Trial Outcomes & Findings for Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients (NCT NCT02466685)

Last Updated: 2023-11-14

Results Overview

Change in a score of Verbal Fluency from baseline to week 8 A higher amount of change represents a better outcome V.F., as a primary outcome measure, is one of the Cognitive battery tests used to evaluate neurocognitive functions, i.e., speed of processing, attention/vigilance, working memory, verbal learning, and visual learning. The way to calculate the score: the participant is asked to produce as many words as possible from a category in a given time and each correct word gets 1 score Min raw score:0 Max raw score:60

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Baseline and week 8

Results posted on

2023-11-14

Participant Flow

Participant milestones

Participant milestones
Measure	JNJ-18038683 Subjects will be randomized to receive JNJ-18038683 or placebo after the completion of the baseline assessments. Subjects randomized to JNJ-18038683 will receive 10 mg for one week, then titrate to 20 mg for the duration of the trial, with the provision for a single, downward dose adjustment for intolerance, based upon investigator judgment. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Placebo Placebo treatment for 8 weeks. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks
Overall Study STARTED	30	30
Overall Study COMPLETED	22	26
Overall Study NOT COMPLETED	8	4

Reasons for withdrawal

Reasons for withdrawal
Measure	JNJ-18038683 Subjects will be randomized to receive JNJ-18038683 or placebo after the completion of the baseline assessments. Subjects randomized to JNJ-18038683 will receive 10 mg for one week, then titrate to 20 mg for the duration of the trial, with the provision for a single, downward dose adjustment for intolerance, based upon investigator judgment. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Placebo Placebo treatment for 8 weeks. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks
Overall Study Adverse Event	5	2
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	1	0
Overall Study Physician Decision	1	1

Baseline Characteristics

Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	JNJ-18038683 n=30 Participants Subjects will be randomized to receive JNJ-18038683 or placebo after the completion of the baseline assessments. Subjects randomized to JNJ-18038683 will receive 10 mg for one week, then titrate to 20 mg for the duration of the trial, with the provision for a single, downward dose adjustment for intolerance, based upon investigator judgment. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Placebo n=30 Participants Placebo treatment for 8 weeks. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants	30 Participants n=7 Participants	60 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	39.1 years STANDARD_DEVIATION 12.1 • n=5 Participants	37.4 years STANDARD_DEVIATION 11.0 • n=7 Participants	38.2 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	16 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	14 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	19 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	30 participants n=7 Participants	60 participants n=5 Participants
Verbal Fluency	35.87 units on a scale STANDARD_DEVIATION 2.12 • n=5 Participants	40.07 units on a scale STANDARD_DEVIATION 2.16 • n=7 Participants	38.82 units on a scale STANDARD_DEVIATION 2.14 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 8

Population: Although the total number of participants in each group was 30, the analysis was only done for those who had completed all study visits.

Outcome measures

Outcome measures
Measure	JNJ-18038683 n=22 Participants JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Placebo n=26 Participants Placebo treatment for 8 weeks. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks
The 8-week Evaluation of Verbal Fluency Performance After Randomization	39.44 score on a scale Standard Error 1.31	41.12 score on a scale Standard Error 1.33

SECONDARY outcome

Timeframe: Baseline to week 8

Population: Although the total number of each group was 30, only data of the participants who completed week eight were analyzed on MADRS. ANCOVA analysis for comparing the result of the Montgomery Asberg Depression rating scale between JNJ-18038683 and the placebo group, based on the least-square means and standard errors, will be the statistical method. The Missing data will be imputed by MMRM.

Secondary outcome measures will include mean changes of the Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 8. The MADRS will be utilized to assess a subject's level of depressive symptoms and must be administered using a structured interview guide. This scale consists of 10 items, each with seven defined grades of severity (zero to six), and min score of 0, and a max score of 60. Higher values represent a worse outcome. Notably, mean changes were not statistically significant in both groups.

Outcome measures

Outcome measures
Measure	JNJ-18038683 n=22 Participants JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Placebo n=26 Participants Placebo treatment for 8 weeks. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks
Montgomery-Asberg Depression Rating Scale MADRS baseline score	2.93 score on a scale Standard Error 0.71	3.37 score on a scale Standard Error 0.71
Montgomery-Asberg Depression Rating Scale MADRS week 8 score	6.63 score on a scale Standard Error 1.26	5.89 score on a scale Standard Error 1.26

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: Although the total number of participants in each group was 30, the analysis was only done for those who had completed all study visits. Using ANCOVA analysis to assess changes from baseline to week 8, based on the least-square means and standard errors was the method.

We assessed the clinical global Impression severity (CGI-S) scores change in JNJ-18038683 and the placebo group as an additional endpoint. The scale rates the subject's Severity of Illness (CGI-BPSeverity: mania, depression, and overall bipolar illness). Using ANCOVA analysis to assess changes from baseline to week 8, based on the least-square means and standard errors was the method. CGI-S scores range from 0 to 7. Higher scores mean a worse outcome.

Outcome measures

Outcome measures
Measure	JNJ-18038683 n=22 Participants JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Placebo n=26 Participants Placebo treatment for 8 weeks. JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks
Clinical Global Impression Severity of the Subject With Bipolar Disorder Scale( CGI-S in BP) Change From Baseline to Week 8 CGI-S baseline score	2.78 score on a scale Standard Error 0.19	2.63 score on a scale Standard Error 0.19
Clinical Global Impression Severity of the Subject With Bipolar Disorder Scale( CGI-S in BP) Change From Baseline to Week 8 CGI-S week 8 score	2.59 score on a scale Standard Error 0.19	2.37 score on a scale Standard Error 0.19

Adverse Events

JNJ-18038683

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	JNJ-18038683 n=30 participants at risk JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Placebo n=30 participants at risk Placebo treatment for 8 weeks.
Psychiatric disorders Serious Adverse Event	6.7% 2/30 • Number of events 3 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	3.3% 1/30 • Number of events 1 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%
Gastrointestinal disorders Serious Adverse events	3.3% 1/30 • Number of events 1 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	0.00% 0/30 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%

Other adverse events

Other adverse events
Measure	JNJ-18038683 n=30 participants at risk JNJ-18038683: JNJ-18038683 10-20 mg/day for 8 weeks	Placebo n=30 participants at risk Placebo treatment for 8 weeks.
Psychiatric disorders Non-Serious Adverse Events	6.7% 2/30 • Number of events 2 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	0.00% 0/30 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%
Gastrointestinal disorders Non-Serious Adverse Events	6.7% 2/30 • Number of events 3 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	0.00% 0/30 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%
Respiratory, thoracic and mediastinal disorders Non-Serious Adverse Events	0.00% 0/30 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	6.7% 2/30 • Number of events 2 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%
Psychiatric disorders Non-Seriuos Adverse event	0.00% 0/30 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	6.7% 2/30 • Number of events 2 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%
General disorders Non-Serious Adverse Events	6.7% 2/30 • Number of events 2 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	0.00% 0/30 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%
Ear and labyrinth disorders Non-Serious Adverse Events	6.7% 2/30 • Number of events 2 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	0.00% 0/30 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%
Nervous system disorders Non-Serious Adverse Events	6.7% 2/30 • Number of events 5 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%	16.7% 5/30 • Number of events 5 • During the study, from baseline to week12 (from baseline to 4 weeks after the study completion) The total number affected by any Serious Adverse Event was 4 patients but 5 events. Regarding Non-Serious Adverse Events, reports are according to the threshold of 5%

Additional Information

Mahdi Arshadi

Northwestern University

Phone: 3123839950

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place