A Trial Evaluating the Efficacy, Safety, & Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03605680
• Collaborator: (none)
• Enrollment: 604
• Location: 1
• Arms: 4
• Actual Duration (Months): 14.8
• Patients Per Site Per Month: 40.8

Study Details

Study Description

Brief Summary

This study evaluates the efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults with attention-deficit/hyperactivity disorder (ADHD). Participants will either receive a twice-daily dose of centanafadine sustained-release tablets, or twice-daily placebo.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Disorder; Attention Deficit Hyperactivity Disorder	Drug: Centanafadine SR; Other: Placebo; Drug: Centanafadine SR	Phase 3

Detailed Description

Screening & Washout Period: up to 28 days Investigational Treatment Period: 49 days Follow-up Period : 7 days or 10 days

Study Design

• Study Type: Interventional
• Actual Enrollment: 604 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel-group Trial Evaluating the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder
• Actual Study Start Date: Jan 16, 2019
• Actual Primary Completion Date: Apr 11, 2020
• Actual Study Completion Date: Apr 11, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-blind Run-in Period: Placebo Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1).	Other: Placebo; BID, oral tablet.
Experimental: Double-blind Treatment Period: Centanafadine SR 200 mg Following Single-blind Run-in Period, participants with <30% improvement on Adult ADHD Self Report Scale (ASRS) scale score were randomized to receive centanafadine 200 mg SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Drug: Centanafadine SR; 100 mg, BID, oral tablets; Other Names: EB-1020
Experimental: Double-blind Treatment Period: Centanafadine SR 400 mg Following Single-blind Run-in Period, participants with <30% improvement on Adult ADHD Self Report Scale (ASRS) scale score were randomized to receive centanafadine 400 mg SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Drug: Centanafadine SR; 200 mg, BID, oral tablets; Other Names: EB-1020
Placebo Comparator: Double-blind Treatment Period: Placebo Following Single-blind Run-in Period, participants with <30% improvement on Adult ADHD Self Report Scale (ASRS) scale score were randomized to receive centanafadine SR matching placebo tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Other: Placebo; BID, oral tablet.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS) [Baseline and Day 42]

   The Adult Investigator Symptom Rating Scale (AISRS) is an 18-item clinician rating scale to evaluate individual ADHD symptoms on a scale of 0 (none) to 3 (severe). The total sum ranges from 0 (no ADHD symptoms) to 54 (extremely severe ADHD symptoms). Negative change from Baseline indicates improvement. Mixed-effect model repeated measure (MMRM) was used for analysis.

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) [Baseline and Day 42]

   CGI-S is an observer-rated scale used to measure symptom severity with a total score range of 0 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 participants. A negative change from Baseline indicates improvement. MMRM was used for the analysis.

Other Outcome Measures

1. Adverse Event Reporting [Up to 59 days]

   Frequency and severity of treatment-emergent adverse events (TEAEs) will be assessed to determine safety and tolerability of centanafadine SR tablets.

2. ADHD Impact Module - Adult (AIM-A) [Up to 42 days]

   Scale composed of 3 subscales with a maximum score of 100. A lower score indicates a worse outcome. Exploratory endpoint; comparison of baseline score to other points throughout the study.

3. Adult ADHD Self Report Scale (ASRS) [Up to 42 days]

   An 18 question report, total score ranges from 0 to 124. A higher score denotes a worse outcome. Exploratory endpoint; comparison of baseline score to other points throughout the study.

4. Adult ADHD Investigator Symptom Rating Scale (AISRS) [Up to 42 days]

   Change from baseline total score compared to every scheduled visit. Each subscale is composed of 9 items each. Scores can range from 0 to 27, with a higher score representing a worse outcome. Change from baseline scores are compared to every scheduled visit score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must meet the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for ADHD (including predominantly inattentive presentation, hyperactive presentation, or combined presentation) as confirmed by the Adult ADHD Clinical Diagnostic Scale (ACDS) Version 1.2. To confirm that ADHD is the primary diagnosis, the Mini International Neuropsychiatric Interview (MINI) will be used to identify and exclude other psychiatric conditions which would preclude enrollment.

• Participants who were not receiving any pharmacological treatment for ADHD must have an Adult ADHD Investigator Symptom Rating Scale (AISRS) score of ≥ 28 at screening and baseline. Participants who were receiving pharmacological treatment for ADHD at screening must have a minimum AISRS score of ≥ 22 at screening, and a score of ≥ 28 at baseline.

• All participants must be willing to discontinue all prohibited psychotropic medications starting from the time of signing the informed consent through the 7-day follow-up period. Participants that do not rollover into Trial 405-201-00015 (NCT03605849) must be willing to discontinue all prohibited psychotropic medications starting from the time of signing the informed consent until after the follow-up telephone call 10 days after the last dose of investigational medicinal product (IMP).

• Participants must have a Clinical Global Impression-Severity of Illness Scale (CGI-S) score of ≥ 4 (≥ moderate impairment) at baseline.

Exclusion Criteria:

• Participants with a DSM-5 diagnosis of Other Specified or Unspecified Attention Deficit/Hyperactivity Disorder.

• Participants has a current comorbid psychiatric disorder that either could be expected to require treatment with medications prohibited in this trial, or to confound efficacy or safety assessments. Examples include, but are not limited to, psychotic disorder, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, a current major depressive episode, or posttraumatic stress disorder, as established by the Mini International Neuropsychiatric Interview (MINI).

• In the opinion of the investigator, participants has not derived significant therapeutic benefit from 2 or more ADHD therapies of 2 different classes (eg, amphetamine and methylphenidate) given with an acceptable dose and duration during adulthood (aged 18 or older). NOTE: If participants has not derived significant therapeutic benefit due to an inability to tolerate side effects, eligibility can be discussed on case-by-case basis with the medical monitor.

• Participants who have a positive alcohol test (via breathalyzer or blood), a positive drug screen assessed prior to the baseline visit for cocaine, other illicit drugs (including marijuana), or prescription or over-the-counter (OTC) ADHD medications will be early terminated. This includes medications such as opioids or benzodiazepines taken without prescription.

• In the opinion of the investigator, the participants is unable to adhere to the treatment regimen or other requirements outlined in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding sites, contact 844-687-8522	New York	New York	United States	10022

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 15, 2020
• Statistical Analysis Plan - Apr 27, 2020

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT03605680
• Other Study ID Numbers: 405-201-00013
• First Posted: Jul 30, 2018
• Last Update Posted: Mar 15, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Centanafadine; ADHD; ADD
• Additional relevant MeSH terms: Hyperkinesis; Disease; Attention Deficit Disorder with Hyperactivity

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 45 investigative sites in the United States from 16 January 2019 to 11 April 2020.
Pre-assignment Detail	A total of 604 participants were enrolled in the study, out of which 584 were treated during the placebo Run-in Period. Out of 584, 466 participants were randomized into one of the three treatment groups (centanafadine 200 mg, centanafadine 400 mg, or placebo) in the Double-blind Treatment Period.

Arm/Group Title	Single-blind (SB) Run-in Period: Placebo	Double-blind Treatment Period: Centanafadine SR 200 mg	Double-blind Treatment Period: Centanafadine SR 400 mg	Double-blind Treatment Period: Placebo
Arm/Group Description	Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1).	Following Single-blind Run-in Period, participants with <30% improvement on Adult ASRS scale score were randomized to receive centanafadine 200 mg SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Following Single-blind Run-in Period, participants with <30% improvement on Adult ASRS scale score were randomized to receive centanafadine SR 200 mg tablets BID orally on Day 1 through Day 7 and were then escalated to their target total daily dose (TDD) of centanafadine 400 mg on Day 8 through Day 42 in the Double-blind Treatment Period.	Following Single-blind Run-in Period, participants with <30% improvement on ASRS scale score were randomized to receive centanafadine matching placebo SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.
Period Title: SB Placebo Run-in Period (1 Week)
STARTED	604	0	0	0
Treated	584	0	0	0
COMPLETED	466	0	0	0
NOT COMPLETED	138	0	0	0
Period Title: SB Placebo Run-in Period (1 Week)
STARTED	0	154	156	156
COMPLETED	0	110	117	121
NOT COMPLETED	0	44	39	35

Baseline Characteristics

Arm/Group Title	Placebo: Single-blind Run-in Period Only	Double-blind Treatment Period: Placebo + Centanafadine SR 200 mg	Double-blind Treatment Period: Placebo + Centanafadine SR 400 mg	Double-blind Treatment Period: Placebo + Placebo	Total
Arm/Group Description	Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1) in the Run-in Period only. Participants did not continue to Double-blind Treatment Period.	Participants received centanafadine SR matching placebo tablets in Single-blind Run-in Period. Participants who showed >=30% improvement in Adult ASRS at Baseline were early terminated and the remaining participants were randomized to receive centanafadine SR 200 mg tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Participants received centanafadine SR matching placebo tablets in Single-blind Run-in Period. Participants who showed >=30% improvement in Adult ASRS at Baseline were early terminated and the remaining participants were randomized to receive centanafadine SR 200 mg tablets BID orally on Day 1 through Day 7 and were then escalated to their target TDD of centanafadine 400 mg on Day 8 through Day 42 in the Double-blind Treatment Period.	Participants received centanafadine SR matching placebo tablets in Single-blind Run-in Period. Participants who showed >=30% improvement in Adult ASRS at Baseline were early terminated and the remaining participants were randomized to receive centanafadine SR matching placebo tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Total of all reporting groups
Overall Participants	138	154	156	156	604
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.1 (9.4)	36.6 (9.8)	35.3 (10.4)	35.0 (9.9)	35.0 (9.9)
Sex: Female, Male (Count of Participants)
Female	57 41.3%	76 49.4%	75 48.1%	76 48.7%	284 47%
Male	81 58.7%	78 50.6%	81 51.9%	80 51.3%	320 53%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	28 20.3%	34 22.1%	38 24.4%	29 18.6%	129 21.4%
Not Hispanic or Latino	110 79.7%	119 77.3%	116 74.4%	124 79.5%	469 77.6%
Unknown or Not Reported	0 0%	1 0.6%	2 1.3%	3 1.9%	6 1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	0 0%	3 1.9%	0 0%	4 0.7%
Asian	5 3.6%	4 2.6%	2 1.3%	4 2.6%	15 2.5%
Native Hawaiian or Other Pacific Islander	1 0.7%	1 0.6%	1 0.6%	0 0%	3 0.5%
Black or African American	22 15.9%	19 12.3%	23 14.7%	21 13.5%	85 14.1%
White	107 77.5%	126 81.8%	123 78.8%	130 83.3%	486 80.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.4%	4 2.6%	4 2.6%	1 0.6%	11 1.8%
Adult Attention-deficit/Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	39.7 (6.7)	39.4 (6.8)	39.4 (7.1)	39.5 (6.8)
Clinical Global Impression-Severity of Illness Scale (CGI-S) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	4.5 (0.6)	4.5 (0.6)	4.5 (0.6)	4.5 (0.6)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS)
Description	The Adult Investigator Symptom Rating Scale (AISRS) is an 18-item clinician rating scale to evaluate individual ADHD symptoms on a scale of 0 (none) to 3 (severe). The total sum ranges from 0 (no ADHD symptoms) to 54 (extremely severe ADHD symptoms). Negative change from Baseline indicates improvement. Mixed-effect model repeated measure (MMRM) was used for analysis.
Time Frame	Baseline and Day 42

Outcome Measure Data

Analysis Population Description

Efficacy sample FAS included all participants in the safety sample who had a Baseline value and at least one valid post-randomization efficacy evaluation for AISRS total score in the Double-blind Treatment Period. Overall number analysed are the participants with data available for analysis.

Arm/Group Title	Double-blind Treatment Period: Centanafadine SR 200 mg	Double-blind Treatment Period: Centanafadine SR 400 mg	Double-blind Treatment Period: Placebo
Arm/Group Description	Following Single-blind Run-in Period, participants with <30% improvement on Adult ASRS scale score were randomized to receive centanafadine 200 mg SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Following Single-blind Run-in Period, participants with <30% improvement on Adult ASRS scale score were randomized to receive centanafadine SR 200 mg tablets BID orally on Day 1 through Day 7 and were then escalated to their target TDD of centanafadine 400 mg on Day 8 through Day 42 in the Double-blind Treatment Period.	Following Single-blind Run-in Period, participants with <30% improvement on Adult ASRS scale score were randomized to receive centanafadine matching placebo SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.
Measure Participants	147	147	144
Least Squares Mean (Standard Error) [score on a scale]	-10.1 (0.99)	-9.73 (0.98)	-6.98 (0.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind Treatment Period: Centanafadine SR 200 mg, Double-blind Treatment Period: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.0193
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS ) Mean Difference
	Estimated Value	-3.15
	Confidence Interval	(2-Sided) 95%; -5.79 to -0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		The comparison between the centanafadine and the placebo group was tested at a significance level of 0.05.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-blind Treatment Period: Centanafadine SR 400 mg, Double-blind Treatment Period: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.0392
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.74
	Confidence Interval	(2-Sided) 95%; -5.35 to -0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S)
Description	CGI-S is an observer-rated scale used to measure symptom severity with a total score range of 0 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 participants. A negative change from Baseline indicates improvement. MMRM was used for the analysis.
Time Frame	Baseline and Day 42

Outcome Measure Data

Analysis Population Description

Efficacy sample FAS included all participants in the safety sample who had a Baseline value and at least one valid post-randomization efficacy evaluation for AISRS total score in the Double-blind Treatment Period. Overall number analysed are the participants with data available for analysis.

Arm/Group Title	Double-blind Treatment Period: Centanafadine SR 200 mg	Double-blind Treatment Period: Centanafadine SR 400 mg	Double-blind Treatment Period: Placebo
Arm/Group Description	Following Single-blind Run-in Period, participants with <30% improvement on Adult ASRS scale score were randomized to receive centanafadine 200 mg SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.	Following Single-blind Run-in Period, participants with <30% improvement on Adult ASRS scale score were randomized to receive centanafadine SR 200 mg tablets BID orally on Day 1 through Day 7 and were then escalated to their target TDD of centanafadine 400 mg on Day 8 through Day 42 in the Double-blind Treatment Period.	Following Single-blind Run-in Period, participants with <30% improvement on Adult ASRS scale score were randomized to receive centanafadine matching placebo SR tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.
Measure Participants	146	147	144
Least Squares Mean (Standard Error) [score on a scale]	-0.78 (0.09)	-0.79 (0.08)	-0.52 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind Treatment Period: Centanafadine SR 200 mg, Double-blind Treatment Period: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.0232
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.50 to -0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		The comparison between the centanafadine and the placebo group was tested at a significance level of 0.05.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-blind Treatment Period: Centanafadine SR 400 mg, Double-blind Treatment Period: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.0162
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.51 to -0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		The comparison between the centanafadine and the placebo group was tested at a significance level of 0.05.

3. Other Pre-specified Outcome

Title	Adverse Event Reporting
Description	Frequency and severity of treatment-emergent adverse events (TEAEs) will be assessed to determine safety and tolerability of centanafadine SR tablets.
Time Frame	Up to 59 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	ADHD Impact Module - Adult (AIM-A)
Description	Scale composed of 3 subscales with a maximum score of 100. A lower score indicates a worse outcome. Exploratory endpoint; comparison of baseline score to other points throughout the study.
Time Frame	Up to 42 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Adult ADHD Self Report Scale (ASRS)
Description	An 18 question report, total score ranges from 0 to 124. A higher score denotes a worse outcome. Exploratory endpoint; comparison of baseline score to other points throughout the study.
Time Frame	Up to 42 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Adult ADHD Investigator Symptom Rating Scale (AISRS)
Description	Change from baseline total score compared to every scheduled visit. Each subscale is composed of 9 items each. Scores can range from 0 to 27, with a higher score representing a worse outcome. Change from baseline scores are compared to every scheduled visit score.
Time Frame	Up to 42 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 59 days
Adverse Event Reporting Description	Safety sample included randomized participants who received at least 1 dose of study drug. The Placebo: Single-blind Run-in Period Only arm includes AEs that occurred during single-blind run-in period for participants who received at least 1 dose of study drug but did not participate in DB period. As pre-specified in SAP, AEs that occurred in Single-blind Placebo Run-In period for participants who received treatment in DB period was reported in DB treatment arms based on DB treatment received.
Arm/Group Title	Placebo: SB Run-in Period Only		Placebo + Centanafadine SR 200 mg		Placebo + Centanafadine SR 400 mg		Placebo + Placebo
Arm/Group Description	Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1) in the Single-blind Run-in Period only. Participants did not continue to Double-blind Treatment Period.		Participants received centanafadine SR matching placebo tablets in Single-blind Run-in Period. Participants who showed >=30% improvement in ASRS at Baseline were early terminated and the remaining participants were randomized to receive centanafadine SR 200 mg tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.		Participants received centanafadine SR matching placebo tablets in Single-blind Run-in Period. Participants who showed >=30% improvement in ASRS at Baseline were early terminated and the remaining participants were randomized to receive centanafadine SR 200 mg tablets BID orally on Day 1 through Day 7 and were then escalated to their target TDD of centanafadine 400 mg on Day 8 through Day 42 in the Double-blind Treatment Period.		Participants received centanafadine SR matching placebo tablets in Single-blind Run-in Period. Participants who showed >=30% improvement in ASRS at Baseline were early terminated and the remaining participants were randomized to receive centanafadine SR matching placebo tablets BID orally on Day 1 through Day 42 in the Double-blind Treatment Period.
All Cause Mortality
	Placebo: SB Run-in Period Only		Placebo + Centanafadine SR 200 mg		Placebo + Centanafadine SR 400 mg		Placebo + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/138 (0%)		0/149 (0%)		0/149 (0%)		0/148 (0%)
Serious Adverse Events
	Placebo: SB Run-in Period Only		Placebo + Centanafadine SR 200 mg		Placebo + Centanafadine SR 400 mg		Placebo + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/138 (0%)		2/149 (1.3%)		0/149 (0%)		0/148 (0%)
Infections and infestations
Gastroenteritis viral	0/138 (0%)		1/149 (0.7%)		0/149 (0%)		0/148 (0%)
Influenza	0/138 (0%)		1/149 (0.7%)		0/149 (0%)		0/148 (0%)
Pneumonia	0/138 (0%)		1/149 (0.7%)		0/149 (0%)		0/148 (0%)
Other (Not Including Serious) Adverse Events
	Placebo: SB Run-in Period Only		Placebo + Centanafadine SR 200 mg		Placebo + Centanafadine SR 400 mg		Placebo + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/138 (1.4%)		25/149 (16.8%)		22/149 (14.8%)		18/148 (12.2%)
Gastrointestinal disorders
Dry Mouth	0/138 (0%)		6/149 (4%)		9/149 (6%)		0/148 (0%)
Infections and infestations
Upper respiratory tract infection	0/138 (0%)		8/149 (5.4%)		1/149 (0.7%)		3/148 (2%)
Metabolism and nutrition disorders
Decreased appetite	0/138 (0%)		9/149 (6%)		11/149 (7.4%)		2/148 (1.4%)
Nervous system disorders
Headache	2/138 (1.4%)		5/149 (3.4%)		7/149 (4.7%)		14/148 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.