Clinical trial NCT02902601: A Study to Investigate the Safety, Tolerability, and Pharmacodynamics of JNJ-54175446 in Participants With Major Depressive Disorder
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Safety, Tolerability, and Pharmacodynamics of JNJ-54175446 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: 2016-09-16
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to investigate the safety and tolerability of JNJ 54175446 in participants with Major Depressive Disorder (MDD).


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) must be between 18 and 32 kilogram per square meter (kg/m\^2) inclusive
* Related to symptoms of depression: Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or V diagnostic criteria for Major Depressive Disorder \[MDD\] (International Classification of Diseases (ICD)-code F32.x and F33.x), without psychotic features, as confirmed by the MINI 6.0; participant must have an IDS-C30 total score greater than or equal to (\>=) 30 using the semi-structured interview guide for the IDS-C30
* Participant is, during this episode of depression, treatment naïve OR treated with at most one Selective serotonin reuptake inhibitor (SSRI) over a minimum of 6 weeks and a maximum of 6 months, and subject is being treated at an adequate dose, showing a partial response at enrolment
* A woman of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test upon admission
* 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 a primary DSM-IV or V diagnosis of general anxiety disorder (GAD), panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, anorexia nervosa, or bulimia nervosa. Participants with comorbid GAD, social anxiety disorder, or panic disorder for whom MDD is considered the primary diagnosis are not excluded
* Has a length of current major depressive episode greater than (\>) 24 months despite adequate treatment
* Has failed more than 2 treatments with a different pharmacological mode of action despite an adequate dose and duration during a previous, or the current depressive episode
* Participant has a history of substance use disorder according to DSM-V criteria, except nicotine or caffeine, within 6 months before Screening. However, participants who have completed a treatment for (alcohol) addiction more than 8 weeks prior to first dose administration and are under continuous control of the study center, may be included if the risk to fall back is considered minimal and no significant abnormalities are shown in clinical laboratory or other predose safety assessments
* Obstructive sleep apnea/hypopnea (apnea/hypopnea index \>10) or restless legs syndrome (periodic leg movements with arousal index \>15) as assessed on the first or second polysomnography (PSG) recording during screening

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to Day 17
Secondary outcomes:
measure: Effect of JNJ-54175446 Versus Placebo on Total Sleep Deprivation (TSD)-Induced Changes in Depressive Symptoms by HDRS17/IDS-C30 Rating Scale
timeFrame: Baseline, Day 4 and 10: 2 to 8 hours post dose, Day 17
measure: Effect of JNJ-54175446 Versus Placebo on Total Sleep Deprivation (TSD)-Induced Changes in Depressive Symptoms by QIDS-SR16/QIDS-SR10 Rating Scale
timeFrame: Baseline, Day 3 and 10: 2 to 8 hours post dose, Day 17
measure: Effect of JNJ-54175446 Versus Placebo on TSD-Induced Changes in Biomarker Profiles (interleukin [IL]-1 beta, cortisol)
timeFrame: Day 1 and 4: Predose, 2, 8 hours postdose, Day 10: Predose
measure: Effect of JNJ-54175446 Versus Placebo on Latency to Persistent Sleep (LPS)
timeFrame: Baseline, Day 2 to 3 and Day 4 to 5
measure: Effect of JNJ-54175446 Versus Placebo on Total Sleep Time (TST)
timeFrame: Baseline, Day 2 to 3 and Day 4 to 5
measure: Effect of JNJ-54175446 Versus Placebo on Wake After Sleep Onset (WASO)
timeFrame: Baseline, Day 2 to 3 and Day 4 to 5
measure: Effect of JNJ-54175446 Versus Placebo on Sleep Efficiency (SE)
timeFrame: Baseline, Day 2 to 3 and Day 4 to 5
measure: Effect of JNJ-54175446 Versus Placebo on Snaith-Hamilton Pleasure Scale [SHAPS])
timeFrame: Baseline, Day 3, 4, 5 and 10: 2 to 8 hours postdose
measure: Effect of JNJ-54175446 Versus Placebo on Profile of Mood States brief form (POMS)
timeFrame: Baseline, Day 3, 10: 2 to 8 hours postdose, Day 4, 5: 2 to 8 and 19 hours postdose
measure: Effect of JNJ-54175446 Versus Placebo on Emotional Faces Recognition Test
timeFrame: Baseline, Day 4 and 10: 2 to 8 hours postdose
measure: Effect of JNJ-54175446 Versus Placebo on Soluble Biomarkers (Inclusive Ex-vivo Lipopolysaccharide [LPS]/Benzoylated(Bz) Adenosine Triphosphate [ATP]-Induced IL-1 Beta Release)
timeFrame: Day 1 and 4: Predose, 2, 8 hours postdose, Day 10: Predose
measure: Effect of JNJ-54175446 Versus Placebo on Central Pharmacodynamic (PD) by Motor Learning by Adaptive Tracking Test
timeFrame: Baseline, Day 10: Predose, 1, 2, 4 and 6 hour post dose
measure: Effect of JNJ-54175446 Versus Placebo on Sustained Attention by the Three Choice Vigilance Task (3CVT) With EEG
timeFrame: Baseline, Day 3, 4, 5 and 10: 2 to 8 hours postdose
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Minimum Observed Plasma Concentration (Cmin) of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Trough Plasma Concentration (Ctrough) of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Average Plasma Concentration at Steady State (Cavg) of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Area Under the Plasma ConcentrationTime Curve During a Dosing Interval (tau) [AUCtau] of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Area Under the Plasma ConcentrationTime Curve From Time Zero to Time 't' (AUC[0t]) of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Apparent Elimination HalfLife (t1/2) of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Ratio of the Maximum Plasma Concentration (Peak) to Trough Observed Concentration of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Accumulation Ratio Based on AUC of JNJ-54175446
timeFrame: Day 1: Predose, 1, 2, 4, 8, 10 hour postdose; Day 2 and 3: Predose; Day 4: Predose, 2, 4, 8 hour postdose; Day 5 and 7: Predose; Day 10: Predose, 1, 2, 4, 8, 10, 24, 48 hour postdose; Day 17
measure: Effect of JNJ-54175446 Versus Placebo on a Reward Test
timeFrame: Baseline, Day 3, 4, 5 and 10: 2 to 8 hours postdose
Other outcomes:
Locations:
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Schwerin
country: Germany
city: Leiden
country: Netherlands
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: