Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
JNJ-42847922 · 16 trials · 7 indications
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.
Change in LPS was measured on Night 1 by PSG. LPS is the time in minutes from 'lights out' that marks the starting of total recording time to the first epoch recorded as sleep. The LPS change from baseline on Night 1 was calculated as (LPS at Night 1 minus Baseline LPS). Negative changes in LPS indicated improvement.
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.
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 were events between the initial administration of study drug and 2 days after the last administration of study drug.
Percentage of participants with clinically significant laboratory abnormalities were reported which included Gamma-glutamyl transferase (GGT), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Albumin , bicarbonate, bilirubin, calcium, chloride, cholesterol, creatinine, direct bilirubin, glucose, high density lipoprotein (HDL) cholesterol, hemoglobin A1C, low density lipoprotein (LDL) cholesterol, phosphate, potassium, protein, sodium, triglycerides, urate, and urea nitrogen.
Change from baseline in vital signs (SBP and DBP) at Day 8 was reported.
Change from baseline in vital signs (SBP and DBP) at Day 22 was reported.
Change from baseline in vital signs (SBP and DBP) at Day 42 was reported.
Change from baseline in vital signs (SBP and DBP) at endpoint was reported.
Change from baseline in vital sign (PR) at Day 8 was reported.
Change from baseline in vital sign (PR) at Day 22 was reported.
Change from baseline in vital sign (PR) at Day 42 was reported.
Change from baseline in vital sign (PR) at endpoint (Week 6) was reported.
Change from baseline in vital Sign (temperature) at Day 8 was reported.
Change from baseline in vital Sign (temperature) at Day 22 was reported.
Change from baseline in vital Sign (temperature) at Day 42 was reported.
Change from baseline in vital Sign (temperature) at endpoint (Week 6) was reported.
Change from baseline in physical examination (waist circumference) was reported.
Change from baseline in physical examination (body weight) was reported.
Change from baseline in physical examination (BMI) was reported.
Percentage of participants with treatment-emergent abnormal ECG values (Heart rate less than or equal to \[\<=\] 50 or greater than or equal to \[\>=\] 100 beats per minute \[bpm\], PR interval \<=120 or \>=200 milliseconds \[msec\], QRS interval \<=60 or \>=120 msec, and QT interval \<=200 or \>=500 msec) outside pre-defined limits were reported.
C-SSRS is a clinician-rated instrument that reports severity of both suicidal ideation and behavior. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific 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: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. Minimum total score 0, maximum total score 5; 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.
Effect on sexual functioning was assessed using the ASEX score. The 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 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.
Intensity of discontinuation symptoms was assessed (for example: underlying depression; anxiety-nervousness; dysphoric mood/depression; difficulty concentrating; weakness; fatigue-lethargy-lack of energy; irritability), using the Physician Withdrawal Checklist (PWC-20) administered by a trained clinician/rater. Symptoms are rated on a scale 0 (No symptom present) and 3 (severe symptoms). Total scores range from 0 to 24 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 indicating more severe symptoms.
Intensity of discontinuation symptoms was assessed (for example: underlying depression; anxiety-nervousness; dysphoric mood/depression; difficulty concentrating; weakness; fatigue-lethargy-lack of energy; irritability), using the Physician Withdrawal Checklist (PWC-20) administered by a trained clinician/rater. Symptoms are rated on a scale 0 (No symptom present) and 3 (severe symptoms). Total scores range from 0 to 24 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 indicating more severe symptoms.
The total sleep time divided by the total time in bed (that is, the number of minutes from the beginning of the Polysomnography recording to the end of the recording).
Cmax is defined as maximum observed plasma analyte concentration of JNJ-42847922 and its metabolites M12 and M16.
AUC(0-last) is defined as area under the plasma analyte concentration versus time curve from time zero to time of last measurable concentration of JNJ-42847922 and its metabolites M12 and M16.
AUC(0-infinity) is defined as the area under the plasma analyte concentration versus time curve from time zero to infinite time of JNJ-42847922 and its metabolites M12 and M16.
Cmax is defined as maximum observed plasma analyte concentration of JNJ-42847922 and its metabolites A and B.
AUC(0-Last) is defined as area under the plasma analyte concentration versus time curve from time 0 to time of last measurable concentration of JNJ-42847922 and its metabolites A and B.
AUC(0-infinity) is defined as the area under the plasma analyte concentration versus time curve from time 0 to infinite time of JNJ-42847922 and its metabolites A and B.
The HDRS17 is a Clinician-Administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a total score range of 0 to 52. It is the most widely used symptom severity measure for depression. Each of the 17 items is rated by the clinician on either a 3- point (0 to 2) or a 5-point scale (0 to 4). The point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Total score will be calculated by summing up the individual item score. The higher the score, the more severe the depression.
The HDRS17 is a Clinician-Administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. It is the most widely used symptom severity measure for depression. Each of the 17 items is rated by the clinician on either a 3- point (0 to 2) or a 5-point scale (0 to 4). The point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. HDRS17 Sleep Item-Adjusted is derived from the HDRS17 scale excluding the 3 sleep items (4, 5, and 6) from the total score.
The HDRS17 anxiety/somatization factor derived from Cleary and Guy's factor analysis of the HDRS scale, includes six items from the original 17-item version: the items for psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Anxious depression is often defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, as reflected in an anxiety/ somatization factor score greater than or equal to (\>=) 7. The score ranges from 0 to 18, with higher scores indicating greater severity of symptoms.
The 6-Item Hamilton Depression Scale (HAMD-6), derived by the sum of HAMD-17 items (the six items in the HAM-D6 are: depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and general somatics \[tiredness and pains\]), evaluates "core" symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe). The higher the score, the more severe the depression.
Blood samples will be collected after dosing of JNJ-42847922 on each occasion to assess the pharmacokinetics of JNJ-42847922 and metabolites M12, M16 with and without rifampin.
Blood samples will be collected after dosing of JNJ-42847922 on each occasion to assess the pharmacokinetics of JNJ-42847922 and metabolites M12, M16 with and without rifampin.
Blood samples will be collected after dosing of JNJ-42847922 on each occasion to assess the pharmacokinetics of JNJ-42847922 and metabolites M12, M16 with and without rifampin.
Blood samples will be collected after dosing of JNJ-42847922 on each occasion to assess the pharmacokinetics of JNJ-42847922 and metabolites M12, M16 with and without rifampin.
Blood samples will be collected after dosing of JNJ-42847922 on each occasion to assess the pharmacokinetics of JNJ-42847922 and metabolites M12, M16 with and without rifampin.
Blood samples will be collected after dosing of JNJ-42847922 on each occasion to assess the pharmacokinetics of JNJ-42847922 and metabolites M12, M16 with and without rifampin.
The SDLP will be measured from a simulated road tracking test over about 15 minutes. Instructed speed is 100 kilometer (km)/hour.
The Cmax is the maximum observed plasma concentration of Midazolam.
The Cmax is the maximum observed plasma concentration of 1-Hydroxymidazolam.
The Cmax is the maximum observed plasma concentration of Warfarin.
The Tmax is the time to reach the maximum observed plasma concentration of Midazolam.
The Tmax is the time to reach the maximum observed plasma concentration of 1-Hydroxymidazolam.
The Tmax is the time to reach the maximum observed plasma concentration of Warfarin.
Time to last measurable plasma concentration is evaluated.
Time to last measurable plasma concentration is evaluated.
Time to last measurable plasma concentration is evaluated.
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.
The AUC (0-infinity) is the area under the plasma Midazolam concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma Midazolam concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
The AUC (0-infinity) is the area under the plasma 1-Hydroxymidazolam concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma 1-Hydroxymidazolam concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
The AUC (0-infinity) is the area under the plasma Warfarin concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma Warfarin concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
The CL/F is defined as Dose/AUC (0-infinity).
The CL/F is defined as Dose/AUC (0-infinity).
The CL/F is defined as Dose/AUC (0-infinity).
The Vd/F is defined as Dose/\[Lambda (z)\*AUC (0-infinity)\].
The Vd/F is defined as Dose/\[Lambda (z)\*AUC (0-infinity)\].
The Vd/F is defined as Dose/\[Lambda (z)\*AUC (0-infinity)\].
The Emax for prothrombin time (PT) will be assessed.
The Emax for activated partial thromboplastin time (aPTT) will be assessed.
The Emax for international normalized ratio (INR) will be assessed.
The Tmax is the time to reach the maximum observed plasma concentration of JNJ-42847922.
The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.
The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.
The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration of JNJ-42847922 will be reported.
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
The Cmax is the maximum observed plasma concentration.
The Cmax is the maximum plasma concentration.
The tmax is time to reach the maximum observed plasma concentration.
The tmax is time to last observed quantifiable plasma concentration.
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.
The AUC (0-24) is the area under the plasma concentration-time curve from time 0 to time 24 hours
Elimination half-life (t \[1/2\] Lambda) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).
Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Clearance is a quantitative measure of the rate at which a drug substance is removed from the body. The CL/F will be calculated by dividing the dose by AUC (0-infinity)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.The Vd(z)/F will be calculated by dividing CL/F by lambda(z).
Mean residence time, calculated as area under the first moment curve (AUMC\[0-infinity\]/AUC(0-infinity).
amount excreted into the urine, calculated by multiplying the urinary volume with the urinary concentration.
Amount excreted into the urine, expressed as a percentage of the administered dose, calculated as \[Ae/dose\]\*100, and corrected for molecular weight when necessary.
Renal clearance calculated as Ae (total)/AUC (infinity).
BP is the pressure of the blood within the arteries. It is produced primarily by the contraction of the heart muscle. BP measurement is recorded by 2 numbers: systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles).
Laboratory values included Hematology, clinical chemistry and urinalysis.
Physical and neurological examination will be performed.
LPS is with lights off, appearance of first epoch of Stage 1 (light sleep), Stage 2 (light sleep), Stage 3 (deep sleep), and Stage 4 (rapid eye movement sleep) sleep followed by at least 20 consecutive epochs without any Stage 0 sleep (awake but sleepy). LPS will be accessed on Day 1 of each treatment period (Periods 1, 2, 3, and 4).
| Arm | Type | Description |
|---|---|---|
| JNJ-42847922 | EXPERIMENTAL | 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. |
| Quetiapine Extended-Release (XR) | ACTIVE_COMPARATOR | 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. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive matching placebo to JNJ-42847922 as oral capsules at normal study bedtime on Nights 1 through 14. |
| JNJ-42847922 5 milligram (mg) | EXPERIMENTAL | Participant will receive JNJ-42847922 5 mg dose as oral capsules at normal study bedtime on Nights 1 through 14. |
| JNJ-42847922 10 mg plus Placebo | EXPERIMENTAL | Participant will receive JNJ-42847922 10 mg as oral capsule and one placebo capsule at normal study bedtime on Nights 1 through 14. |
| JNJ-42847922 20 mg plus Placebo | EXPERIMENTAL | Participant will receive JNJ-42847922 20 mg as oral capsule and one placebo capsule at normal study bedtime on Nights 1 through 14. |
| Zolpidem plus Placebo | EXPERIMENTAL | Participants will receive Zolpidem 5 mg plus one placebo capsule or 10 mg dose as oral capsule at normal study bedtime on Nights 1 through 14. |
| JNJ-42847922 then Placebo | EXPERIMENTAL | Participants receive 2\*20 milligram (mg) tablet of JNJ-42847922 orally once daily from Day 1 to Day 5 of period 1. After a washout period of 5 to 9 days participants will receive matching placebo from Day 1 to Day 5 of period 2. |
| Placebo then JNJ-42847922 | EXPERIMENTAL | Participants will receive matching placebo from Day 1 to Day 5 of period 1. After a washout period of 5 to 9 days participants will receive 2\*20 mg tablet of JNJ-42847922 orally once daily from Day 1 to Day 5 of period 2. |
| Part 1: Cohort 1 (JNJ-42847922) | EXPERIMENTAL | Participants with normal hepatic function will receive Dose 1 of JNJ-42847922 on Day 1. |
| Part 1: Cohort 2 (JNJ-42847922) | EXPERIMENTAL | Participants with mild hepatic impairment will receive Dose 1 of JNJ-42847922 on Day 1. |
| Part 1: Cohort 3 (JNJ-42847922) | EXPERIMENTAL | Participants with moderate hepatic impairment will receive Dose 2 of JNJ-42847922 on Day 1. |
| Part 2: Cohort 4 (Optional) (JNJ-42847922) | EXPERIMENTAL | Participants with moderate hepatic impairment will receive Dose 1 (depending on the results of Cohort 3) of JNJ-42847922 on Day 1. |
| Part 2: Cohort 5 (Optional) (JNJ-42847922) | EXPERIMENTAL | Participants with severe hepatic impairment will receive Dose 2 or Dose 3 (depending on the results of Part 1) of JNJ-42847922 on Day 1. |
| Parts 1 and 2: Cohort 1 (JNJ-42847922) | ACTIVE_COMPARATOR | Healthy participants with normal renal function \[estimated glomerular filtration rate (eGFR) greater than or equal to (\>=) 90 milliliter (mL)/minute (min)\] will receive single oral dose of JNJ-42847922 on Day 1. |
| Part 2 (Optional): Cohort 3 (JNJ-42847922) | EXPERIMENTAL | Participants with moderate renal impairment (eGFR 30 to 59 mL/min) will receive single oral dose of JNJ-42847922 on Day 1. |
| Lead-in period: Placebo | PLACEBO_COMPARATOR | Participants who successfully complete the baseline examination visit at the clinical site/unit, will be treated with placebo (2 capsules taken orally) for the duration of the lead-in period which will last up to 3 weeks. Investigators and participants will be blinded to exact duration of each participant-specific lead-in period throughout the study. |
| Treatment period: JNJ-42847922 or Placebo | EXPERIMENTAL | Placebo lead-in period responders and non-responders will be randomized to receive either placebo or 20 milligram (mg) JNJ-42847922 or 40 mg JNJ-42847922 for 5 Weeks. Participants will swallow JNJ-42847922 20 mg (2\*10-mg capsules) or JNJ-42847922 40 mg (2\*20-mg capsules) or 2 matching placebo capsules once daily for 5 Weeks. |
| Withdrawal period: Placebo | PLACEBO_COMPARATOR | Participants who will complete the treatment period prior to the end of Week 8 will enter the withdrawal period where they will be treated with placebo (2 capsules taken orally) for the remaining time of the double-blind phase of the study. Investigators and participants will be blinded to exact duration of each participant-specific withdrawal period. |
| JNJ-42847922 and Rifampin | EXPERIMENTAL | A single oral dose of 40 milligram (mg) (=2\*20 mg) dose of JNJ-42847922 on Day 1; A single oral dose of 40 mg (=2\*20 mg) dose of JNJ-42847922 dosed with one oral dose of rifampin 600 mg (2\*300 mg) on Day 5; A single oral dose of 40 mg (=2\*20 mg) dose of JNJ-42847922 dosed on Day 12, following once daily dosing of rifampin with an oral dose of rifampin 600 mg (2\*300 mg) on Days 5-12. |
| Group 1 (Sequence ABC) | EXPERIMENTAL | Participants will receive Treatment A (2 capsules of 20 milligram \[mg\] JNJ-42847922) in Period 1, Treatment B (10 mg zolpidem and 1 placebo capsule) in Period 2 and Treatment C (2 placebo capsules) in Period 3 with a washout interval of at least 3 days between treatment periods. Participants randomized to this group will be assessed for pharmacodynamic testing at 2 and 6 hours after dosing. |
| Group 2 (Sequence BCA) | EXPERIMENTAL | Participants will receive Treatment B in Period 1, Treatment C in Period 2 and Treatment A in Period 3 with a washout interval of at least 3 days between treatment periods. Participants randomized to this group will be assessed for pharmacodynamic testing at 2 and 6 hours after dosing. |
| Group 3 (Sequence CAB) | EXPERIMENTAL | Participants will receive Treatment C in Period 1, Treatment A in Period 2 and Treatment B in Period 3 with a washout interval of at least 3 days between treatment periods. Participants randomized to this group will be assessed for pharmacodynamic testing at 2 and 6 hours after dosing. |
| Group 4 (Sequence ABC) | EXPERIMENTAL | Participants will receive Treatment A in Period 1, Treatment B in Period 2 and Treatment C in Period 3 with a washout interval of at least 3 days between treatment periods. Participants randomized to this group will be assessed for pharmacodynamic testing at 4 and 8 hours after dosing. |
| Group 5 (Sequence BCA) | EXPERIMENTAL | Participants will receive Treatment B in Period 1, Treatment C in Period 2 and Treatment A in Period 3 with a washout interval of at least 3 days between treatment periods. Participants randomized to this group will be assessed for pharmacodynamic testing at 4 and 8 hours after dosing. |
| Group 6 (Sequence CAB) | EXPERIMENTAL | Participants will receive Treatment C in Period 1, Treatment A in Period 2 and Treatment B in Period 3 with a washout interval of at least 3 days between treatment periods. Participants randomized to this group will be assessed for pharmacodynamic testing at 4 and 8 hours after dosing. |
| JNJ-42847922 Plus Midazolam Plus Warfarin | EXPERIMENTAL | Participants will receive Treatment A (midazolam 4 milligram \[mg\] syrup once on Day 1 and warfarin 25 mg tablet once on Day 3) followed by Treatment B (JNJ-42847922 20 mg once daily from Day 1 to Day 9, midazolam 4 mg syrup once on Day 7 and warfarin 25 mg tablet once on Day 9). A washout period of 14 to 21 days will be maintained between each treatment period. |
| Cohort A | EXPERIMENTAL | Participants will receive single oral dose of 5 milligram (mg) of JNJ-42847922 or Placebo on Day 1, fasted condition. |
| Cohort B | EXPERIMENTAL | Participants will receive single oral dose of 20 mg of JNJ-42847922 or Placebo on Day 1, fasted condition. |
| Cohort C | EXPERIMENTAL | Participants will receive single oral dose of 40 mg of JNJ-42847922 or Placebo on Day 1, fasted condition. |
| Diphenhydramine | EXPERIMENTAL | Diphenhydramine 25 mg capsule, orally, once daily, at bedtime for 10 days in women of childbearing potential (WOCBP) or for 4 weeks in all other participants. |
| JNJ-42847922 Plus Rabeprazole | EXPERIMENTAL | Participants will receive JNJ-42847922, 20 milligram (mg) on Day 1 and Day 6. Participants will receive rabeprazole 20 mg once daily from Day 2 to Day 6. |
| JNJ-42847922 plus Itraconazole | EXPERIMENTAL | Participants will receive single dose of 5 milligram (mg) JNJ-42847922 as 5 mg/milliliter \[mL\] oral solution on Day 1 and Day 6 and itraconazole as 200 mg (2\*100 mg capsule) from Day 2 to Day 6. |
| JNJ-42847922, 5 milligram (mg) and Placebo | EXPERIMENTAL | Participants will be receive either 5 mg of JNJ-42847922 from Day 1 up to Day 10 or matching placebo from Day 1 up to Day 10. |
| JNJ-42847922, 10 mg and Placebo | EXPERIMENTAL | Participants will be receive either 10 mg of JNJ-42847922 from Day 1 up to Day 10 or matching placebo from Day 1 up to Day 10. |
| JNJ-42847922, 20 mg and Placebo | EXPERIMENTAL | Participants will be receive either 20 mg of JNJ-42847922 from Day 1 up to Day 10 or matching placebo from Day 1 up to Day 10. |
| JNJ-42847922, 40 mg and Placebo | EXPERIMENTAL | Participants will be receive either 40mg of JNJ-42847922 from Day 1 up to Day 10 or matching placebo from Day 1 up to Day 10. |
| Cohort D | EXPERIMENTAL | 5 participants will be included in this cohort. Participants will receive the study medications in the sequence of JNJ-42847922 40 mg (Period 1), JNJ-42847922 20 mg (Period 2), JNJ-42847922 10 mg (Period 3), and placebo (Period 4). Each subsequent treatment period will be separated by 1 week. |
| Name | Type | Description |
|---|---|---|
| JNJ-42847922 | DRUG | Participants will receive JNJ-42847922 capsule orally. |
| Placebo Matching to JNJ-42847922 | DRUG | Participants will receive placebo capsule matching to JNJ-42847922 orally. |
| Quetiapine XR | DRUG | Participants will receive quetiapine XR capsule orally. |
| Placebo Matching to Quetiapine XR | DRUG | Participants will receive placebo capsule matching to quetiapine XR orally. |
| Selective Serotonin Reuptake Inhibitor (SSRI) | DRUG | 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). |
| Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) | DRUG | 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). |
| Placebo | DRUG | Matching placebo will be administered once daily based upon dosing group. |
| JNJ-42847922, 5 mg | DRUG | JNJ-42847922 will be administered as 5 mg (2\*2.5 mg capsule) oral capsules once daily. |
| JNJ-42847922, 10 mg | DRUG | JNJ-42847922 will be administered as 10 mg oral capsule once daily. |
| JNJ-42847922, 20 mg | DRUG | JNJ-42847922 will be administered as 20 mg oral capsule once daily. |
| Zolpidem | DRUG | Zolpidem will be administered as 5 mg or 10 mg (2\*5mg capsule) oral capsule once daily based upon the local labeling information. |
| JNJ-42847922 20mg | DRUG | Participants will swallow 20 mg (2\*10 mg) JNJ-42847922 capsule orally for 5 weeks during treatment period. |
| JNJ-42847922 40mg | DRUG | Participants will swallow 40 mg (2\*20 mg) JNJ-42847922 capsule orally for 5 weeks during treatment period. |
| Rifampin | DRUG | Oral dose of rifampin 600 mg (2\*300 mg) on Day 5 and once daily dosing of rifampin with an oral dose of rifampin 600 mg (2\*300 mg) on Days 5 to 12. |
| Midazolam | DRUG | Participants will receive midazolam 4 milligram (mg) syrup orally once on Day 1 during treatment A and on Day 7 during treatment B. |
| Warfarin | DRUG | Participants will receive warfarin 25 milligram (mg) tablet orally once on Day 3 during treatment A and on Day 9 during treatment B. |
| JNJ-42847922, 40 mg | DRUG | Participants will receive single oral dose of 40 mg of JNJ-42847922 on Day 1, fasted condition. |
| Diphenhydramine | DRUG | Diphenhydramine 25 mg capsule, orally, once daily, at bedtime for 10 days in women of childbearing potential (WOCBP) or for 4 weeks in all other participants. |
| Rabeprazole | DRUG | Rabeprazole will be administered as 20 mg tablet orally. |
| Itraconazole | DRUG | Participants will receive single dose of itraconazole as 200 mg (2\*100 mg capsule) from Day 2 to Day 6. |
| JNJ-42847922 5 mg | DRUG | Participants will receive 5 mg of JNJ-42847922, from Day 1 up to Day 10. |
| JNJ-42847922 10 mg | DRUG | Participants will receive 10 mg of JNJ-42847922, from Day 1 up to Day 10. |
| JNJ-42847922 20 mg | DRUG | Participants will receive 20 mg of JNJ-42847922, from Day 1 up to Day 10. |
| JNJ-42847922 40 mg | DRUG | Participants will receive 40 mg of JNJ-42847922, from Day 1 up to Day 10 . |
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 ...
JNJ-42847922 is an investigational small molecule being studied for major depressive disorder, insomnia disorder, and insomnia. It has also been evaluated in healthy volunteers and in people with renal impairment. The drug is in Phase 2 clinical development and is not approved by the FDA.
JNJ-42847922 is being developed by Johnson & Johnson, a company traded on the New York Stock Exchange under the ticker JNJ. The drug is a small molecule in the psychiatry therapeutic area, and it is currently in Phase 2 clinical trials.
JNJ-42847922 is in Phase 2 clinical development. It has completed eight clinical trials, including Phase 1 and Phase 2 studies, with a total enrollment of 554 participants. The drug remains investigational and has not been approved by regulatory authorities.
JNJ-42847922 has been studied in several completed trials. NCT02067299 examined its effect on sleep measures in major depressive disorder with insomnia. NCT02464046 and NCT03375203 evaluated it in insomnia disorder. NCT02476058 assessed safety, efficacy, and biomarkers in major depressive disorder.
Yes, JNJ-42847922 has been studied in major depressive disorder. Trial NCT02476058 evaluated its safety, efficacy, and biomarkers in participants with major depressive disorder. Another study, NCT02067299, looked at its effect on sleep in patients with major depressive disorder with insomnia who were on stable antidepressants.
Yes, JNJ-42847922 has been studied in insomnia. Trial NCT02464046 evaluated its efficacy, safety, and tolerability in participants with insomnia disorder without psychiatric comorbidity. A larger study, NCT03375203, assessed its efficacy, safety, and tolerability in 365 participants with insomnia disorder.