Trial Outcomes & Findings for Monotherapy Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Schizophrenia With Impulsivity (NCT NCT02194933)

NCT ID: NCT02194933

Last Updated: 2018-11-08

Results Overview

To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants perform tasks designed to assess impulsivity. The tasks to be performed in the scanner included the Go/No-go. Participants were asked to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) \& to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The Go trials were presented at a higher frequency (eg, 75% of the time) than the No-go trials to build up a pre-potent response/response bias. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 38 participants
• Primary outcome timeframe: At baseline (Day 0), and week 6 (Day 42) of the treatment phase
• Results posted on: 2018-11-08

Participant Flow

The study was conducted in the United States (US). 38 participants with schizophrenia with impulsivity were enrolled (signed informed consent) and randomized (1:1): 19 participants to brexpiprazole 2mg and 4mg treatment each; received at least 1 dose of Investigational medicinal product (IMP) for 6-week treatment phase in a double-blind design.

Participants had pretreatment screening phase from 2 to 21 days to assess eligibility criteria, complete screening assessments & to wash out from prior antipsychotic drugs & any other prohibited concomitant drugs; participants were followed for safety by clinic visits/telephone (after first 3 to 4 days of antipsychotic washout & weekly as needed).

Participant milestones

Measure	Brexpiprazole 2 mg Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Overall Study STARTED	19	19
Overall Study COMPLETED	16	10
Overall Study NOT COMPLETED	3	9

Reasons for withdrawal

Measure	Brexpiprazole 2 mg Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Overall Study Lost to Follow-up	1	2
Overall Study Participant met withdrawal criteria	1	3
Overall Study Withdrawal by Subject	0	2
Overall Study Lack of Efficacy	1	2

Baseline Characteristics

Monotherapy Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Schizophrenia With Impulsivity

Baseline characteristics by cohort

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.	Total n=38 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	19 Participants n=5 Participants	19 Participants n=7 Participants	38 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	45.2 Years STANDARD_DEVIATION 10.0 • n=5 Participants	47.4 Years STANDARD_DEVIATION 11.1 • n=7 Participants	46.3 Years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	19 participants n=7 Participants	38 participants n=5 Participants
Race Caucasian (White)	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Race Black or African or American	8 participants n=5 Participants	12 participants n=7 Participants	20 participants n=5 Participants
Race Asian	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race Others	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Ethinicity Hispanic/Latino	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Ethinicity Not Hispanic/Latino	15 participants n=5 Participants	16 participants n=7 Participants	31 participants n=5 Participants

PRIMARY outcome

Timeframe: At baseline (Day 0), and week 6 (Day 42) of the treatment phase

Population: All participants who had a valid baseline and a Week 6 fMRI scan assessment.

To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants perform tasks designed to assess impulsivity. The tasks to be performed in the scanner included the Go/No-go. Participants were asked to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) & to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The Go trials were presented at a higher frequency (eg, 75% of the time) than the No-go trials to build up a pre-potent response/response bias. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task At Week 0	0.06450 units on a scale Standard Error 0.02815	0.06609 units on a scale Standard Error 0.02875
Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task At Week 6	0.04949 units on a scale Standard Error 0.02878	0.04326 units on a scale Standard Error 0.03128

PRIMARY outcome

Timeframe: At baseline (Day 0), and week 6 (Day 42) of the treatment phase

Population: All participants who had a valid baseline and a valid Week 3 or Week 6 fMRI scan assessment.

To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants performed impulsivity assessment tasks. A white circle was shown for 500ms, followed by a left (<)/right (>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 & 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes & 36 seconds. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline Brain Activation in the VLPFC Based on Change From Baseline to Week 6 in fMRI BOLD Activation Score in the Right VLPFC During Performance of the SSRT Task At Week 0	0.05200 units on a scale Standard Error 0.02993	0.09485 units on a scale Standard Error 0.03428
Change From Baseline Brain Activation in the VLPFC Based on Change From Baseline to Week 6 in fMRI BOLD Activation Score in the Right VLPFC During Performance of the SSRT Task At Week 6	-0.00140 units on a scale Standard Error 0.03048	0.002815 units on a scale Standard Error 0.03541

SECONDARY outcome

Timeframe: At baseline (Day 0), and week 3 (Day 21) of the treatment phase

Population: All participants who had a valid baseline and a valid Week 3 fMRI scan assessment

Go/No-go: Participants were to press button fast to Stimulus A (neutral face) (Go trials) & to NOT press button to Stimulus B (happy face) (No-go trials). Task comprised 4 runs of 3 minutes & 8 seconds each. Each run included 36 target (Go) & 13 non target (No-go) stimuli. The stimuli were presented for 500ms with 2 to 14.5 inter-stimulus interval fixation cross in between. Target stimuli were pseudo-randomized across runs so that each participant was presented with 2 Happy Go & 2 Neutral Go conditions.

SSRT: White circle was shown for 500ms, followed by left (<)/right (>) arrow. When an arrow was presented, participants were to respond fast with their index/middle finger. A titration procedure with 4 staircases that started with stop signal delay (SSD) values of 100, 150, 200 & 250ms determined participant's SSRT.

Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task) GNG; Week 0	0.06347 units on a scale Standard Error 0.02801	0.06553 units on a scale Standard Error 0.02869
Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task) GNG; Week 3	0.08523 units on a scale Standard Error 0.02801	0.04973 units on a scale Standard Error 0.02869
Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task) SSRT; Week 0	0.05376 units on a scale Standard Error 0.02903	0.09550 units on a scale Standard Error 0.03346
Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task) SSRT; Week 3	0.06398 units on a scale Standard Error 0.02979	0.02410 units on a scale Standard Error 0.03346

SECONDARY outcome

Timeframe: At baseline (Day 0), and Week 6 (Day 42) of the treatment.

Population: The full analysis set consisted of all participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment. Change from baseline data were presented for participant count of 16, 12 for 2mg and 4mg arms, respectively.

A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.

Outcome measures

Measure	Brexpiprazole 2 mg n=16 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=12 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)	-2.6 units on a scale Standard Error 1.8	1.0 units on a scale Standard Error 2.0

SECONDARY outcome

Timeframe: At baseline (Day 0), and Week 3 (Day 21) of the treatment.

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment. All participants who had a valid baseline and a valid Week 3 or Week 6 fMRI scan assessment.

A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.

Outcome measures

Measure	Brexpiprazole 2 mg n=17 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=16 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in BIS-11	-2.4 units on a scale Standard Error 1.7	-2.3 units on a scale Standard Error 1.7

SECONDARY outcome

Timeframe: At baseline (Day 0), week 6 (Day 42) of the treatment phase

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in Go/No-go Task Behavior At Week 0	0.11 Millisecond Standard Deviation 0.08	0.09 Millisecond Standard Deviation 0.06
Change From Baseline to Week 6 in Go/No-go Task Behavior At Week 6	0.08 Millisecond Standard Deviation 0.09	0.12 Millisecond Standard Deviation 0.17

SECONDARY outcome

Timeframe: At baseline (Day 0), and week 3 (Day 21) of the treatment phase

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in Go/No-go Task Behavior Week 0	0.11 Millisecond Standard Deviation 0.08	0.09 Millisecond Standard Deviation 0.06
Change From Baseline to Week 3 in Go/No-go Task Behavior Week 3	0.10 Millisecond Standard Deviation 0.13	0.15 Millisecond Standard Deviation 0.14

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 6 (Day 42).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

To measure "delay discounting" as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?"). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity. It took 5 to10 minutes to complete the MCQ

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score	-0.019762 units on a scale Standard Error 0.015213	0.023685 units on a scale Standard Error 0.017103

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 3 (Day 21).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

To measure "delay discounting" as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?"). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity.

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in MCQ Score	-0.012073 units on a scale Standard Error 0.014558	0.014520 units on a scale Standard Error 0.014891

SECONDARY outcome

Timeframe: At baseline (Day 0), and Week 6 (Day 42).

Population: All participants who had a valid baseline and a valid Week 6 fMRI scan assessment

Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (<)/right (>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 & 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes & 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with & without a response

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior At Week 0	357.63 Millisecond Standard Deviation 61.51	323.25 Millisecond Standard Deviation 56.59
Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior At Week 6	299.68 Millisecond Standard Deviation 67.77	302.57 Millisecond Standard Deviation 34.68

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 3 (Day 21).

Population: All participants who had a valid baseline and a valid Week 3 fMRI scan assessment

Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). A white circle was shown for 500ms, followed by a left (<)/right (>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 & 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes & 36 seconds. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with & without a response

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in SSRT Task Behavior At week 0	357.63 Millisecond Standard Deviation 61.51	323.25 Millisecond Standard Deviation 56.59
Change From Baseline to Week 3 in SSRT Task Behavior At week 3	337.62 Millisecond Standard Deviation 76.23	328.05 Millisecond Standard Deviation 54.62

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 6 (Day 42).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment

The AX trials were "target trials" with a valid cue followed by a valid probe X. This feature was intended to encourage participants to "expect" a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with "target" responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the "Yes" button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior	-0.70 Rate of correct response Standard Error 3.50	-0.87 Rate of correct response Standard Error 4.06

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 3 (Day 21).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

The AX trials were "target trials" with a valid cue followed by a valid probe X. This feature was intended to encourage participants to "expect" a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with "target" responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the "Yes" button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.

Outcome measures

Measure	Brexpiprazole 2 mg n=14 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=14 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in CPT Behavior	1.79 Rate of correct response Standard Error 4.14	-0.61 Rate of correct response Standard Error 4.08

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 6 (Day 42).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment

The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.

Outcome measures

Measure	Brexpiprazole 2 mg n=16 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=12 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score	-2.4 units on a scale Standard Error 1.9	-4.1 units on a scale Standard Error 2.1

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 3 (Day 21).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment

The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.

Outcome measures

Measure	Brexpiprazole 2 mg n=17 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=16 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in PANSS Total Score	-2.0 units on a scale Standard Error 1.4	-2.3 units on a scale Standard Error 1.4

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 6 (Day 42).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.

Outcome measures

Measure	Brexpiprazole 2 mg n=16 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=12 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in PANSS Positive Subscale Score	-1.4 units on a scale Standard Error 0.9	-1.3 units on a scale Standard Error 1.0

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 3 (Day 21).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.

Outcome measures

Measure	Brexpiprazole 2 mg n=17 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=16 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in PANSS Positive Subscale Score	-1.2 units on a scale Standard Error 0.6	-1.3 units on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 6 (Day 42).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment

PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.

Outcome measures

Measure	Brexpiprazole 2 mg n=16 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=12 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in PANSS Negative Subscale Score	-0.9 units on a scale Standard Error 0.6	0.2 units on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 3 (Day 21).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.

Outcome measures

Measure	Brexpiprazole 2 mg n=17 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=16 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in PANSS Negative Subscale Score	0.2 units on a scale Standard Error 0.7	0.8 units on a scale Standard Error 0.7

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 6 (Day 42).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

The severity of illness for each participant was assessed. The rater or investigator's response choices included: 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; and 7 = among the most extremely ill participants.

Outcome measures

Measure	Brexpiprazole 2 mg n=16 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=12 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score	-0.1 units on a scale Standard Error 0.1	0.0 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 3 (Day 21).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

The severity of illness for each participant was assessed. The rater or investigator's response choices included: 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; and 7 = among the most extremely ill participants.

Outcome measures

Measure	Brexpiprazole 2 mg n=17 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=16 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 3 in CGI-S Score	-0.3 units on a scale Standard Error 0.1	-0.1 units on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 6 (Day 42).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6	3.6 units on a scale Standard Deviation 1.0	3.9 units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 3 (Day 21).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment.

To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).

Outcome measures

Measure	Brexpiprazole 2 mg n=19 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=19 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
CGI-I Score at Week 3	3.7 units on a scale Standard Deviation 0.8	3.8 units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: During trial visits from Day 0 to Week 6 (Day 42).

Population: All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid postbaseline efficacy assessment

A validated clinician-rated scale that measured personal and social functioning in 4 domains: socially useful activities (eg, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment was rated as absent, mild, manifest, marked, severe, or very severe and were converted to a total score on a 100-point scale: 71 to 100 - mild functional difficulty, 31 to 70 - manifest disabilities of various degrees and 1 to 30 - minimal functioning that required intense support and/or supervision.

Outcome measures

Measure	Brexpiprazole 2 mg n=17 Participants Participants received Brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day until week 6 (Day 42)/early termination (ET)	Brexpiprazole 4 mg n=14 Participants Participants received brexpiprazole 1 mg orally per day for 4 days followed by 2 mg per day for 3 days, 3 mg per day for 7 days and 4 mg per day until week 6 (Day 42)/ET.
Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)	1.7 units on a scale Standard Error 1.6	-0.0 units on a scale Standard Error 1.7

Adverse Events

Brexpiprazole 2 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Brexpiprazole 4 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Brexpiprazole 2 mg n=19 participants at risk Brexpiprazole 2 mg/day, once daily dose, tablet, orally Brexpiprazole: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks	Brexpiprazole 4 mg n=19 participants at risk Brexpiprazole 4 mg/day, once daily dose, tablet, orally Brexpiprazole: Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks
Gastrointestinal disorders Abdominal pain upper	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Gastrointestinal disorders Dyspepsia	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Infections and infestations Nasopharyngitis	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Investigations Blood creatine phosphokinase increased	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Investigations Weight increased	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Musculoskeletal and connective tissue disorders Back pain	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Nervous system disorders Akathisia	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Nervous system disorders Extrapyramidal disorder	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Nervous system disorders Headache	15.8% 3/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Nervous system disorders Somnolence	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Psychiatric disorders Agitation	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Psychiatric disorders Anxiety	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Psychiatric disorders Insomnia	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Psychiatric disorders Irritability	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Psychiatric disorders Restlessness	10.5% 2/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Skin and subcutaneous tissue disorders Acne	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention
Skin and subcutaneous tissue disorders Hyperkeratosis	5.3% 1/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention	0.00% 0/19 • Trial visits (Days 0 to 42) An adverse event (AE) was any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug-related. Suspected adverse reaction (AR) - any AE caused by drug; in drug safety reporting, "reasonable possibility" meant to suggest a causal relationship between the drug and the AE. A serious AE (SAE) included any event that resulted in death, life-threatening, inability, hospitalization, congenital anomaly and requirement of medical/surgical intervention

Additional Information

Global Clinical Development

Otsuka Data Transparency Organization

Email: DT-inquiry@otsuka.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60