Trial Outcomes & Findings for A Trial Evaluating the Long-term Safety and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder (NCT NCT03605849)

Last Updated: 2024-10-01

Results Overview

An AE is defined as any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with an onset date on or after the first dose of IMP. They are all adverse events that started after the start of centanafadine; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption or reduction of study therapy. TEAEs were graded on a 3-point scale and the intensity of an adverse experience was defined as follows: 1 = Mild: Discomfort noticed, but no disruption to daily activity, 2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity, and 3 = Severe: Inability to work or perform normal daily activity.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

662 participants

Primary outcome timeframe

From first dose of study drug up to 30 days after last dose of study drug (Up to approximately Week 56)

Results posted on

2024-10-01

Participant Flow

This study was conducted in the United States from 14 February 2019 to 07 September 2021. A total of 662 participants were enrolled in the study. Out of 662 participants, 653 participants received the study treatment.

A total of 662 participants were treated in this study, 494 participants from parent studies (405-201-00013 and 405-201-00014) \&168 new participants joined in this current study. As pre-specified in Statistical analysis plan (SAP) data was analyzed by the parent studies (405-201-00013 and 405-201-00014) treatment groups for rollover participants and centanafadine SR 400mg for denovo participants. Data from the 2 parent studies was analyzed and reported in combined way for rollover participants.

Participant milestones

Participant milestones
Measure	Prior Centanafadine SR 200 mg Participants who received centanafadine sustained release (SR) 200 milligrams (mg) in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received a total daily dose (TDD) of centanafadine SR 400 mg in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, twice daily (BID) at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Centanafadine SR 400 mg Participants who received centanafadine SR 400 mg in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Placebo Participants who received placebo in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	De Novo Centanafadine SR 400 mg Participants who did not participate in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], and who were eligible for this study received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.
Overall Study STARTED	156	151	187	168
Overall Study Safety Sample	154	149	184	166
Overall Study COMPLETED	78	72	92	103
Overall Study NOT COMPLETED	78	79	95	65

Reasons for withdrawal

Reasons for withdrawal
Measure	Prior Centanafadine SR 200 mg Participants who received centanafadine sustained release (SR) 200 milligrams (mg) in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received a total daily dose (TDD) of centanafadine SR 400 mg in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, twice daily (BID) at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Centanafadine SR 400 mg Participants who received centanafadine SR 400 mg in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Placebo Participants who received placebo in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	De Novo Centanafadine SR 400 mg Participants who did not participate in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], and who were eligible for this study received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.
Overall Study Adverse Event	20	21	29	11
Overall Study Lack of Efficacy	4	7	9	2
Overall Study Lost to Follow-up	8	8	14	11
Overall Study Non-compliance With IMP	6	5	2	1
Overall Study Protocol Deviation	1	2	1	3
Overall Study Withdrawal by Subject	33	28	30	28
Overall Study Site Terminated by Sponsor	0	0	0	1
Overall Study Physician Decision	2	1	2	1
Overall Study Enrolled, but not Treated	2	2	3	2
Overall Study Other (COVID-19 Related)	0	1	1	0
Overall Study Other (Not Related to COVID-19)	2	4	4	5

Baseline Characteristics

A Trial Evaluating the Long-term Safety and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prior Centanafadine SR 200 mg n=156 Participants Participants who received centanafadine SR 200 mg in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received TDD of centanafadine SR 400 mg in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7 , followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Centanafadine SR 400 mg n=151 Participants Participants who received centanafadine SR 400 mg in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Placebo n=187 Participants Participants who received placebo in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	De Novo Centanafadine SR 400 mg n=168 Participants Participants who did not participate in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], and who were eligible for this study received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Total n=662 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	156 Participants n=99 Participants	151 Participants n=107 Participants	187 Participants n=206 Participants	168 Participants n=7 Participants	662 Participants n=31 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Sex/Gender, Customized Female	76 Participants n=99 Participants	76 Participants n=107 Participants	94 Participants n=206 Participants	92 Participants n=7 Participants	338 Participants n=31 Participants
Sex/Gender, Customized Male	80 Participants n=99 Participants	75 Participants n=107 Participants	93 Participants n=206 Participants	75 Participants n=7 Participants	323 Participants n=31 Participants
Sex/Gender, Customized Unknown	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants
Race/Ethnicity, Customized Race · White	121 Participants n=99 Participants	122 Participants n=107 Participants	162 Participants n=206 Participants	144 Participants n=7 Participants	549 Participants n=31 Participants
Race/Ethnicity, Customized Race · Black or African American	19 Participants n=99 Participants	21 Participants n=107 Participants	16 Participants n=206 Participants	10 Participants n=7 Participants	66 Participants n=31 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	4 Participants n=31 Participants
Race/Ethnicity, Customized Race · Asian	7 Participants n=99 Participants	1 Participants n=107 Participants	6 Participants n=206 Participants	9 Participants n=7 Participants	23 Participants n=31 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants
Race/Ethnicity, Customized Race · Other	8 Participants n=99 Participants	5 Participants n=107 Participants	2 Participants n=206 Participants	3 Participants n=7 Participants	18 Participants n=31 Participants
Race/Ethnicity, Customized Race · Unknown	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	34 Participants n=99 Participants	36 Participants n=107 Participants	35 Participants n=206 Participants	50 Participants n=7 Participants	155 Participants n=31 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	119 Participants n=99 Participants	112 Participants n=107 Participants	150 Participants n=206 Participants	116 Participants n=7 Participants	497 Participants n=31 Participants
Race/Ethnicity, Customized Ethnicity · Other	3 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	1 Participants n=7 Participants	7 Participants n=31 Participants
Race/Ethnicity, Customized Ethnicity · Unknown	0 Participants n=99 Participants	2 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	3 Participants n=31 Participants
Region of Enrollment United States	156 participants n=99 Participants	151 participants n=107 Participants	187 participants n=206 Participants	168 participants n=7 Participants	662 participants n=31 Participants

PRIMARY outcome

Timeframe: From first dose of study drug up to 30 days after last dose of study drug (Up to approximately Week 56)

Population: Safety Sample comprised all participants who received at least 1 dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.

Outcome measures

Outcome measures
Measure	Prior Centanafadine SR 200 mg n=154 Participants Participants who received centanafadine SR 200 mg in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Centanafadine SR 400 mg n=149 Participants Participants who received centanafadine SR 400 mg in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Placebo n=184 Participants Participants who received placebo in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	De Novo Centanafadine SR 400 mg n=166 Participants Participants who did not participate in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], and who were eligible for this study received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded by Severity Participants With TEAEs	98 Participants	89 Participants	123 Participants	91 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded by Severity Participants With Mild TEAE	73 Participants	59 Participants	92 Participants	70 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded by Severity Participants With Moderate TEAE	58 Participants	53 Participants	75 Participants	50 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded by Severity Participants With Severe TEAE	2 Participants	4 Participants	7 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 weeks or early termination

18-item scale with a total score range of 0 to 54 points. Composed of 2 subscales that can range from 0 to 27 points. A higher value represents a worse outcome. Efficacy endpoint. Results will be assessed to determine effectiveness of drug.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 weeks or early termination

An observer-rated scale with a total score range of 0 to 7. A higher score represents a worse outcome.Efficacy endpoint. Results will be assessed to determine effectiveness of drug.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 weeks or early termination

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.

Outcome measures

Outcome data not reported

Adverse Events

Prior Centanafadine SR 200 mg

Serious events: 1 serious events

Other events: 59 other events

Deaths: 0 deaths

Prior Centanafadine SR 400 mg

Serious events: 1 serious events

Other events: 49 other events

Deaths: 0 deaths

Prior Placebo

Serious events: 7 serious events

Other events: 81 other events

Deaths: 0 deaths

De Novo Centanafadine SR 400 mg

Serious events: 3 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Prior Centanafadine SR 200 mg n=154 participants at risk Participants who received centanafadine SR 200 mg in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Centanafadine SR 400 mg n=149 participants at risk Participants who received centanafadine SR 400 mg in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	Prior Placebo n=184 participants at risk Participants who received placebo in the parent double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.	De Novo Centanafadine SR 400 mg n=166 participants at risk Participants who did not participate in the parents double-blind phase 3 studies 405-201-00013 \[NCT03605680\] or 405-201-00014 \[NCT03605836\], and who were eligible for this study received centanafadine SR 400 mg TDD in current study, following a dose-escalation schedule. In the current study, participants received centanafadine SR tablets, orally, BID at a starting dose of 200 mg TDD on Day 1 through Day 7, followed by dose-escalation to 400 mg TDD from Day 8 up to Week 52.
Gastrointestinal disorders Diarrhoea	7.1% 11/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	4.0% 6/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	7.1% 13/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	9.6% 16/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
Gastrointestinal disorders Dry Mouth	4.5% 7/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	4.0% 6/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	6.5% 12/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	1.8% 3/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
Gastrointestinal disorders Nausea	7.1% 11/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	4.7% 7/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	10.3% 19/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	7.8% 13/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
General disorders Fatigue	4.5% 7/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	2.7% 4/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	3.3% 6/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	5.4% 9/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
Infections and infestations Nasopharyngitis	5.2% 8/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	3.4% 5/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	8.7% 16/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	2.4% 4/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
Infections and infestations Upper Respiratory Tract Infection	3.9% 6/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	4.7% 7/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	6.0% 11/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	3.0% 5/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
Metabolism and nutrition disorders Decreased Appetite	3.9% 6/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	4.7% 7/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	8.7% 16/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	8.4% 14/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
Nervous system disorders Headache	4.5% 7/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	7.4% 11/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	7.6% 14/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	8.4% 14/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
Psychiatric disorders Anxiety	5.2% 8/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	4.0% 6/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	6.5% 12/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	6.6% 11/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.
Psychiatric disorders Insomnia	5.8% 9/154 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	6.7% 10/149 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	10.3% 19/184 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.	8.4% 14/166 • From first dose through 30 days after last dose of study drug (Up to approximately Week 56) Safety Sample comprised of participants who received at least one dose of IMP. As prespecified in the SAP, data was analyzed based on the treatments (centanafadine SR 200mg, 400 mg or placebo) received by the participants in the parent double-blind phase 3 trials (405-201-00013 or 405-201-00014), and the centanafadine SR 400 mg received by de novo participants during this current study. Data from 2 parent studies was analyzed and reported in a combined way for rollover participants.

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: [email protected]

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.
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Restriction type: OTHER