Clinical trial NCT03321526: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-10-25
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the 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).


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

Primary outcomes:
measure: Time to All-Cause Discontinuation of Study Drug
timeFrame: Up to Week 24
Secondary outcomes:
measure: Percentage of Participants With Sustained Remission up to Week 24
timeFrame: Up to Week 24
measure: Percentage of Participants With Sustained Response up to Week 24
timeFrame: Up to Week 24
measure: 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
timeFrame: Baseline and Week 12
measure: 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
timeFrame: Baseline and Week 18
measure: 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
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Weeks 12, 18, and 24
timeFrame: Baseline, Weeks 12, 18, and 24
measure: Percentage of Participants With Weight Gain of >=7% of Baseline Body Weight at Week 24
timeFrame: At Week 24
measure: Percentage of Participants With Shifts in Triglycerides From Normal to High
timeFrame: Up to Week 24
measure: Percentage of Participants With Shifts in Triglycerides From Borderline to High
timeFrame: Up to Week 24
measure: Percentage of Participants With Shifts in Triglycerides From Normal to Very High
timeFrame: Up to Week 24
measure: Percentage of Participants With Shifts in Triglycerides From Borderline to Very High
timeFrame: Up to Week 24
measure: Percentage of Participants With Shifts in Triglycerides From High to Very High
timeFrame: Up to Week 24
measure: Percentage of Participants With Shifts in Fasting Blood Glucose From Normal to Borderline
timeFrame: Up to Week 24
measure: Percentage of Participants With Shifts in Fasting Blood Glucose From Borderline to High
timeFrame: Up to Week 24
measure: Percentage of Participants With Shifts in Fasting Blood Glucose From Normal to High
timeFrame: Up to Week 24
measure: Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale Score at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in the Patient Global Impression Severity (PGI-S) Scale Score at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Quality of Life in Depression Scale (QLDS) Score at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Patient Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 8a at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Patient Reported Outcomes Measurement Information System-Sleep Related Impairment (PROMIS-SRI) Short Form 8a at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Score at Weeks 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Symbol Digit Modalities Test (SDMT) at Weeks 6, 12, and 24
timeFrame: Baseline, Weeks 6, 12, and 24
measure: Change From Baseline in Trail Making Test - Part B (TMT-Part B) at Weeks 6, 12, and 24
timeFrame: Baseline, Weeks 6, 12, and 24
measure: Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) at Weeks 6, 12, and 24
timeFrame: Baseline, Weeks 6, 12, and 24
measure: Change From Baseline in Salivary Cortisol Levels as Measured at Home Upon Awakening and During the Evening at Weeks 6 and 24
timeFrame: Baseline, Weeks 6 and 24
measure: Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 24 weeks
measure: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) and Events of Special Interest
timeFrame: Up to 24 weeks
measure: Percentage of Participants With Abnormalities in Vital Sign Parameters
timeFrame: Up to 24 weeks
measure: Percentage of Participants With Abnormalities in Electrocardiogram (ECG) Parameters
timeFrame: Up to 24 weeks
measure: Percentage of Participants With Abnormalities in Clinical Laboratory Parameters
timeFrame: Up to 24 weeks
measure: Percentage of Participants With Sexual Dysfunction as Determined by Arizona Sexual Experiences Scale (ASEX) Total Score
timeFrame: Up to Endpoint (Up to 24 weeks)
measure: Percentage of Participants With Clinically Relevant Changes in Extrapyramidal Symptoms Assessed by the Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) Score
timeFrame: Up to Endpoint (Up to 24 weeks)
measure: Percentage of Participants With Suicidality Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Up to Endpoint (Up to 24 weeks)
measure: Percentage of Participant With Potential Withdrawal Effects Assessed by the Physician Withdrawal Checklist (PWC)
timeFrame: Up to 26 weeks
measure: Change From Baseline in MADRS Total Score Over Time
timeFrame: Baseline, Weeks 2, 4, 6, 12, 18, 24
measure: Change From Baseline in MADRS Total Score Over Time, by Mode Dose
timeFrame: Baseline, Weeks 2, 4, 6, 12, 18, 24, and 26
measure: Change From Baseline in MADRS-6 Score Over Time
timeFrame: Baseline, Weeks 2, 4, 6, 12, 18, 24, and 26
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: NoesisPharma Research
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortium Arizona
state: Arizona
city: Rogers
country: United States
facility: Woodland Research Northwest
state: Arkansas
city: Garden Grove
country: United States
facility: Collaborative NeuroScience Network
state: California
city: Los Angeles
country: United States
facility: Pacific Institute of Medical Sciences
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Oceanside
country: United States
facility: Excell Research Inc
state: California
city: Rancho Mirage
country: United States
facility: Desert Valley Research
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Norwalk
country: United States
facility: Research Center for Clinical Studies, Inc.
state: Connecticut
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Kissimmee
country: United States
facility: SIH Research
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research
state: Florida
city: Miami
country: United States
facility: Innova Clinical Trials
state: Florida
city: Miami
country: United States
facility: Arocha Research Center Inc
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Marietta
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Bolingbrook
country: United States
facility: Suburban Clinical Research Group, Inc
state: Illinois
city: Crystal Lake
country: United States
facility: RxClinicals
state: Illinois
city: Hoffman Estates
country: United States
facility: Alexian Brothers Health System
state: Illinois
city: Skokie
country: United States
facility: Psychiatric Medicine Associates LLC
state: Illinois
city: Jeffersonville
country: United States
facility: American Research, LLC
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Prairie Village
country: United States
facility: Phoenix Medical Research, Inc.
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: New Bedford
country: United States
facility: BTC of New Bedford
state: Massachusetts
city: Roslindale
country: United States
facility: Boston Clinical Trials & Medical Research
state: Massachusetts
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine (RCBM)
state: Michigan
city: Saint Charles
country: United States
facility: Midwest Research Group
state: Missouri
city: Saint Louis
country: United States
facility: PsychCare Consultants Research
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Consortium
state: Nevada
city: Brooklyn
country: United States
facility: SPRI Clinical Trials, LLC
state: New York
city: Jamaica
country: United States
facility: CNS Research Science, Inc.
state: New York
city: New York
country: United States
facility: Hapworth Psychiatric Medical PLLC
state: New York
city: Raleigh
country: United States
facility: Carolina Partners c/o Tripha Life Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Patient Priority Clinical Sites LLC
state: Ohio
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma City
country: United States
facility: Sooner Clinical Research
state: Oklahoma
city: Lincoln
country: United States
facility: BTC Network
state: Rhode Island
city: Arlington
country: United States
facility: Hawkins Psychiatry, PC
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Endoscopy and Research Center, Inc.
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development Inc
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Clinton
country: United States
facility: Ericksen Research and Development
state: Utah
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: