Trial Outcomes & Findings for Study of Flexible Doses of the Triple Reuptake Inhibitor EB-1020 Sustained Release (SR) in the Treatment of Adult Males With Attention-Deficit Hyperactivity Disorder (NCT NCT01939353)
NCT ID: NCT01939353
Last Updated: 2021-10-18
Results Overview
The ADHD-RS-IV consists of 18 items with first 9 items assessing inattentive symptoms and the last 9 items assessing hyperactive-impulsive symptoms scored on a 4-point Likert-type severity scale with 0 (none), 1 (mild), 2 (moderate), and 3 (severe) with a total score ranging from 0 to 54. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. A negative change from Baseline indicates improvement.
COMPLETED
PHASE2
45 participants
Baseline, Week 4
2021-10-18
Participant Flow
Participants took part in the study at 3 investigative sites in the United States from 03 October 2013 to 20 February 2014.
A total of 45 male participants diagnosed with attention-deficit hyperactivity disorder (ADHD) were enrolled at Baseline-1 in a 1-week single-blind (SB) placebo run-in treatment to receive placebo from Baseline-1 to Baseline-2. At Baseline-2, remaining 41 out of 45 participants who had \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received centanafadine (CTN) sustained release (SR) 100-500 mg, tablets from Week 1 to Week 4.
Participant milestones
| Measure |
Centanafadine SR 100-500 mg
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Placebo Run-in (1 Week)
STARTED
|
45
|
|
Placebo Run-in (1 Week)
COMPLETED
|
41
|
|
Placebo Run-in (1 Week)
NOT COMPLETED
|
4
|
|
CTN SR Treatment Phase (4 Weeks)
STARTED
|
41
|
|
CTN SR Treatment Phase (4 Weeks)
COMPLETED
|
37
|
|
CTN SR Treatment Phase (4 Weeks)
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Centanafadine SR 100-500 mg
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Placebo Run-in (1 Week)
Withdrew Consent
|
3
|
|
Placebo Run-in (1 Week)
Lost to Follow-up
|
1
|
|
CTN SR Treatment Phase (4 Weeks)
Treatment Emergent Adverse Event (TEAE)/Serious Adverse Event (SAE)
|
2
|
|
CTN SR Treatment Phase (4 Weeks)
Lost to Follow-up
|
1
|
|
CTN SR Treatment Phase (4 Weeks)
Withdrew Consent
|
1
|
Baseline Characteristics
Study of Flexible Doses of the Triple Reuptake Inhibitor EB-1020 Sustained Release (SR) in the Treatment of Adult Males With Attention-Deficit Hyperactivity Disorder
Baseline characteristics by cohort
| Measure |
Centanafadine SR 100-500 mg
n=41 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
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|---|---|
|
Age, Continuous
|
37.71 years
STANDARD_DEVIATION 11.87 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
37 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
03 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
01 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Hispanic or Latino
|
04 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Not Hispanic or Latino
|
37 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 4Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations.
The ADHD-RS-IV consists of 18 items with first 9 items assessing inattentive symptoms and the last 9 items assessing hyperactive-impulsive symptoms scored on a 4-point Likert-type severity scale with 0 (none), 1 (mild), 2 (moderate), and 3 (severe) with a total score ranging from 0 to 54. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Change From Baseline-2 in ADHD Symptoms to Week 4 as Assessed by the Adult Attention-Deficit Hyperactivity Disorder Rating Scale (AD HD-RS-IV)
Baseline-2
|
38.70 score on a scale
Standard Deviation 6.19
|
|
Change From Baseline-2 in ADHD Symptoms to Week 4 as Assessed by the Adult Attention-Deficit Hyperactivity Disorder Rating Scale (AD HD-RS-IV)
Change from Baseline-2 at Week 4
|
-21.41 score on a scale
Standard Deviation 10.74
|
SECONDARY outcome
Timeframe: Baseline-2, Weeks 1, 2, 3, and 6 (Follow-up Visit)Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
The ADHD-RS-IV consists of 18 items with first 9 items assessing inattentive symptoms and the last 9 items assessing hyperactive-impulsive symptoms scored on a 4-point Likert-type severity scale with 0 (none), 1 (mild), 2 (moderate), and 3 (severe) with a total score ranging from 0 to 54. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
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|---|---|
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Change From Baseline-2 in ADHD Symptoms as Assessed by the Adult ADHD-RS-IV
Baseline-2
|
38.70 score on a scale
Standard Deviation 6.19
|
|
Change From Baseline-2 in ADHD Symptoms as Assessed by the Adult ADHD-RS-IV
Change from Baseline-2 at Treatment Week 1
|
-11.14 score on a scale
Standard Deviation 8.64
|
|
Change From Baseline-2 in ADHD Symptoms as Assessed by the Adult ADHD-RS-IV
Change from Baseline-2 at Treatment Week 2
|
-16.14 score on a scale
Standard Deviation 11.08
|
|
Change From Baseline-2 in ADHD Symptoms as Assessed by the Adult ADHD-RS-IV
Change from Baseline-2 at Treatment Week 3
|
-20.86 score on a scale
Standard Deviation 11.11
|
|
Change From Baseline-2 in ADHD Symptoms as Assessed by the Adult ADHD-RS-IV
Change from Baseline-2 at Week 6 (Follow-up Visit)
|
-11.53 score on a scale
Standard Deviation 8.78
|
SECONDARY outcome
Timeframe: Baseline-2 and Week 4Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations.
BRIEF-A is a standardized self-administered scale that captures an adult's executive functions or self-regulation in their everyday environment, composed of 75 items within 9 nonoverlapping derived clinical scales and measures various aspects of executive functioning, including the following: inhibit, self-monitor shift, emotional control, initiate, working memory, plan/organize, monitor, and organization of materials. Items are rated 1=never, 2=sometimes, and 3=often; total raw scale score ranges from 75-225, higher total scores=more problems with executive functioning. Raw scale scores are used to generate T-scores. Total T-scores range from 30 to 90, with broader composite indexes including Behavioral Regulation Index(BRI) and Metacognition Index(Ml). These indexes form overall summary score, the Global Executive Composite(GEC). Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
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|---|---|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
RAW Score: BRI at Baseline-2
|
57.11 score on a scale
Standard Deviation 10.96
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
RAW Score: Change from Baseline-2 in BRI at Week 4
|
-8.38 score on a scale
Standard Deviation 9.42
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
RAW Score: MI at Baseline-2
|
88.08 score on a scale
Standard Deviation 13.46
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
RAW Score: Change from Baseline-2 in MI at Week 4
|
-13.70 score on a scale
Standard Deviation 15.69
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
RAW Score: GEC at Baseline-2
|
145.19 score on a scale
Standard Deviation 22.27
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
RAW Score: Change from Baseline-2 in GEC at Week 4
|
-22.08 score on a scale
Standard Deviation 24.54
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
T-Score: BRI at Baseline-2
|
65.62 score on a scale
Standard Deviation 11.99
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
T-Score: Change from Baseline-2 in BRI at Week 4
|
-8.93 score on a scale
Standard Deviation 10.07
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
T-Score: MI at Baseline-2
|
74.26 score on a scale
Standard Deviation 10.71
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
T-Score: Change from Baseline-2 in MI at Week 4
|
-10.83 score on a scale
Standard Deviation 12.37
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
T-Score: GEC at Baseline-2
|
71.86 score on a scale
Standard Deviation 11.43
|
|
Change From Baseline-2 to Week 4 on the Behavior Rating Inventory of Executive Function, Adult Version (BRIEF-A) Scale
T-Score: Change from Baseline-2 in GEC at Week 4
|
-10.86 score on a scale
Standard Deviation 12.04
|
SECONDARY outcome
Timeframe: Baseline-2, Weeks 1, 2, 3, and 4Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations.
Responders are defined as participants with ≥30% improvement in ADHD symptoms compared with Baseline-2, as measured by the ADHD-RS-IV. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
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|---|---|
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Percentage of Participants Who Are Responders for ADHD Symptoms as Measured by the ADHD-RS-IV
Week 1
|
35.14 percentage of participants
|
|
Percentage of Participants Who Are Responders for ADHD Symptoms as Measured by the ADHD-RS-IV
Week 2
|
62.16 percentage of participants
|
|
Percentage of Participants Who Are Responders for ADHD Symptoms as Measured by the ADHD-RS-IV
Week 3
|
75.68 percentage of participants
|
|
Percentage of Participants Who Are Responders for ADHD Symptoms as Measured by the ADHD-RS-IV
Week 4
|
81.08 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline-2, Weeks 1, 2, 3, and 4Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations.
High responders are defined as participants with ≥50% improvement in ADHD symptoms compared with Baseline-2, as measured by the ADHD-RS-IV. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
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|---|---|
|
Percentage of Participants Who Are High Responders for ADHD Symptoms as Measured by the ADHD-RS-IV
Week 1
|
16.22 percentage of participants
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|
Percentage of Participants Who Are High Responders for ADHD Symptoms as Measured by the ADHD-RS-IV
Week 2
|
43.24 percentage of participants
|
|
Percentage of Participants Who Are High Responders for ADHD Symptoms as Measured by the ADHD-RS-IV
Week 3
|
62.16 percentage of participants
|
|
Percentage of Participants Who Are High Responders for ADHD Symptoms as Measured by the ADHD-RS-IV
Week 4
|
62.16 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline-2, Weeks 1, 2, 3 and 4Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations.
The ADHD-RS-IV consists of 18 items with first 9 items assessing inattentive symptoms and the last 9 items assessing hyperactive-impulsive symptoms scored on a 4-point Likert-type severity scale with 0=none, 1=mild, 2=moderate, and 3=severe, with a total score ranging from 0 to 54. Inattention and hyperactivity/impulsivity subscales consist of 9 items each, for total subscale scores ranging from 0 to 27. Higher scores are indicative of more severe symptoms. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Inattention Symptoms at Baseline-2
|
22.81 score on a scale
Standard Deviation 2.55
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Change from Baseline-2 in Inattention Symptoms at Week 1
|
-6.32 score on a scale
Standard Deviation 4.99
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Change from Baseline-2 in Inattention Symptoms at Week 2
|
-9.76 score on a scale
Standard Deviation 6.40
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Change from Baseline-2 in Inattention Symptoms at Week 3
|
-12.16 score on a scale
Standard Deviation 6.61
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Change from Baseline-2 in Inattention Symptoms at Week 4
|
-12.41 score on a scale
Standard Deviation 6.66
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Hyperactive/Impulsive Symptoms at Baseline-2
|
15.89 score on a scale
Standard Deviation 4.80
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Change from Baseline-2 in Hyperactive/Impulsive Symptoms at Week 1
|
-4.81 score on a scale
Standard Deviation 4.74
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Change from Baseline-2 in Hyperactive/Impulsive Symptoms at Week 2
|
-6.38 score on a scale
Standard Deviation 5.94
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Change from Baseline-2 in Hyperactive/Impulsive Symptoms at Week 3
|
-8.70 score on a scale
Standard Deviation 5.81
|
|
Change From Baseline-2 on the Inattentiveness and Hyperactivity/Impulsivity Subscales of ADHD-RS-IV
Change from Baseline-2 in Hyperactive/Impulsive Symptoms at Week 4
|
-9.00 score on a scale
Standard Deviation 5.24
|
SECONDARY outcome
Timeframe: Baseline-2, Weeks 1, 2, 3, 4 and 6 (Follow-up Visit)Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations. Number analyzed is the number of participants with data available for analysis at the given timepoint.
CGI-S is an observer-rated scale that is used to assess the severity of the participants condition on a 7-point scale ranging from 1 to 7, where 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. This rating is based upon observed and reported symptoms, behavior, and function in the past 7 days with a minimum score of 1 and maximum score of 7. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Change From Baseline-2 in the Clinical Global Impression of Severity (CGI-S) [ADHD Version] Scale Score
Change from Baseline-2 in CGI-S Score at Week 6 (Follow-up)
|
-0.92 score on a scale
Standard Deviation 0.91
|
|
Change From Baseline-2 in the Clinical Global Impression of Severity (CGI-S) [ADHD Version] Scale Score
Baseline-2
|
4.68 score on a scale
Standard Deviation 0.47
|
|
Change From Baseline-2 in the Clinical Global Impression of Severity (CGI-S) [ADHD Version] Scale Score
Change from Baseline-2 in CGI-S Score at Week 1
|
-0.81 score on a scale
Standard Deviation 0.70
|
|
Change From Baseline-2 in the Clinical Global Impression of Severity (CGI-S) [ADHD Version] Scale Score
Change from Baseline-2 in CGI-S Score at Week 2
|
-1.30 score on a scale
Standard Deviation 0.91
|
|
Change From Baseline-2 in the Clinical Global Impression of Severity (CGI-S) [ADHD Version] Scale Score
Change from Baseline-2 in CGI-S Score at Week 3
|
-1.73 score on a scale
Standard Deviation 0.96
|
|
Change From Baseline-2 in the Clinical Global Impression of Severity (CGI-S) [ADHD Version] Scale Score
Change from Baseline-2 in CGI-S Score at Week 4
|
-1.89 score on a scale
Standard Deviation 1.13
|
SECONDARY outcome
Timeframe: Baseline-2, Weeks 1, 2, 3, 4 and 6 (Follow-up)Population: Data for this outcome measure was not collected as Baseline-2 CGI-I values were not recorded.
CGl-I is an observer-rated scale to assess how much the participant's illness has improved or worsened relative to a Baseline state, with scores ranging from 1 to 7. It consists of a 7-point scale ranging from 1 to 7, where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from Baseline-2 (the initiation of treatment); 5=minimally worse; 6=much worse; and 7=very much worse since the initiation of treatment. Improvement is defined as a score of 1=very much improved or 2=much improved on the scale. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 4 and 6 (Follow-up Visit)Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.
CGl-I is an observer-rated scale to assess how much the participant's illness has improved or worsened relative to a Baseline state, with scores ranging from 1 to 7. It consists of a 7-point scale ranging from 1 to 7, where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from Baseline-2 (the initiation of treatment); 5=minimally worse; 6=much worse; and 7=very much worse since the initiation of treatment. Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. Responders are defined as those who had CGI-I (ADHD version) scores of much or very much improved.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline-2, Weeks 1, 4, and 6 (Follow-up Visit)Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.
C-SSRS is a brief method of assessing both behavior and ideation that tracks all suicidal events, and provides a summary of suicidality. It assesses the lethality of attempts and other features of ideation (frequency, duration, controllability, reasons for ideation, and deterrents), all of which are significantly predictive of completed suicide. Severity of suicidal ideation is rated on a 6-point scale from 0=no ideation present to 5=active ideation with plan and intent. Suicidal behavior was collected as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline-2 and Week 4Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. Change from Baseline-2 for the POMS 2-A Short version scale is calculated using summary T-scores.
POMS 2-A Short version consists of a subset of 35 items from the full-length version of 72 mood adjectives assessing 7 mood domains namely, anger-hostility, confusion-bewilderment, depression-dejection, fatigue-inertia, tension-anxiety, vigor-activity, and friendliness. High scores indicate better vigor-activity and friendliness, but more severe symptoms for the five other domains. In addition, the Total Mood Disturbance (TMD) score is calculated from anger-hostility, confusion-bewilderment, depression-dejection, fatigue-inertia, tension-anxiety, and vigor-activity. Participants rated each of the 35 items using 4-point Likert-type scale (0=much unlike this; 3=much like this). Items from each domain are summed T-score such that total scores were in the negative-mood direction (i.e., higher scores indicate greater experience of negative moods). Total scores range from 0 to 100. TMD is calculated based on a standard value (mean of 50 and standard deviation of 10).
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
TMD at Baseline-2
|
49.81 score on a scale
Standard Deviation 8.34
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Change from Baseline-2 in TMD at Week 4
|
-2.81 score on a scale
Standard Deviation 8.08
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Tension-Anxiety at Baseline-2
|
48.65 score on a scale
Standard Deviation 9.41
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Change from Baseline-2 in Tension-Anxiety at Week 4
|
-3.92 score on a scale
Standard Deviation 8.38
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Depression-Dejection at Baseline-2
|
45.41 score on a scale
Standard Deviation 5.09
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Change from Baseline-2 in Depression-Dejection at Week 4
|
0.05 score on a scale
Standard Deviation 5.82
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Anger-Hostility at Baseline-2
|
46.70 score on a scale
Standard Deviation 7.07
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Change from Baseline-2 in Anger-Hostility at Week 4
|
-1.78 score on a scale
Standard Deviation 5.52
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Fatigue-Inertia at Baseline-2
|
44.62 score on a scale
Standard Deviation 9.41
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Change from Baseline-2 in Fatigue-Inertia at Week 4
|
-1.73 score on a scale
Standard Deviation 8.28
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Confusion- Bewilderment at Baseline-2
|
54.54 score on a scale
Standard Deviation 10.52
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Change from Baseline-2 in Confusion-Bewilderment at Week 4
|
-6.76 score on a scale
Standard Deviation 10.20
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Vigor-Activity at Baseline-2
|
53.95 score on a scale
Standard Deviation 8.04
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Change from Baseline-2 in Vigor-Activity at Week 4
|
-3.16 score on a scale
Standard Deviation 7.87
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Friendliness at Baseline-2
|
50.59 score on a scale
Standard Deviation 7.47
|
|
Change From Baseline-2 on the Profile of Mood States, Second Edition, Short Version 2A (POMS 2-A Short) at Week 4
Change from Baseline-2 in Friendliness at Week 4
|
-0.19 score on a scale
Standard Deviation 7.05
|
SECONDARY outcome
Timeframe: Baseline-2 and Week 4Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations.
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, hyperactivity, affective lability, hot temper, stress intolerance, disorganization, and impulsivity. 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 to 56), higher scores indicate worsening of symptoms. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with CTN SR. A negative change from Baseline indicates improvement. Change from Baseline-2 for the WRAADDS scale is calculated using total scores.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Change From Baseline-2 on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) at Week 4
WRAADDS Total Score at Baseline-2
|
33.59 score on a scale
Standard Deviation 7.86
|
|
Change From Baseline-2 on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) at Week 4
Change from Baseline-2 in WRAADDS Total Score at Week 4
|
-15.59 score on a scale
Standard Deviation 12.25
|
SECONDARY outcome
Timeframe: Baseline and Week 4Population: Per-protocol Population included all participants who met inclusion/exclusion criteria and completed the trial (4 weeks of drug treatment with evaluable data after Week 4) without major protocol violations. Baseline-2 is defined as an end of 1-week SB placebo run-in and beginning of treatment with EB-1020 SR. A negative change from Baseline indicates improvement. Change from Baseline-2 for the WFIRS-S scale is calculated using average total scores.
The WFIRS-S is a validated rating scale used to capture functional difficulties in the lives of individuals with ADHD. It investigates emotional or behavioral problems and is comprised of 69 items grouped into six domains: family (8 items), work (11 items), school (10 items, includes learning \[4 items\] and behavior \[6 items\]), life skills (12 items), self-concept (5 items), social (9 items), and risky (14 items). It uses a 4-point Likert scale where 0=never or not at all, 1=sometimes or somewhat, 2=often or much, and 3=very often or very much. Any item rating of 2 or 3 was considered in the clinically impaired range. A total score was derived by summing all scores from every domain, ranging from 0 to 207 with higher scores=greater ADHD-related functional impairment.
Outcome measures
| Measure |
Centanafadine SR 100-500 mg
n=37 Participants
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Change From Baseline-2 on the Weiss Functional Impairment Rating Scale - Self Report (WFIRS-S) at Week 4
WFIRS-S Total Score at Baseline-2
|
0.723 score on a scale
Standard Deviation 0.304
|
|
Change From Baseline-2 on the Weiss Functional Impairment Rating Scale - Self Report (WFIRS-S) at Week 4
Change from Baseline-2 in WFIRS-S Total Score at Week 4
|
-0.258 score on a scale
Standard Deviation 0.276
|
SECONDARY outcome
Timeframe: Week 4 and end of Discontinuation Phase (Week 6)Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.
The change on the ADHD-RS-IV was used to assess relapse of symptoms after end of investigational product administration.
Outcome measures
Outcome data not reported
Adverse Events
Centanafadine SR 100-500 mg
Serious adverse events
| Measure |
Centanafadine SR 100-500 mg
n=41 participants at risk
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Vascular disorders
Cerebrovascular accident
|
2.4%
1/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
Other adverse events
| Measure |
Centanafadine SR 100-500 mg
n=41 participants at risk
Following a 1-week SB placebo run-in treatment, participants with \<30% improvement and ≥28 total score on Adult ADHD-RS-IV scale score received CTN 100 mg, SR tablet, once daily (1 tablet in the morning) on Days 1 and 2, followed by 200 mg, SR tablets, twice daily (1 tablet in the morning and 1 tablet 5 hours later) on Days 3 and 4, followed by 300 mg, SR tablets, twice daily (2 tablets in the morning and 1 tablet 5 hours later) on Days 5, 6, and 7. After 1 week of treatment, CTN doses were maintained or titrated in 100-mg increments up to the maximum of 500 mg daily or reduced based on the safety and tolerability, as judged by the investigator at Weeks 2, 3 and 4.
|
|---|---|
|
Cardiac disorders
Tachycardia
|
4.9%
2/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Gastrointestinal disorders
Diarrhea
|
29.3%
12/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Gastrointestinal disorders
Dry mouth
|
14.6%
6/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Gastrointestinal disorders
Dyspepsia
|
9.8%
4/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Gastrointestinal disorders
Vomiting
|
7.3%
3/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Gastrointestinal disorders
Nausea
|
4.9%
2/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.3%
3/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
14.6%
6/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Nervous system disorders
Headache
|
17.1%
7/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Insomnia
|
9.8%
4/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Irritability
|
9.8%
4/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Abnormal dreams
|
7.3%
3/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Anxiety
|
7.3%
3/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Middle insomnia
|
7.3%
3/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Lethargy
|
7.3%
3/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Dysphoria
|
7.3%
3/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Erectile dysfunction
|
4.9%
2/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
|
Psychiatric disorders
Somnolence
|
4.9%
2/41 • Baseline-2 through end of the study (Up to Week 6)
Safety Population included all participants who received at least 1 dose of CTN SR (not placebo) as indicated in the treatment regimen.
|
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