Trial Outcomes & Findings for A Study to Explore the Efficacy of JNJ-67953964 in the Treatment of Depression (NCT NCT03559192)
NCT ID: NCT03559192
Last Updated: 2025-04-29
Results Overview
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts. Negative change from baseline indicates improvement.
COMPLETED
PHASE2
181 participants
Treatment Baseline up to Week 6 of DB-treatment period
2025-04-29
Participant Flow
Participant milestones
| Measure |
Lead in Period: Placebo
Participants who successfully completed the baseline examination visit at the clinical site/unit, were treated with placebo for the entire duration of the lead-in period (up to 3 weeks).
|
Double-blind Treatment + Withdrawal Period: Placebo
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|---|
|
Lead-in Period (3 Weeks)
STARTED
|
181
|
0
|
0
|
|
Lead-in Period (3 Weeks)
COMPLETED
|
169
|
0
|
0
|
|
Lead-in Period (3 Weeks)
NOT COMPLETED
|
12
|
0
|
0
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
STARTED
|
0
|
84
|
85
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Placebo Lead-in Responders
|
0
|
22
|
23
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Placebo Lead-In Non-Responders
|
0
|
62
|
62
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Completed DB Period and Entered Withdrawal
|
0
|
81
|
80
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
COMPLETED
|
0
|
81
|
79
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
NOT COMPLETED
|
0
|
3
|
6
|
Reasons for withdrawal
| Measure |
Lead in Period: Placebo
Participants who successfully completed the baseline examination visit at the clinical site/unit, were treated with placebo for the entire duration of the lead-in period (up to 3 weeks).
|
Double-blind Treatment + Withdrawal Period: Placebo
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|---|
|
Lead-in Period (3 Weeks)
Protocol Violation
|
1
|
0
|
0
|
|
Lead-in Period (3 Weeks)
Withdrawal by Subject
|
6
|
0
|
0
|
|
Lead-in Period (3 Weeks)
Adverse Event
|
5
|
0
|
0
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Protocol Violation
|
0
|
0
|
1
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Withdrawal by Subject
|
0
|
1
|
0
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Lack of Efficacy
|
0
|
0
|
2
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Adverse Event
|
0
|
1
|
1
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Non-compliance with study drug
|
0
|
0
|
1
|
|
DB Treatment(6 Wks) + Withdrawal(2 Wks)
Other
|
0
|
1
|
1
|
Baseline Characteristics
A Study to Explore the Efficacy of JNJ-67953964 in the Treatment of Depression
Baseline characteristics by cohort
| Measure |
Lead in Period: Placebo
n=181 Participants
Participants who successfully completed the baseline examination visit at the clinical site/unit, were treated with placebo for the entire duration of the lead-in period (up to 3 weeks).
|
|---|---|
|
Age, Continuous
|
42.5 years
STANDARD_DEVIATION 12.91 • n=5 Participants
|
|
Age, Customized
Adults (18-64 years)
|
181 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
131 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
156 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
167 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: The enriched intent-to-treat (eITT) analysis set included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts. Negative change from baseline indicates improvement.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=59 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=59 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Treatment Week 6 in Participants Who Were Non-Responders During Placebo Lead-in Period
|
-8.0 scores on a scale
Standard Error 0.92 • Interval 0.92 to
|
-10.1 scores on a scale
Standard Error 0.93 • Interval 0.93 to
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: The full intent-to-treat (fITT) analysis set included all enrolled participants who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-treatment baseline assessment of MADRS during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts. Negative change from baseline indicates improvement.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=81 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=77 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in MADRS Total Score at Treatment Week 6
|
-6.5 scores on a scale
Standard Error 0.78 • Interval 0.78 to
|
-9.6 scores on a scale
Standard Error 0.79 • Interval 0.79 to
|
SECONDARY outcome
Timeframe: Up to Week 6Population: The full safety analysis set included all enrolled participants who received at least 1 dose of study medication in the treatment period.
An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product. TEAEs were AEs with onset during the treatment period that has worsened since baseline.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=84 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=85 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During DB Treatment Period
|
30 Participants
|
40 Participants
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: The eITT analysis set included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) includes the number of participants evaluable for this outcome measure.
The SHAPS is a self-reported 14-item, instrument, developed for the assessment of hedonic capacity. Participants scored whether they experienced pleasure in performing a list of activities or experiences. Participants rated the answers as 1-4 where 1 indicates "Definitely agree", 2 indicates "Agree", 3 indicates "Disagree" and 4 indicates "Definitely disagree". The participant's item responses were summed to provide a total score ranging from 14 to 56. A higher total SHAPS score indicated higher levels of current anhedonia. Negative change from baseline indicated improvement.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=59 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=59 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score at Treatment Week 6 (eITT Population)
|
-3.7 scores on a scale
Standard Error 0.64 • Interval 0.64 to
|
-4.4 scores on a scale
Standard Error 0.64 • Interval 0.64 to
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: The fITT analysis set included all enrolled participants who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-treatment baseline assessment of MADRS during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
The SHAPS is a self-reported 14-item, instrument, developed for the assessment of hedonic capacity. Participants scored whether they experienced pleasure in performing a list of activities or experiences. Participants rated the answers as 1-4 where 1 indicates "Definitely agree", 2 indicates "Agree", 3 indicates "Disagree" and 4 indicates "Definitely disagree". The participant's item responses were summed to provide a total score ranging from 14 to 56. A higher total SHAPS score indicated higher levels of current anhedonia. Negative change from baseline indicated improvement.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=81 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=77 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in SHAPS Total Score at Treatment Week 6 (fITT)
|
-3.7 scores on a scale
Standard Error 0.55
|
-4.5 scores on a scale
Standard Error 0.55
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: eITT analysis set included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, had at least 1 post-baseline MADRS assessment during treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
CGI-S provides an overall clinician-determined summary measure of severity of participant's illness that considers all available information, including knowledge of participant's history, psychosocial circumstances, symptoms, behavior, and impact of symptoms on participant's ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Participant is assessed on severity of mental illness at time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill participants. Negative change in score indicates improvement.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=59 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=59 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in Clinical Global Impression - Severity (CGI-S) Score at Treatment Week 6 (eITT Population)
|
-0.76 Scores on a scale
Standard Deviation 0.858 • Interval 0.858 to
|
-0.92 Scores on a scale
Standard Deviation 1.039 • Interval 1.039 to
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: fITT analysis set included all enrolled participants who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-treatment baseline assessment of MADRS during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
CGI-S provides an overall clinician-determined summary measure of severity of participants illness that considers all available information, including knowledge of participant's history, psychosocial circumstances, symptoms, behavior, and impact of symptoms on participant's ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Participant is assessed on severity of mental illness at time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill participants. Negative change in score indicates improvement.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=81 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=77 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in CGI-S Score at Treatment Week 6 (fITT Population)
|
-0.67 Scores on a scale
Standard Deviation 0.880
|
-0.87 Scores on a scale
Standard Deviation 1.005
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: The eITT analysis set included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
The SMDDS is a 16-item patient reported outcome (PRO) measure. Each item was rated by the participant according to a 5-point Likert scale. 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") were combined into a single score by selecting the highest severity on either item. The total score was then created by summing the responses on the 15 items. The total score ranged from 0 to 60. The SMDDS uses a 7-day recall period and verbal rating scales. Higher score indicates more severe depressive symptomatology. Negative change from baseline indicates improvement.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=59 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=59 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Treatment Week 6 (eITT Population)
|
-8.49 Scores on a scale
Standard Deviation 9.567 • Interval 9.567 to
|
-8.03 Scores on a scale
Standard Deviation 9.957 • Interval 9.957 to
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: fITT analysis set included all enrolled participants who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-treatment baseline assessment of MADRS during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
The SMDDS is a 16-item patient reported outcome (PRO) measure. Each item was rated by the participant according to a 5-point Likert scale. 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") were combined into a single score by selecting the highest severity on either item. The total score was then created by summing the responses on the 15 items. The total score ranged from 0 to 60. The SMDDS uses a 7-day recall period and verbal rating scales. Higher score indicates more severe depressive symptomatology. Negative change from baseline indicates improvement.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=81 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=80 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in SMDDS Total Score at Treatment Week 6 (fITT Population)
|
-6.91 Scores on a scale
Standard Deviation 9.996
|
-8.16 Scores on a scale
Standard Deviation 9.470
|
SECONDARY outcome
Timeframe: Treatment Week 6Population: The eITT analysis set included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'n' (number analyzed) refers to all participants evaluable for specified categories. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
SATE questionnaire is a 3-item self-reported scale designed to provide additional information regarding participant's subjective experience while taking treatment. This was internal Janssen questionnaire and questions were asked to participant weekly by the Q1.6-app. For rating overall depression: participant selected one option out of Improved, not changed or got worse; for depression improvement: participant selected one option out of slightly improved, much improved or very much improved; and for depression worsen: participant selected slightly worse, much worse or very much worse.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=40 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=30 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Overall Depression (Got worse)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Overall Depression (Not changed)
|
12 Participants
|
9 Participants
|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Overall Depression (Improved)
|
27 Participants
|
21 Participants
|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Depression Worsened (Slightly worse)
|
1 Participants
|
—
|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Depression Worsened (Much worse)
|
0 Participants
|
—
|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Depression Worsened (Very much worse)
|
0 Participants
|
—
|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Depression Improvement (Slightly improved)
|
13 Participants
|
15 Participants
|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Depression Improvement (Much improved)
|
11 Participants
|
6 Participants
|
|
Number of Participants With Self-Assessment of Treatment Experience (SATE) Questionnaire at Treatment Week 6 (eITT Population)
Depression Improvement (Very Much Improved)
|
3 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Treatment Week 6Population: (fITT) analysis set included all enrolled participants who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-treatment baseline assessment of MADRS during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure. Here 'n' (number analyzed) refers to all participants evaluable for specified categories.
SATE questionnaire is a 3-item self-reported scale designed to provide additional information regarding participant's subjective experience while taking treatment. This was internal Janssen questionnaire and questions were asked to participant weekly by the Q1.6-app. For rating overall depression: participant selected one option out of Improved, not changed or got worse; for depression improvement: participant selected one option out of slightly improved, much improved or very much improved; and for depression worsen: participant selected slightly worse, much worse or very much worse.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=49 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=42 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Overall Depression (Got worse)
|
1 Participants
|
0 Participants
|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Overall Depression (Not changed)
|
15 Participants
|
12 Participants
|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Overall Depression (Improved)
|
33 Participants
|
30 Participants
|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Depression Worsened (Slightly worse)
|
1 Participants
|
—
|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Depression Worsened (Much worse)
|
0 Participants
|
—
|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Depression Worsened (Very much worse)
|
0 Participants
|
—
|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Depression Improvement (Slightly improved)
|
18 Participants
|
20 Participants
|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Depression Improvement (Much improved)
|
12 Participants
|
9 Participants
|
|
Number of Participants With SATE Questionnaire at Treatment Week 6 (fITT Population)
Depression Improvement (Very Much Improved)
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: eITT analysis set included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
HAM-A scale assesses severity of different anxiety-related symptoms with a score range of 0 to 52. Higher score indicated severity in anxiety symptoms. Each of the 14 items is rated by clinician on a 5-point scale ranging from 0 (not present) to 4 (maximum degree). HAM-A6 is a uni-dimensional, 6-item subscale derived from HAM-A. HAM-A6 comprises of five psychic anxiety symptoms: anxious mood, psychic tension, fears, intellectual disturbances, and anxious behaviour observed at the interview, as well as one somatic item, muscular tension. HAM-A6 subscale score ranges from 0 to 24, with higher scores indicating greater severity of core symptoms.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=59 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=59 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in Hamilton Anxiety Scale 6 (HAM-A6) Total Score at Treatment Week 6 (eITT Population)
|
-2.19 scores on a scale
Standard Deviation 2.837 • Interval 2.837 to
|
-2.73 scores on a scale
Standard Deviation 2.651 • Interval 2.651 to
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: (fITT) analysis set included all enrolled participants who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-treatment baseline assessment of MADRS during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
HAM-A scale assesses severity of different anxiety-related symptoms with a score range of 0 to 52. Higher score indicated severity in anxiety symptoms. Each of the 14 items is rated by clinician on a 5-point scale ranging from 0 (not present) to 4 (maximum degree). HAM-A6 is a uni-dimensional, 6-item subscale derived from HAM-A. HAM-A6 comprises of five psychic anxiety symptoms: anxious mood, psychic tension, fears, intellectual disturbances, and anxious behaviour observed at the interview, as well as one somatic item, muscular tension. HAM-A6 subscale score ranges from 0 to 24, with higher scores indicating greater severity of core symptoms.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=81 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=77 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in HAM-A6 Total Score at Treatment Week 6 (fITT)
|
-1.67 scores on a scale
Standard Deviation 2.842
|
-2.68 scores on a scale
Standard Deviation 2.562
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: The eITT analysis set included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
SIGH-A is a 14-item scale to measure severity of different anxiety-related symptoms in participants. Each of the 14 items is rated by the clinician on a 5-point scale ranging from 0 (not present) to 4 (maximum degree). The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56 where higher score indicates worsening.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=59 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=59 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) Score at Treatment Week 6 (eITT Population)
|
-5.37 scores on a scale
Standard Deviation 6.549 • Interval 6.549 to
|
-5.85 scores on a scale
Standard Deviation 5.369 • Interval 5.369 to
|
SECONDARY outcome
Timeframe: Treatment Baseline up to Week 6 of DB-treatment periodPopulation: fITT analysis set included all enrolled participants who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-treatment baseline assessment of MADRS during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
SIGH-A is a 14-item scale to measure severity of different anxiety-related symptoms in participants. Each of the 14 items is rated by the clinician on a 5-point scale ranging from 0 (not present) to 4 (maximum degree). The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56 where higher score indicates worsening.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=81 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=77 Participants
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Change From Treatment Baseline in SIGH-A Score at Treatment Week 6 (fITT Population)
|
-4.35 scores on a scale
Standard Deviation 6.193
|
-5.47 scores on a scale
Standard Deviation 4.988
|
SECONDARY outcome
Timeframe: Week 1: Day 29, Week 3: Day 43, Week 6 (Day 64)Population: eITT population included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure. Here 'n' (number analyzed) refers to all participants evaluable for specified time point categories.
Cmax was defined as maximum observed plasma concentration of JNJ-67953964.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=58 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of JNJ-67953964
Week 1 (Day 29)
|
32.7 nanograms per milliliter (ng/mL)
Standard Deviation 10.9
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) of JNJ-67953964
Week 3 (Day 43)
|
33.5 nanograms per milliliter (ng/mL)
Standard Deviation 11.1
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) of JNJ-67953964
Week 6 (Day 64)
|
34.3 nanograms per milliliter (ng/mL)
Standard Deviation 11.1
|
—
|
SECONDARY outcome
Timeframe: 0 to 24 hours Post dose on Week 1: Day 29, Week 3: Day 43, Week 6: Day 64Population: eITT population included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure. Here 'n' (number analyzed) refers to all participants evaluable for specified time point categories.
AUC(0-24h) was defined as the area under the plasma concentration-time curve from time of administration to 24 hours.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=58 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC[0-24h]) of JNJ-67953964
Week 6 (Day 64)
|
378 nanograms*hour per milliliter (ng*h/mL)
Standard Deviation 163
|
—
|
|
Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC[0-24h]) of JNJ-67953964
Week 1 (Day 29)
|
361 nanograms*hour per milliliter (ng*h/mL)
Standard Deviation 156
|
—
|
|
Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC[0-24h]) of JNJ-67953964
Week 3 (Day 43)
|
377 nanograms*hour per milliliter (ng*h/mL)
Standard Deviation 164
|
—
|
SECONDARY outcome
Timeframe: Week 1: Day 29, Week 3: Day 43, Week 6: Day 64Population: eITT population included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure. Here 'n' (number analyzed) refers to all participants evaluable for specified time point categories.
AUCss was defined as the area under plasma concentration-time curve at Steady State (AUCss) of JNJ-67953964.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=58 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Area Under Plasma Concentration-Time Curve at Steady State (AUCss) of JNJ-67953964
Week 1 (Day 29)
|
380 ng*h/mL
Standard Deviation 151
|
—
|
|
Area Under Plasma Concentration-Time Curve at Steady State (AUCss) of JNJ-67953964
Week 3 (Day 43)
|
380 ng*h/mL
Standard Deviation 151
|
—
|
|
Area Under Plasma Concentration-Time Curve at Steady State (AUCss) of JNJ-67953964
Week 6 (Day 64)
|
379 ng*h/mL
Standard Deviation 153
|
—
|
SECONDARY outcome
Timeframe: Predose on Week 1: Day 29, Week 3: Day 43, Week 6: Day 64Population: eITT population included all enrolled lead-in placebo non-responders who were randomized into a treatment period, received at least 1 dose of study medication, and had at least 1 post-baseline MADRS assessment during the treatment period. Here 'N' (number of participants analyzed) refers to the number of participants evaluable for this outcome measure. Here 'n' (number analyzed) refers to all participants evaluable for specified time point categories.
C0h was defined as predose plasma Concentration of JNJ-67953964.
Outcome measures
| Measure |
Double-blind Treatment + Withdrawal Period: Placebo
n=58 Participants
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|
|
Predose (Trough) Plasma Concentration (C0h) of JNJ-67953964
Week 1 (Day 29)
|
8.62 nanograms per milliliter (ng/ml)
Standard Deviation 4.27
|
—
|
|
Predose (Trough) Plasma Concentration (C0h) of JNJ-67953964
Week 3 (Day 43)
|
9.40 nanograms per milliliter (ng/ml)
Standard Deviation 4.69
|
—
|
|
Predose (Trough) Plasma Concentration (C0h) of JNJ-67953964
Week 6 (Day 64)
|
9.48 nanograms per milliliter (ng/ml)
Standard Deviation 4.83
|
—
|
Adverse Events
Lead in Period: Placebo
Double-blind Treatment + Withdrawal Period: Placebo
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
Serious adverse events
| Measure |
Lead in Period: Placebo
n=169 participants at risk
Participants who successfully completed the baseline examination visit at the clinical site/unit, were treated with placebo for the entire duration of the lead-in period (up to 3 weeks).
|
Double-blind Treatment + Withdrawal Period: Placebo
n=84 participants at risk
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=85 participants at risk
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|---|
|
Hepatobiliary disorders
Cholecystitis Acute
|
0.00%
0/169 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
1.2%
1/84 • Number of events 1 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
0.00%
0/85 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
Other adverse events
| Measure |
Lead in Period: Placebo
n=169 participants at risk
Participants who successfully completed the baseline examination visit at the clinical site/unit, were treated with placebo for the entire duration of the lead-in period (up to 3 weeks).
|
Double-blind Treatment + Withdrawal Period: Placebo
n=84 participants at risk
Participants who were responders (30 percent \[%\]) or more improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) total score during the placebo run-in) or non-responders to lead-in placebo group were re-randomized to receive placebo matching to JNJ-67953964 capsules (2 placebo capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to Selective serotonin reuptake inhibitors /Serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
Double-blind Treatment + Withdrawal Period: JNJ-67953964 10 Milligrams (mg)
n=85 participants at risk
Participants who were responders (30% or more improvement on the MADRS total score during the placebo run-in were responders) or non-responders to lead-in placebo group were re-randomized to receive 10 mg JNJ-67953964 capsules (2\*5 mg JNJ-67953964 capsules) once daily during double-blind treatment period (up to 6 weeks after lead-in period) in addition to SSRI/SNRI treatment. Participants who completed the double-blind treatment period prior to the end of Week 11 entered the withdrawal period where they were treated with placebo for 2 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
3.6%
6/169 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
2.4%
2/84 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
8.2%
7/85 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
|
Infections and infestations
Nasopharyngitis
|
3.6%
6/169 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
3.6%
3/84 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
7.1%
6/85 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
|
Nervous system disorders
Headache
|
6.5%
11/169 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
8.3%
7/84 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
11.8%
10/85 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.59%
1/169 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
0.00%
0/84 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
5.9%
5/85 • Up to Week 11
Full Safety analysis set included all enrolled participants who received at least 1 dose of study drug in treatment period.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER