Trial Outcomes & Findings for Study of the Safety and Efficacy of OPC-34712 as a Complementary Therapy in the Treatment of Adult Attention Deficit/Hyperactivity Disorder (NCT NCT01074294)
NCT ID: NCT01074294
Last Updated: 2023-02-02
Results Overview
The CAARS-O:SV is a 30 items scale with 3 subscales: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Inattentive Symptoms (9 items), DSM- IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The Mixed model repeated measures (MMRM) model was used for analysis.
COMPLETED
PHASE2
740 participants
Baseline [end of Phase A (Week 5)] to Week 11
2023-02-02
Participant Flow
This study was conducted at 37 sites in United States from 16 Mar 2010 to 20 Jun 2011.
The study consisted of a screening phase, phase A (5-week single-blind prospective treatment phase), phase A+ (6-week single-blind phase A responders and non-responders), and phase B (6-week double-blind randomization phase). 740 participants were enrolled in Phase A, and 574 completed Phase A. Of these, 235 incomplete responders then randomized in 2: 1 ratio to Phase B and 339 responders and non-responders continued in Phase A+.
Participant milestones
| Measure |
Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant
Participants received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for 5 weeks. Once assigned to a stimulant by the investigator, participants remained on the same stimulant for the duration of the trial. Participants who met eligibility criteria i.e., who received prior treatment for adult attention deficit/hyperactivity disorder (ADHD) and treatment-naïve participants were included in this arm group. Participants with incomplete response at the end of Phase A (Week 5) entered Phase B and rest of the participants continued to Phase A+.
|
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV {Conners' Adult ADHD Rating Scale-Observer: Screening Version}, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a clinical global impression - improvement scale (CGI-I) score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 milligram (mg) tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant
Participants with response (with a ≥ 30% reduction in ADHD Symptoms Total Score {18 items} between Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, or a CAARS-O:SV ADHD Symptoms Total Score {18 items} of \< 24 at Week 5, or a CGI-I score of \< 3 at Week 5) and non-response (with deterioration or no change in ADHD symptoms at Week 5) at the end of Phase A (Week 5), received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for an additional 6 weeks (up to Week 11).
|
|---|---|---|---|---|
|
Phase A (Day 1 to Week 5)
STARTED
|
740
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
Analyzed for Safety
|
733
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
COMPLETED
|
574
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
NOT COMPLETED
|
166
|
0
|
0
|
0
|
|
Phase B and Phase A+ (Week 6 to Week 11)
STARTED
|
0
|
155
|
80
|
339
|
|
Phase B and Phase A+ (Week 6 to Week 11)
Analyzed for Safety
|
0
|
155
|
80
|
235
|
|
Phase B and Phase A+ (Week 6 to Week 11)
COMPLETED
|
0
|
146
|
70
|
314
|
|
Phase B and Phase A+ (Week 6 to Week 11)
NOT COMPLETED
|
0
|
9
|
10
|
25
|
Reasons for withdrawal
| Measure |
Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant
Participants received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for 5 weeks. Once assigned to a stimulant by the investigator, participants remained on the same stimulant for the duration of the trial. Participants who met eligibility criteria i.e., who received prior treatment for adult attention deficit/hyperactivity disorder (ADHD) and treatment-naïve participants were included in this arm group. Participants with incomplete response at the end of Phase A (Week 5) entered Phase B and rest of the participants continued to Phase A+.
|
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV {Conners' Adult ADHD Rating Scale-Observer: Screening Version}, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a clinical global impression - improvement scale (CGI-I) score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 milligram (mg) tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant
Participants with response (with a ≥ 30% reduction in ADHD Symptoms Total Score {18 items} between Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, or a CAARS-O:SV ADHD Symptoms Total Score {18 items} of \< 24 at Week 5, or a CGI-I score of \< 3 at Week 5) and non-response (with deterioration or no change in ADHD symptoms at Week 5) at the end of Phase A (Week 5), received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for an additional 6 weeks (up to Week 11).
|
|---|---|---|---|---|
|
Phase A (Day 1 to Week 5)
Lost to Follow-up
|
16
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
Adverse Event
|
51
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
Protocol specified withdrawal criteria
|
47
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
Withdrawn From Participation by the Investigator
|
3
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
Withdrawal by Subject
|
32
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
Protocol deviation
|
10
|
0
|
0
|
0
|
|
Phase A (Day 1 to Week 5)
Participants not Dosed
|
7
|
0
|
0
|
0
|
|
Phase B and Phase A+ (Week 6 to Week 11)
Lost to Follow-up
|
0
|
2
|
2
|
11
|
|
Phase B and Phase A+ (Week 6 to Week 11)
Adverse Event
|
0
|
2
|
3
|
8
|
|
Phase B and Phase A+ (Week 6 to Week 11)
Protocol-Specified Withdrawal Criteria
|
0
|
2
|
0
|
0
|
|
Phase B and Phase A+ (Week 6 to Week 11)
Withdrawal by Subject
|
0
|
2
|
2
|
4
|
|
Phase B and Phase A+ (Week 6 to Week 11)
Protocol Violation
|
0
|
0
|
3
|
2
|
|
Phase B and Phase A+ (Week 6 to Week 11)
Lack of Efficacy
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. Phase A+ Sample- all non-randomized participants who were Phase A Responders or Phase A Non-responders, and continued on Stimulant + single-blind placebo beyond Week 5. Number analyzed is the number of participants with data available for analyses at Baseline.
Baseline characteristics by cohort
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=155 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=80 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant
n=339 Participants
Participants with response (with a ≥ 30% reduction in ADHD Symptoms Total Score {18 items} between Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, or a CAARS-O:SV ADHD Symptoms Total Score {18 items} of \< 24 at Week 5, or a CGI-I score of \< 3 at Week 5) and non-response (with deterioration or no change in ADHD symptoms at Week 5) at the end of Phase A (Week 5), received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for an additional 6 weeks (up to Week 11).
|
Total
n=574 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
36.0 years
n=155 Participants
|
33.6 years
n=80 Participants
|
33.6 years
n=339 Participants
|
34.4 years
n=574 Participants
|
|
Sex: Female, Male
Female
|
79 Participants
n=155 Participants
|
38 Participants
n=80 Participants
|
164 Participants
n=339 Participants
|
281 Participants
n=574 Participants
|
|
Sex: Female, Male
Male
|
76 Participants
n=155 Participants
|
42 Participants
n=80 Participants
|
175 Participants
n=339 Participants
|
293 Participants
n=574 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
19 Participants
n=155 Participants
|
10 Participants
n=80 Participants
|
48 Participants
n=339 Participants
|
77 Participants
n=574 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
136 Participants
n=155 Participants
|
69 Participants
n=80 Participants
|
288 Participants
n=339 Participants
|
493 Participants
n=574 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=155 Participants
|
1 Participants
n=80 Participants
|
3 Participants
n=339 Participants
|
4 Participants
n=574 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=155 Participants
|
1 Participants
n=80 Participants
|
4 Participants
n=339 Participants
|
6 Participants
n=574 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=155 Participants
|
0 Participants
n=80 Participants
|
9 Participants
n=339 Participants
|
12 Participants
n=574 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=155 Participants
|
0 Participants
n=80 Participants
|
0 Participants
n=339 Participants
|
0 Participants
n=574 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=155 Participants
|
10 Participants
n=80 Participants
|
38 Participants
n=339 Participants
|
57 Participants
n=574 Participants
|
|
Race (NIH/OMB)
White
|
140 Participants
n=155 Participants
|
65 Participants
n=80 Participants
|
281 Participants
n=339 Participants
|
486 Participants
n=574 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=155 Participants
|
0 Participants
n=80 Participants
|
0 Participants
n=339 Participants
|
0 Participants
n=574 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=155 Participants
|
4 Participants
n=80 Participants
|
7 Participants
n=339 Participants
|
13 Participants
n=574 Participants
|
|
CAARS-O:SV ADHD Symptoms Total Score (18 items)
|
32.94 score on a scale
n=153 Participants • Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. Phase A+ Sample- all non-randomized participants who were Phase A Responders or Phase A Non-responders, and continued on Stimulant + single-blind placebo beyond Week 5. Number analyzed is the number of participants with data available for analyses at Baseline.
|
33.99 score on a scale
n=78 Participants • Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. Phase A+ Sample- all non-randomized participants who were Phase A Responders or Phase A Non-responders, and continued on Stimulant + single-blind placebo beyond Week 5. Number analyzed is the number of participants with data available for analyses at Baseline.
|
40.1 score on a scale
n=339 Participants • Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. Phase A+ Sample- all non-randomized participants who were Phase A Responders or Phase A Non-responders, and continued on Stimulant + single-blind placebo beyond Week 5. Number analyzed is the number of participants with data available for analyses at Baseline.
|
35.67 score on a scale
n=570 Participants • Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. Phase A+ Sample- all non-randomized participants who were Phase A Responders or Phase A Non-responders, and continued on Stimulant + single-blind placebo beyond Week 5. Number analyzed is the number of participants with data available for analyses at Baseline.
|
PRIMARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
The CAARS-O:SV is a 30 items scale with 3 subscales: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Inattentive Symptoms (9 items), DSM- IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The Mixed model repeated measures (MMRM) model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=147 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=69 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Mean Change From Baseline (End of Phase A) in the CAARS-O:SV ADHD Symptoms Total Score (18 Items) to End of Phase B
|
-9.02 score on a scale
Standard Error 0.77
|
-9.71 score on a scale
Standard Error 1.06
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
WRAADDS is used to measure the severity of symptoms in adults with ADHD. This structured interview consists of 28 items in 7 psychopathologic domains, which were rated by a clinical expert on a 0 to 2-point Likert scale. The psychopathologic 7 domains are inattention (6 items), impulsivity (3 items), and hyperactivity (3 items), disorganization (5 items), temper (3 items), affective lability (4 items), and emotional over-reactivity (4 items). The scale rated individual items from 0 to 2 (0=not present, 1=mild, 2=clearly present) and summarized each of the 7 categories on a 0-to-4 scale (0=none, 1=mild, 2=moderate, 3=quite a bit, 4=very much). The WRAADDS total score is defined as sum of all 28 item sub scores (range 0 - 56), higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The analysis of covariance (ANCOVA) method was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=150 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=74 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) Total Score to End of Phase B
|
-3.93 score on a scale
Standard Error 0.42
|
-3.84 score on a scale
Standard Error 0.56
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
The ISI is self-report instrument that has been validated specifically for measuring the perceived severity of insomnia. The scale was composed of a total of 7 items based on self-report questionnaire based on several indicators assessing the perceived severity of difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item was rated on a scale from 0 (none) to 4 (higher score indicating greater impairment/concern). A total score ranging from 0 to 28 was calculated from the sum of the individual item scores, higher scores indicate increased severity of insomnia. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=147 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=69 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in Sleep Improvement Measured by Insomnia Severity Index (ISI) Total Score to End of Phase B
|
-1.05 score on a scale
Standard Error 0.41
|
-1.62 score on a scale
Standard Error 0.56
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
The ISI is self-report instrument that has been validated specifically for measuring the perceived severity of insomnia. The scale was composed of a total of 7 items based on self-report questionnaire based on several indicators assessing the perceived severity of difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item was rated on a scale from 0 (none) to 4 (higher score indicating greater impairment/concern). A total score ranging from 0 to 28 was calculated from the sum of the individual item scores, higher scores indicate increased severity of insomnia. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=147 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=69 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in Sleep Improvement Measured by ISI for Item 2 Score (Difficulty Staying Asleep) to End of Phase B
|
-0.04 score on a scale
Standard Error 0.08
|
-0.37 score on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
ADHD was measured with the CANTAB. SWM test was one of the tasks of CANTAB, SWM measured the ability to retain spatial information and to manipulate remembered items in working memory. This test was sensitive measure of executive dysfunction. Participants search for colored tokens hidden inside boxes on screen by touching them. The critical instruction was that once token has been found inside box, no token was hidden inside that box again, so participants must not return to box where a token was found. The key measurement of the SWM task is the SWM Between Errors 4-8 Boxes, which measured the total number of times a participant revisits a box in which a token has previously been found is measured for the 4, 6, and 8-box stages. Total scores ranged from 0-153. A lower score indicated better performance. The ANCOVA model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in the Spatial Working Memory (SWM) Between Errors 4-8 Boxes Test Score as Measured by Cambridge Neuropsychological Test Automated Battery (CANTAB) to End of Phase B
|
0.10 score on a scale
Standard Error 0.67
|
-0.31 score on a scale
Standard Error 0.90
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Weeks 6, 7, 8, 9 and 10Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The CAARS-O:SV is a 30 items scale with 3 subscales DSM-IV Inattentive Symptoms (9 items), DSM-IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11
Change at Week 6
|
-3.82 score on a scale
Standard Error 0.49
|
-4.62 score on a scale
Standard Error 0.64
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11
Change at Week 7
|
-5.54 score on a scale
Standard Error 0.58
|
-6.21 score on a scale
Standard Error 0.78
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11
Change at Week 8
|
-6.37 score on a scale
Standard Error 0.68
|
-6.99 score on a scale
Standard Error 0.92
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11
Change at Week 9
|
-7.58 score on a scale
Standard Error 0.71
|
-8.14 score on a scale
Standard Error 0.96
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11
Change at Week 10
|
-7.71 score on a scale
Standard Error 0.76
|
-9.11 score on a scale
Standard Error 1.04
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
The CAARS-O:SV is a 30 items scale with 3 subscales DSM-IV Inattentive Symptoms (9 items), DSM-IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). The inattentive symptoms subscale (9 items) is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 27, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 8
|
-3.14 score on a scale
Standard Error 0.40
|
-3.42 score on a scale
Standard Error 0.54
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 9
|
-3.74 score on a scale
Standard Error 0.42
|
-4.04 score on a scale
Standard Error 0.57
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 6
|
-2.00 score on a scale
Standard Error 0.32
|
-2.43 score on a scale
Standard Error 0.41
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 7
|
-2.94 score on a scale
Standard Error 0.36
|
-3.20 score on a scale
Standard Error 0.48
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 10
|
-3.95 score on a scale
Standard Error 0.45
|
-4.85 score on a scale
Standard Error 0.62
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 11
|
-4.58 score on a scale
Standard Error 0.44
|
-4.86 score on a scale
Standard Error 0.60
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The CAARS-O:SV is a 30 items scale with 3 subscales DSM-IV Inattentive Symptoms (9 items), DSM-IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). The hyperactive/impulsive Symptoms Subscale is (9 items) scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 27, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 10
|
-3.83 score on a scale
Standard Error 0.41
|
-4.17 score on a scale
Standard Error 0.55
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 6
|
-1.88 score on a scale
Standard Error 0.29
|
-2.11 score on a scale
Standard Error 0.38
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 7
|
-2.66 score on a scale
Standard Error 0.32
|
-2.94 score on a scale
Standard Error 0.43
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 8
|
-3.29 score on a scale
Standard Error 0.36
|
-3.48 score on a scale
Standard Error 0.49
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 9
|
-3.90 score on a scale
Standard Error 0.39
|
-4.01 score on a scale
Standard Error 0.53
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B
Change at Week 11
|
-4.51 score on a scale
Standard Error 0.42
|
-4.80 score on a scale
Standard Error 0.58
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). The ADHD index score (12 items) is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 36, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B
Change at Week 6
|
-2.06 score on a scale
Standard Error 0.34
|
-2.20 score on a scale
Standard Error 0.44
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B
Change at Week 7
|
-3.47 score on a scale
Standard Error 0.41
|
-3.38 score on a scale
Standard Error 0.55
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B
Change at Week 8
|
-4.01 score on a scale
Standard Error 0.44
|
-3.80 score on a scale
Standard Error 0.59
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B
Change at Week 9
|
-4.32 score on a scale
Standard Error 0.46
|
-4.78 score on a scale
Standard Error 0.62
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B
Change at Week 10
|
-4.65 score on a scale
Standard Error 0.47
|
-5.23 score on a scale
Standard Error 0.64
|
|
Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B
Change at Week 11
|
-5.60 score on a scale
Standard Error 0.48
|
-5.94 score on a scale
Standard Error 0.66
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 7 and 9Population: Efficacy Sample=participants in Randomized Sample who had Baseline value for Phase B (ie Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As prespecified in protocol, SAP data is reported only for Phase B participants. Overall number of participants=number of participants with data available for analyses at Baseline. Number analyzed=number of participants with data available for analyses at given timepoint.
The ISI is self-report instrument that has been validated specifically for measuring the perceived severity of insomnia. The scale was composed of a total of 7 items based on self-report questionnaire based on several indicators assessing the perceived severity of difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item was rated on a scale from 0 (none) to 4 (higher score indicating greater impairment/concern). A total score ranging from 0 to 28 was calculated from the sum of the individual item scores, higher scores indicate increased severity of insomnia. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=150 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=77 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) to Weeks 7 and 9 in ISI Total Score
Change at Week 7
|
-0.81 score on a scale
Standard Error 0.33
|
-0.83 score on a scale
Standard Error 0.44
|
|
Change From Baseline (End of Phase A) to Weeks 7 and 9 in ISI Total Score
Change at Week 9
|
-0.99 score on a scale
Standard Error 0.37
|
-1.48 score on a scale
Standard Error 0.49
|
SECONDARY outcome
Timeframe: Baseline [(end of Phase A (Week 5)] to Weeks 7, 9 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The ISI is self-report instrument that has been validated specifically for measuring the perceived severity of insomnia. The scale was composed of a total of 7 items based on self-report questionnaire based on several indicators assessing the perceived severity. difficulties initiating sleep, staying asleep, and early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Each item was rated on a scale from 0 (none) to 4 (higher score indicating greater impairment/concern). A negative change from Baseline indicates improvement. The Cochran-Mantel-Haenszel model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Difficulty Falling Asleep: Week 7
|
33.6 percentage of participants
|
32.4 percentage of participants
|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Difficulty Falling Asleep: Week 9
|
33.3 percentage of participants
|
37.7 percentage of participants
|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Difficulty Falling Asleep: Week 11
|
35.3 percentage of participants
|
39.0 percentage of participants
|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Difficulty Staying Asleep: Week 7
|
26.8 percentage of participants
|
35.1 percentage of participants
|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Difficulty Staying Asleep: Week 9
|
25.3 percentage of participants
|
33.8 percentage of participants
|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Difficulty Staying Asleep: Week 11
|
24.7 percentage of participants
|
37.7 percentage of participants
|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Waking Up Too Early: Week 7
|
28.2 percentage of participants
|
25.7 percentage of participants
|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Waking Up Too Early: Week 9
|
30.7 percentage of participants
|
26.0 percentage of participants
|
|
Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B
Waking Up Too Early: Week 11
|
29.3 percentage of participants
|
28.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The CAARS-S:SV is a self-reported 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B
Change at Week 6
|
-1.75 score on a scale
Standard Error 0.58
|
-2.16 score on a scale
Standard Error 0.75
|
|
Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B
Change at Week 7
|
-3.01 score on a scale
Standard Error 0.65
|
-3.47 score on a scale
Standard Error 0.87
|
|
Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B
Change at Week 8
|
-4.15 score on a scale
Standard Error 0.68
|
-4.08 score on a scale
Standard Error 0.92
|
|
Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B
Change at Week 9
|
-4.24 score on a scale
Standard Error 0.73
|
-5.23 score on a scale
Standard Error 0.99
|
|
Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B
Change at Week 10
|
-4.63 score on a scale
Standard Error 0.77
|
-6.11 score on a scale
Standard Error 1.04
|
|
Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B
Change at Week 11
|
-5.38 score on a scale
Standard Error 0.78
|
-6.33 score on a scale
Standard Error 1.07
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The CAARS-S:SV is a self-reported 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). The Inattentive Symptoms Subscale is (9 items) scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 27, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 6
|
-0.87 score on a scale
Standard Error 0.33
|
-1.16 score on a scale
Standard Error 0.43
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 7
|
-1.64 score on a scale
Standard Error 0.37
|
-1.62 score on a scale
Standard Error 0.49
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 8
|
-2.08 score on a scale
Standard Error 0.40
|
-1.93 score on a scale
Standard Error 0.54
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 9
|
-2.08 score on a scale
Standard Error 0.42
|
-2.42 score on a scale
Standard Error 0.56
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 10
|
-2.43 score on a scale
Standard Error 0.43
|
-2.84 score on a scale
Standard Error 0.58
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 11
|
-2.54 score on a scale
Standard Error 0.43
|
-3.10 score on a scale
Standard Error 0.59
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). The Hyperactive/Impulsive Symptoms Subscale is (9 items) scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 27, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 6
|
-0.91 score on a scale
Standard Error 0.32
|
-1.06 score on a scale
Standard Error 0.41
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 7
|
-1.38 score on a scale
Standard Error 0.35
|
-1.88 score on a scale
Standard Error 0.47
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 8
|
-2.09 score on a scale
Standard Error 0.36
|
-2.20 score on a scale
Standard Error 0.47
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 9
|
-2.18 score on a scale
Standard Error 0.39
|
-2.87 score on a scale
Standard Error 0.52
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 10
|
-2.21 score on a scale
Standard Error 0.41
|
-3.33 score on a scale
Standard Error 0.55
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B
Change at Week 11
|
-2.86 score on a scale
Standard Error 0.42
|
-3.31 score on a scale
Standard Error 0.57
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). The ADHD Index Subscale is (12 items) scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) with total score ranging from 0 to 36, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B
Change at Week 6
|
-1.09 score on a scale
Standard Error 0.37
|
-1.16 score on a scale
Standard Error 0.48
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B
Change at Week 7
|
-1.86 score on a scale
Standard Error 0.42
|
-2.13 score on a scale
Standard Error 0.55
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B
Change at Week 8
|
-2.69 score on a scale
Standard Error 0.44
|
-2.43 score on a scale
Standard Error 0.59
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B
Change at Week 9
|
-3.07 score on a scale
Standard Error 0.46
|
-3.00 score on a scale
Standard Error 0.61
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B
Change at Week 10
|
-3.42 score on a scale
Standard Error 0.47
|
-3.56 score on a scale
Standard Error 0.63
|
|
Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B
Change at Week 11
|
-4.05 score on a scale
Standard Error 0.48
|
-3.90 score on a scale
Standard Error 0.65
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Number analyzed is the number of participants with data available for analyses at the given time-point.
The CGI-S is performed to rate the severity of a participant's condition on an 8-point scale ranging from 0 to 7 where 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. A negative change from Baseline indicates improvement. The MMRM model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B
Change at Week 6
|
-0.75 score on a scale
Standard Error 0.06
|
-0.71 score on a scale
Standard Error 0.08
|
|
Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B
Change at Week 7
|
-0.92 score on a scale
Standard Error 0.07
|
-0.88 score on a scale
Standard Error 0.09
|
|
Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B
Change at Week 8
|
-1.03 score on a scale
Standard Error 0.07
|
-0.97 score on a scale
Standard Error 0.10
|
|
Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B
Change at Week 9
|
-1.16 score on a scale
Standard Error 0.08
|
-1.10 score on a scale
Standard Error 0.11
|
|
Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B
Change at Week 10
|
-1.17 score on a scale
Standard Error 0.08
|
-1.28 score on a scale
Standard Error 0.11
|
|
Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B
Change at Week 11
|
-1.31 score on a scale
Standard Error 0.09
|
-1.37 score on a scale
Standard Error 0.12
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
The SWM test assesses the cognitive domain of executive function (high-level thinking and decision making). SWM task was SWM Strategy 6-8 Boxes, in which the total number of distinct boxes used by the participant to begin a new search for a token within the same problem was measured for the 6- and 8-box stages. The SWM strategy index of executive function represented the number of times a participant began a search with a different box. Participant was asked to find tokens in on-screen boxes and move them. Difficulty ranged from 4 to 8 box assessments. Strategy score was the number of unique boxes the participant searched in 6 and 8 box trials. 6 box trial scores ranged from 1 (1 box searched for all 6 tokens) to 6 (6 boxes searched for 6 tokens). 8 box trial score ranged from 1 (1 box searched) to 8 (8 boxes searched for 8 tokens). Total of the 2 trial scores ranged from 2 to 14. A lower score reflects better performance. The ANCOVA method was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in the SWM Strategy 6-8 Boxes Test Score as Measured by CANTAB to End of Phase B
|
0.15 score on a scale
Standard Error 0.21
|
-0.12 score on a scale
Standard Error 0.28
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
Assessments were performed with CANTAB. SWM test assesses cognitive domain of executive function (high-level thinking and decision making). Participants search for colored tokens hidden inside boxes on screen by touching them. Critical instruction is that once a token has been found inside a box, there was never be a token hidden inside that box again, so participants must not return to a box where a token has been found. Within Errors 4-8 Boxes, which measured number of times a participant revisited a box that had already been found to be empty during the same search. Value was reported as total number of errors for 4-, 6-, and 8-box stages. Observed range for Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant is -8.00 to 6.00 (change from baseline) and for Phase B (Double-blind Randomization Phase): Placebo + Stimulant is -10.0 to 23.00 (change from baseline). A lower score reflects better performance. LOCF method was used to impute missing data.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in the SWM Within Errors 4-8 Boxes Test Score as Measured by CANTAB to End of Phase B
|
0.00 score on a scale
Standard Error 0.16
|
0.30 score on a scale
Standard Error 0.22
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
Assessments were performed with the CANTAB. The RVP task tested continuous performance and visual sustained attention. In the center of the computer screen, digits from 2 to 9 appear inside a white box in pseudorandom order at a rate of 100 digits per minute. Participants must touch the press pad when they detect a series of target digit sequences (eg, 2-4-6, 4-6-8, 3-5-7) which appeared at a rate of 9 sequences every 100 numbers. Data from the RVP task were summarized in 3 ways: RVP A prime, RVP median response latency, and RVP total false alarms. RVP A prime was the signal detection measure of sensitivity to the target, regardless of response tendency (range 0.00 to 1.00; bad to good). In essence, this metric was a measure of how good the participant was at detecting target sequences. Higher scores indicated better performance. The ANCOVA method was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in the Rapid Visual Information Processing (RVP) A Prime Test Score as Measured by CANTAB to End of Phase B
|
0.00 score on a scale
Standard Error 0.00
|
0.01 score on a scale
Standard Error 0.00
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
Assessments were performed with CANTAB. RVP task tested continuous performance and visual sustained attention. In the center of computer screen, digits from 2 to 9 appear inside white box in pseudorandom order at a rate of 100 digits per minute. Participants must touch press pad when they detect a series of target digit sequences (eg, 2-4-6, 4-6-8, 3-5-7) which appeared at a rate of 9 sequences every 100 numbers. Data from RVP task were summarized in 3 ways: RVP A prime, RVP median response latency, and RVP total false alarms. Median response latency was measured during the assessed part of test (7-minute continuous part of test after initial 2 minutes training phase). Observed range for Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant is -338 to 282.0 (change from baseline) and for Phase B (Double-blind Randomization Phase): Placebo + Stimulant is -134 to 235.0 (change from baseline). Lower scores indicate better performance. ANCOVA method was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in the RVP Median Response Latency Score as Measured by CANTAB to End of Phase B
|
-17.1 score on a scale
Standard Error 5.36
|
-2.89 score on a scale
Standard Error 7.10
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
RVP task tested continuous performance and visual sustained attention. In center of computer screen, digits from 2- 9 appear inside a white box in pseudorandom order at a rate of 100 digits per minute. Participants must touch press pad when they detect a series of target digit sequences (e.g., 2-4-6, 4-6-8, 3-5-7) which appeared at a rate of 9 sequences every 100 numbers. Data from RVP task were summarized in 3 ways: RVP A prime, RVP median response latency, and RVP total false alarms. False alarms were determined from number of times that participants responded outside response window of a target sequence during assessed part of test. Observed range for Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant is -26.0 to 13.00 (change from baseline) and for Phase B (Double-blind Randomization Phase): Placebo + Stimulant is -25.0 to 144.0 (change from baseline). Lower scores indicate better performance. ANCOVA model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in RVP Total False Alarms Score as Measured by CANTAB to End of Phase B
|
0.12 score on a scale
Standard Error 1.01
|
0.58 score on a scale
Standard Error 1.34
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
In SST, an arrow pointing either left or right is displayed on computer screen. Participant responded to arrow by pressing corresponding button (i.e., left or right) on press pad. If an audio tone is presented when arrow is displayed, participant inhibited response. Proportion of successful stops, and median reaction time on Go trials was measured. SST SSRT was an estimate of length of time between go stimulus and stop stimulus at which participant was able to successfully inhibit response on 50% of trials and calculated from SST reaction time on Go trials measure and SST stop signal delay (SSD) 50% measure as \[reaction time on Go trials\] - \[SSD (50%)\], where SSD (50%) measure was calculated as arithmetic mean of measured SSD, or failed stop reaction time, from completed assessment stop trials. Observed change from baseline range for Phase B: Brexpiprazole + Stimulant: -204 to 237.0 and for Phase B: Placebo + Stimulant: -176 to 113.0. Lower scores indicate better performance.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in the Stop Signal Task (SST) Stop Signal Reaction Time (SSRT) Score as Measured by CANTAB to End of Phase B
|
13.41 score on a scale
Standard Error 5.12
|
-4.10 score on a scale
Standard Error 6.92
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
SST measures participants ability to inhibit a response. An arrow pointing either left or right is displayed on computer screen. Participant responded to arrow by pressing corresponding button (i.e., left or right) on press pad. If an audio tone is presented when arrow is displayed, participant inhibited his/her response. Proportion of successful stops, and median reaction time on Go trials was measured. The proportion of successful stops is calculated as the number of times that the participant stopped successfully, divided by the total number of stop signals. Observed range for Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant: -0.40 to 0.40 (change from baseline) and for Phase B (Double-blind Randomization Phase): Placebo + Stimulant: -0.38 to 0.38 (change from baseline). Higher scores indicate a positive outcome for proportion of successful stops.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in the SST Proportion of Successful Stops Score as Measured by CANTAB to End of Phase B
|
-0.01 score on a scale
Standard Error 0.01
|
0.01 score on a scale
Standard Error 0.01
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
SST measures participants ability to inhibit a response. An arrow pointing either left or right is displayed on computer screen. Participant responded to arrow by pressing corresponding button (i.e., left or right) on press pad. If an audio tone is presented when arrow is displayed, participant inhibited his/her response. Proportion of successful stops, and median reaction time on Go trials was measured. The median reaction time on Go trials is the median of the reaction time assessed on Go trials to which the participant responded correctly. Observed range for Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant: -277 to 266.0 (change from baseline) and for Phase B (Double-blind Randomization Phase): Placebo + Stimulant: -462 to 358.0 (change from baseline). Lower scores indicate better performance.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=145 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=72 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in SST Median Reaction Time Score on Go Trials as Measured by CANTAB to End of Phase B
|
-6.70 score on a scale
Standard Error 8.39
|
-1.03 score on a scale
Standard Error 11.2
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
WRAADDS is used to measure the severity of symptoms in adults with ADHD. This structured interview consists of 28 items in 7 psychopathologic domains, which were rated by a clinical expert on a 0 to 2-point Likert scale. The psychopathologic 7 domains are inattention (6 items), impulsivity (3 items), and hyperactivity (3 items), disorganization (5 items), temper (3 items), affective lability (4 items), and emotional over-reactivity (4 items). The scale rated individual items from 0 to 2 (0=not present, 1=mild, 2=clearly present). The score for attention + organization subscale score ranges from 0-22, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The ANCOVA method was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=150 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=74 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in WRAADDS Attention + Organization Subscale Score to End of Phase B
|
-1.47 score on a scale
Standard Error 0.17
|
-1.42 score on a scale
Standard Error 0.22
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
WRAADDS is used to measure the severity of symptoms in adults with ADHD. This structured interview consists of 28 items in 7 psychopathologic domains, which were rated by a clinical expert on a 0 to 2-point Likert scale. The psychopathologic 7 domains are inattention (6 items), impulsivity (3 items), and hyperactivity (3 items), disorganization (5 items), temper (3 items), affective lability (4 items), and emotional over-reactivity (4 items). The scale rated individual items from 0 to 2 (0=not present, 1=mild, 2=clearly present). The score for hyperactivity + impulsivity subscale score ranges from 0-12, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The ANCOVA model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=150 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=74 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From End of Phase A (Week 5 Visit) to End of Phase B (Week 11 Visit) in WRAADDS Hyperactivity + Impulsivity Subscale Score to End of Phase B
|
-1.27 score on a scale
Standard Error 0.14
|
-1.01 score on a scale
Standard Error 0.19
|
SECONDARY outcome
Timeframe: Baseline [end of Phase A (Week 5)] to Week 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants. Overall number analyzed is the number of participants available for analyses.
WRAADDS is used to measure the severity of symptoms in adults with ADHD. This structured interview consists of 28 items in 7 psychopathologic domains, which were rated by a clinical expert on a 0 to 2-point Likert scale. The psychopathologic 7 domains are inattention (6 items), impulsivity (3 items), and hyperactivity (3 items), disorganization (5 items), temper (3 items), affective lability (4 items), and emotional over-reactivity (4 items). The scale rated individual items from 0 to 2 (0=not present, 1=mild, 2=clearly present). The score for temper + mood Lability + emotional over-reactivity subscale score ranges from 0-22, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The ANCOVA model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=150 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=74 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Change From Baseline (End of Phase A) in WRAADDS Temper + Mood Lability + Emotional Over-reactivity Subscale Score to End of Phase B
|
-1.24 score on a scale
Standard Error 0.20
|
-1.35 score on a scale
Standard Error 0.26
|
SECONDARY outcome
Timeframe: Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants.
The CGI-I permits a global evaluation of the participant's improvement over time. The CGI-I is a 8-point scale ranging from 0 to 7 where 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 CGI-I is completed by the clinician and assesses the participant's improvement relative to the symptoms at Baseline. The Cochran-Mantel-Haenszel model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Mean CGI-I Score at Each Timepoint in Phase B
Week 6
|
3.19 score on a scale
Standard Deviation 0.81
|
3.12 score on a scale
Standard Deviation 0.77
|
|
Mean CGI-I Score at Each Timepoint in Phase B
Week 7
|
3.04 score on a scale
Standard Deviation 0.88
|
3.08 score on a scale
Standard Deviation 0.80
|
|
Mean CGI-I Score at Each Timepoint in Phase B
Week 8
|
2.93 score on a scale
Standard Deviation 0.96
|
2.88 score on a scale
Standard Deviation 1.01
|
|
Mean CGI-I Score at Each Timepoint in Phase B
Week 9
|
2.82 score on a scale
Standard Deviation 1.02
|
2.81 score on a scale
Standard Deviation 1.03
|
|
Mean CGI-I Score at Each Timepoint in Phase B
Week 10
|
2.80 score on a scale
Standard Deviation 0.99
|
2.76 score on a scale
Standard Deviation 1.07
|
|
Mean CGI-I Score at Each Timepoint in Phase B
Week 11
|
2.68 score on a scale
Standard Deviation 1.06
|
2.69 score on a scale
Standard Deviation 1.17
|
SECONDARY outcome
Timeframe: Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants.
Response was defined as ≥ 30% reduction in CAARS-O:SV ADHD Symptoms Total Score (18 items) from end of Phase A (Week 5 visit). An 18-item ADHD Symptoms Total Score consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales. The CAARS-O:SV was designed to measure a cross-section of ADHD-related symptoms and behaviors in adults using observer and self-report scales. Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B
Week 10
|
37.9 percentage of participants
|
44.9 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B
Week 6
|
15.0 percentage of participants
|
12.8 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B
Week 7
|
24.2 percentage of participants
|
24.4 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B
Week 8
|
28.8 percentage of participants
|
33.3 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B
Week 9
|
35.9 percentage of participants
|
41.0 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B
Week 11
|
45.1 percentage of participants
|
50.0 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants.
Remission was defined as CAARS-O:SV ADHD Symptoms Total Score (18 items) of ≤ 18 and a ≥ 30% reduction in CAARS-O:SV ADHD Symptoms Total Score (18 items) from end of Phase A (Week 5 visit). An 18-item ADHD Symptoms Total Score consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales. The CAARS-O:SV was designed to measure a cross-section of ADHD-related symptoms and behaviors in adults using observer and self-report scales. Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. The Cochran-Mantel-Haenszel model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B
Week 6
|
7.19 percentage of participants
|
6.41 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B
Week 7
|
12.4 percentage of participants
|
12.8 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B
Week 8
|
19.0 percentage of participants
|
19.2 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B
Week 9
|
20.9 percentage of participants
|
23.1 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B
Week 10
|
25.5 percentage of participants
|
28.2 percentage of participants
|
|
Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B
Week 11
|
27.5 percentage of participants
|
33.3 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants.
Response was defined as ≥ 30% reduction in CAARS-S:SV ADHD Symptoms Total Score (18 items) from end of Phase A (Week 5 visit). The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. The Cochran-Mantel-Haenszel model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B
Week 6
|
11.8 percentage of participants
|
12.8 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B
Week 7
|
18.3 percentage of participants
|
15.4 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B
Week 8
|
21.6 percentage of participants
|
21.8 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B
Week 9
|
29.4 percentage of participants
|
29.5 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B
Week 10
|
25.5 percentage of participants
|
32.1 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B
Week 11
|
31.4 percentage of participants
|
37.2 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants.
Remission was defined as CAARS-S:SV ADHD Symptoms Total Score (18 items) of ≤ 18 and a ≥ 30% reduction in CAARS-S:SV ADHD Symptoms Total Score (18 items) from end of Phase A (Week 5 visit). The CAARS-S:SV is a 30 items scale with 3 subscales inattention (9 items), hyperactivity-impulsivity (9 items), and ADHD index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the Inattentive Symptoms and Hyperactive/Impulsive Symptoms subscales is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. The Cochran-Mantel-Haenszel model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B
Week 6
|
8.50 percentage of participants
|
7.69 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B
Week 7
|
12.4 percentage of participants
|
12.8 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B
Week 8
|
15.7 percentage of participants
|
15.4 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B
Week 9
|
20.9 percentage of participants
|
20.5 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B
Week 10
|
20.9 percentage of participants
|
19.2 percentage of participants
|
|
Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B
Week 11
|
24.2 percentage of participants
|
25.6 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 6, 7, 8, 9, 10 and 11Population: Efficacy Sample consisted of participants in the Randomized Sample who had a Baseline value for Phase B (ie, Week 5) and at least one post-randomization efficacy evaluation for CAARS-O:SV ADHD symptoms Total Score (18 items) in Phase B. As pre-specified in the protocol and SAP the data is reported only for Phase B participants.
Response was defined as a CGI-I score of 1 or 2 (very much improved or much improved). The CGI-I permits a global evaluation of the participant's improvement over time. The CGI-I is a 8-point scale ranging from 0 to 7 where 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 Cochran-Mantel-Haenszel model was used for analysis.
Outcome measures
| Measure |
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=153 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=78 Participants
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
|---|---|---|
|
Percentage of Participants With CGI-I Response Rate in Phase B
Week 6
|
18.3 percentage of participants
|
15.4 percentage of participants
|
|
Percentage of Participants With CGI-I Response Rate in Phase B
Week 7
|
23.5 percentage of participants
|
17.9 percentage of participants
|
|
Percentage of Participants With CGI-I Response Rate in Phase B
Week 8
|
31.4 percentage of participants
|
30.8 percentage of participants
|
|
Percentage of Participants With CGI-I Response Rate in Phase B
Week 9
|
37.9 percentage of participants
|
41.0 percentage of participants
|
|
Percentage of Participants With CGI-I Response Rate in Phase B
Week 10
|
40.5 percentage of participants
|
39.7 percentage of participants
|
|
Percentage of Participants With CGI-I Response Rate in Phase B
Week 11
|
44.4 percentage of participants
|
44.9 percentage of participants
|
Adverse Events
Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant
Serious adverse events
| Measure |
Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant
n=733 participants at risk
Participants received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for 5 weeks. Once assigned to a stimulant by the investigator, participants remained on the same stimulant for the duration of the trial. Participants who met eligibility criteria i.e., who received prior treatment for adult ADHD and treatment-naïve participants were included in this arm group. Participants with incomplete response at the end of Phase A (Week 5) entered Phase B and rest of the participants continued to Phase A+.
|
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=155 participants at risk
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV {Conners' Adult ADHD Rating Scale-Observer: Screening Version}, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=80 participants at risk
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant
n=339 participants at risk
Participants with response (with a ≥ 30% reduction in ADHD Symptoms Total Score {18 items} between Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, or a CAARS-O:SV ADHD Symptoms Total Score {18 items} of \< 24 at Week 5, or a CGI-I score of \< 3 at Week 5) and non-response (with deterioration or no change in ADHD symptoms at Week 5) at the end of Phase A (Week 5), received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for an additional 6 weeks (up to Week 11).
|
|---|---|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
1.2%
1/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
1.2%
1/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
Other adverse events
| Measure |
Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant
n=733 participants at risk
Participants received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for 5 weeks. Once assigned to a stimulant by the investigator, participants remained on the same stimulant for the duration of the trial. Participants who met eligibility criteria i.e., who received prior treatment for adult ADHD and treatment-naïve participants were included in this arm group. Participants with incomplete response at the end of Phase A (Week 5) entered Phase B and rest of the participants continued to Phase A+.
|
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
n=155 participants at risk
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV {Conners' Adult ADHD Rating Scale-Observer: Screening Version}, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2mg tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
n=80 participants at risk
Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
|
Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant
n=339 participants at risk
Participants with response (with a ≥ 30% reduction in ADHD Symptoms Total Score {18 items} between Baseline of Phase A and the end of prospective treatment {Week 5} as measured by the CAARS-O:SV, or a CAARS-O:SV ADHD Symptoms Total Score {18 items} of \< 24 at Week 5, or a CGI-I score of \< 3 at Week 5) and non-response (with deterioration or no change in ADHD symptoms at Week 5) at the end of Phase A (Week 5), received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for an additional 6 weeks (up to Week 11).
|
|---|---|---|---|---|
|
Psychiatric disorders
Insomnia
|
0.00%
0/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
8.4%
13/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
1.2%
1/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
5.0%
17/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
1.9%
3/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
6.2%
5/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
3.2%
5/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
6.2%
5/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Investigations
Weight decreased
|
6.4%
47/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
3.2%
5/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
7.5%
6/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Nervous system disorders
Headache
|
17.5%
128/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
7.1%
11/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
12.5%
10/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Gastrointestinal disorders
Dry Mouth
|
15.4%
113/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Gastrointestinal disorders
Nausea
|
7.0%
51/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
General disorders
Irritability
|
7.8%
57/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
21.1%
155/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Nervous system disorders
Dizziness
|
6.0%
44/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
|
Psychiatric disorders
Anxiety
|
5.9%
43/733 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/155 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/80 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
0.00%
0/339 • From first dose through 30 days after last dose of study drug (Up to approximately Week 15)
Safety Sample consisted of randomized participants who received at least one dose of double-blind IMP as indicated on the dosing record. As pre-specified in the protocol the data for adverse events is presented in Part A, Part B and Part A+ as per the dose received.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
- Publication restrictions are in place
Restriction type: OTHER