Code

06851

Country

United States

Facility Name

Clinical Research of South Florida

City

Coral Gables

State/Province

Florida

ZIP/Postal Code

33134

Country

United States

Facility Name

SIH Research

City

Kissimmee

State/Province

Florida

ZIP/Postal Code

34759

Country

United States

Facility Name

Premier Clinical Research

City

Miami

State/Province

Florida

ZIP/Postal Code

33122

Country

United States

Facility Name

Innova Clinical Trials

City

Miami

State/Province

Florida

ZIP/Postal Code

33133

Country

United States

Facility Name

Arocha Research Center Inc

City

Miami

State/Province

Florida

ZIP/Postal Code

33145

Country

United States

Facility Name

Suncoast Clinical Research

City

New Port Richey

State/Province

Florida

ZIP/Postal Code

34652

Country

United States

Facility Name

Stedman Clinical Trials

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

Facility Name

Northwest Behavioral Research Center

City

Marietta

State/Province

Georgia

ZIP/Postal Code

30060

Country

United States

Facility Name

Suburban Clinical Research Group, Inc

City

Bolingbrook

State/Province

Illinois

ZIP/Postal Code

60490

Country

United States

Facility Name

RxClinicals

City

Crystal Lake

State/Province

Illinois

ZIP/Postal Code

60012

Country

United States

Facility Name

Alexian Brothers Health System

City

Hoffman Estates

State/Province

Illinois

ZIP/Postal Code

60169

Country

United States

Facility Name

Psychiatric Medicine Associates LLC

City

Skokie

State/Province

Illinois

ZIP/Postal Code

60076

Country

United States

Facility Name

American Research, LLC

City

Jeffersonville

State/Province

Indiana

ZIP/Postal Code

47130

Country

United States

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

Phoenix Medical Research, Inc.

City

Prairie Village

State/Province

Kansas

ZIP/Postal Code

66208

Country

United States

Facility Name

Johns Hopkins University School of Medicine

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21218

Country

United States

Facility Name

BTC of New Bedford

City

New Bedford

State/Province

Massachusetts

ZIP/Postal Code

02740

Country

United States

Facility Name

Boston Clinical Trials & Medical Research

City

Roslindale

State/Province

Massachusetts

ZIP/Postal Code

02135

Country

United States

Facility Name

Rochester Center for Behavioral Medicine (RCBM)

City

Rochester Hills

State/Province

Michigan

ZIP/Postal Code

48307

Country

United States

Facility Name

Midwest Research Group

City

Saint Charles

State/Province

Missouri

ZIP/Postal Code

63304

Country

United States

Facility Name

PsychCare Consultants Research

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63128

Country

United States

Facility Name

Clinical Research Consortium

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89119-5190

Country

United States

Facility Name

SPRI Clinical Trials, LLC

City

Brooklyn

State/Province

New York

ZIP/Postal Code

11235

Country

United States

Facility Name

CNS Research Science, Inc.

City

Jamaica

State/Province

New York

ZIP/Postal Code

11432

Country

United States

Facility Name

Hapworth Psychiatric Medical PLLC

City

New York

State/Province

New York

ZIP/Postal Code

10019

Country

United States

Facility Name

Carolina Partners c/o Tripha Life Sciences

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27606

Country

United States

Facility Name

Patient Priority Clinical Sites, LLC

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45215

Country

United States

Facility Name

Intend Research

City

Norman

State/Province

Oklahoma

ZIP/Postal Code

73069

Country

United States

Facility Name

IPS Research Company

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73103

Country

United States

Facility Name

Sooner Clinical Research

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73112

Country

United States

Facility Name

BTC Network

City

Lincoln

State/Province

Rhode Island

ZIP/Postal Code

02865

Country

United States

Facility Name

Hawkins Psychiatry, PC

City

Arlington

State/Province

Texas

ZIP/Postal Code

76013

Country

United States

Facility Name

Baylor College of Medicine

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Houston Endoscopy and Research Center, Inc.

City

Houston

State/Province

Texas

ZIP/Postal Code

77079

Country

United States

Facility Name

Texas Center for Drug Development, Inc

City

Houston

State/Province

Texas

ZIP/Postal Code

77081

Country

United States

Facility Name

Pillar Clinical Research, LLC

City

Richardson

State/Province

Texas

ZIP/Postal Code

75080

Country

United States

Facility Name

Ericksen Research and Development

City

Clinton

State/Province

Utah

ZIP/Postal Code

84015

Country

United States

Facility Name

Northwest Clinical Research Center

City

Bellevue

State/Province

Washington

ZIP/Postal Code

98004

Country

United States

12. IPD Sharing Statement

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A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy

Depressive Disorder, Major

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial