Clinical trial NCT03374475: A Study to Investigate the Antidepressant Mechanism-of-action of JNJ-42847922 in Participants With Major Depressive Disorder
Official title: An Exploratory, Multicenter, Placebo-controlled, Randomized, Double-blind Study to Investigate the Antidepressant Mechanism-of-action of JNJ-42847922 in Subjects With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Depressive Disorder, Major
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-12-15
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Total Score
timeFrame: Baseline up to Day 57
measure: Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Sleep Item-Adjusted Total Score
timeFrame: Baseline up to Day 57
measure: Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Anxiety/Somatization Factor Score
timeFrame: Baseline up to Day 57
measure: Change From Baseline in 6 Item Subscale From HDRS17 (HAM-D6) Score
timeFrame: Baseline up to Day 57
Secondary outcomes:
measure: Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16)
timeFrame: Baseline up to Day 67
measure: Association Between Major Depressive Disorder (MDD) Symptoms and Signals of Hyper-Arousal
timeFrame: Baseline up to Day 67
measure: Performance Score on a Cognitive Test Battery Evaluated by Symbol Digit Matching Test (SDMaT)
timeFrame: Baseline
measure: Performance Score on a Cognitive Test Battery Evaluated by Word List Recall Test (WLRT)
timeFrame: Baseline
measure: Performance Score on a Cognitive Test Battery Evaluated by Trail Making Test Form B (TMT-B)
timeFrame: Baseline
measure: Change From Baseline in Bond & Lader (B&L) Visual Analogue Scale (VAS)
timeFrame: Baseline up to Day 57
measure: Change From Baseline in Profile of Mood States (POMS)
timeFrame: Baseline up to Day 57
measure: Plasma Concentration of JNJ- 42847922 and its Metabolites
timeFrame: Day 36 to 40 (over 48 hours during Visit 6)
measure: Percent Change From Baseline in Biomarker Levels
timeFrame: Day 36 to 40 (over 48 hours during Visit 6)
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to end of the study (Day 67)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Marcos
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
city: Mechelen
country: Belgium
facility: SGS Phase 1 Unit AZ St-Maarten
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
city: Berlin
country: Germany
facility: Charite Research Organisation GmbH
city: Berlin
country: Germany
facility: Emovis GmbH
city: Hannover
country: Germany
facility: Fraunhofer-Institut für Toxikologie und Experimentelle Medizin
city: Schwerin
country: Germany
facility: Somni Bene GmbH
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
city: Blackpool
country: United Kingdom
facility: MAC Clinical Research
city: Liverpool
country: United Kingdom
facility: MAC Clinical Research
city: London
country: United Kingdom
facility: Hammersmith Medicines Research
city: Manchester
country: United Kingdom
facility: MAC Clinical Research
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: