Trial Outcomes & Findings for A Trial Evaluating the Efficacy, Safety, & Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder (NCT NCT03605680)

Last Updated: 2022-03-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

604 participants

Primary outcome timeframe

Baseline and Day 42

Results posted on

2022-03-15

Participant Flow

Participants took part in the study at 45 investigative sites in the United States from 16 January 2019 to 11 April 2020.

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.

Participant milestones

Participant milestones
Measure	Single-blind (SB) Run-in Period: Placebo Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1).	Double-blind Treatment Period: Centanafadine SR 200 mg 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.	Double-blind Treatment Period: Centanafadine SR 400 mg 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.	Double-blind Treatment Period: Placebo 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.
SB Placebo Run-in Period (1 Week) STARTED	604	0	0	0
SB Placebo Run-in Period (1 Week) Treated	584	0	0	0
SB Placebo Run-in Period (1 Week) COMPLETED	466	0	0	0
SB Placebo Run-in Period (1 Week) NOT COMPLETED	138	0	0	0
Double-blind Treatment Period (6 Weeks) STARTED	0	154	156	156
Double-blind Treatment Period (6 Weeks) COMPLETED	0	110	117	121
Double-blind Treatment Period (6 Weeks) NOT COMPLETED	0	44	39	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Single-blind (SB) Run-in Period: Placebo Placebo-matching tablets BID (twice daily) on Day -7 through Baseline (Day -1).	Double-blind Treatment Period: Centanafadine SR 200 mg 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.	Double-blind Treatment Period: Centanafadine SR 400 mg 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.	Double-blind Treatment Period: Placebo 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.
SB Placebo Run-in Period (1 Week) Adverse Event	6	0	0	0
SB Placebo Run-in Period (1 Week) Lack of Efficacy	1	0	0	0
SB Placebo Run-in Period (1 Week) Lost to Follow-up	9	0	0	0
SB Placebo Run-in Period (1 Week) Non-compliance With Study Drug	3	0	0	0
SB Placebo Run-in Period (1 Week) Protocol Deviation	13	0	0	0
SB Placebo Run-in Period (1 Week) Withdrawal by Subject	12	0	0	0
SB Placebo Run-in Period (1 Week) Site Terminated by Sponsor	1	0	0	0
SB Placebo Run-in Period (1 Week) Physician Decision	6	0	0	0
SB Placebo Run-in Period (1 Week) Reason not Specified	87	0	0	0
Double-blind Treatment Period (6 Weeks) Randomized but Not Treated in Double-Blind Treatment Period	0	5	7	8
Double-blind Treatment Period (6 Weeks) Adverse Event	0	8	8	3
Double-blind Treatment Period (6 Weeks) Lack of Efficacy	0	0	0	1
Double-blind Treatment Period (6 Weeks) Lost to Follow-up	0	3	4	3
Double-blind Treatment Period (6 Weeks) Non-compliance with Study Drug	0	3	1	2
Double-blind Treatment Period (6 Weeks) Protocol Deviation	0	14	7	5
Double-blind Treatment Period (6 Weeks) Withdrawal by Subject	0	4	4	7
Double-blind Treatment Period (6 Weeks) Physician Decision	0	1	2	0
Double-blind Treatment Period (6 Weeks) Reason not Specified	0	5	4	3
Double-blind Treatment Period (6 Weeks) Reason due to COVID-19	0	1	2	3

Baseline Characteristics

Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo: Single-blind Run-in Period Only n=138 Participants 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.	Double-blind Treatment Period: Placebo + Centanafadine SR 200 mg n=154 Participants 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.	Double-blind Treatment Period: Placebo + Centanafadine SR 400 mg n=156 Participants 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.	Double-blind Treatment Period: Placebo + Placebo n=156 Participants 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 n=604 Participants Total of all reporting groups
Age, Continuous	33.1 years STANDARD_DEVIATION 9.4 • n=138 Participants	36.6 years STANDARD_DEVIATION 9.8 • n=154 Participants	35.3 years STANDARD_DEVIATION 10.4 • n=156 Participants	35.0 years STANDARD_DEVIATION 9.9 • n=156 Participants	35.0 years STANDARD_DEVIATION 9.9 • n=604 Participants
Sex: Female, Male Female	57 Participants n=138 Participants	76 Participants n=154 Participants	75 Participants n=156 Participants	76 Participants n=156 Participants	284 Participants n=604 Participants
Sex: Female, Male Male	81 Participants n=138 Participants	78 Participants n=154 Participants	81 Participants n=156 Participants	80 Participants n=156 Participants	320 Participants n=604 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=138 Participants	34 Participants n=154 Participants	38 Participants n=156 Participants	29 Participants n=156 Participants	129 Participants n=604 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	110 Participants n=138 Participants	119 Participants n=154 Participants	116 Participants n=156 Participants	124 Participants n=156 Participants	469 Participants n=604 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=138 Participants	1 Participants n=154 Participants	2 Participants n=156 Participants	3 Participants n=156 Participants	6 Participants n=604 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=138 Participants	0 Participants n=154 Participants	3 Participants n=156 Participants	0 Participants n=156 Participants	4 Participants n=604 Participants
Race (NIH/OMB) Asian	5 Participants n=138 Participants	4 Participants n=154 Participants	2 Participants n=156 Participants	4 Participants n=156 Participants	15 Participants n=604 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=138 Participants	1 Participants n=154 Participants	1 Participants n=156 Participants	0 Participants n=156 Participants	3 Participants n=604 Participants
Race (NIH/OMB) Black or African American	22 Participants n=138 Participants	19 Participants n=154 Participants	23 Participants n=156 Participants	21 Participants n=156 Participants	85 Participants n=604 Participants
Race (NIH/OMB) White	107 Participants n=138 Participants	126 Participants n=154 Participants	123 Participants n=156 Participants	130 Participants n=156 Participants	486 Participants n=604 Participants
Race (NIH/OMB) More than one race	0 Participants n=138 Participants	0 Participants n=154 Participants	0 Participants n=156 Participants	0 Participants n=156 Participants	0 Participants n=604 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=138 Participants	4 Participants n=154 Participants	4 Participants n=156 Participants	1 Participants n=156 Participants	11 Participants n=604 Participants
Adult Attention-deficit/Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS)	—	39.7 score on a scale STANDARD_DEVIATION 6.7 • n=154 Participants • Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.	39.4 score on a scale STANDARD_DEVIATION 6.8 • n=156 Participants • Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.	39.4 score on a scale STANDARD_DEVIATION 7.1 • n=156 Participants • Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.	39.5 score on a scale STANDARD_DEVIATION 6.8 • n=466 Participants • Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.
Clinical Global Impression-Severity of Illness Scale (CGI-S)	—	4.5 score on a scale STANDARD_DEVIATION 0.6 • n=153 Participants • Data for CGI-S scale was collected only for Double-blind Treatment Period arms. Number analyzed is the number of participants with data available for analyses.	4.5 score on a scale STANDARD_DEVIATION 0.6 • n=156 Participants • Data for CGI-S scale was collected only for Double-blind Treatment Period arms. Number analyzed is the number of participants with data available for analyses.	4.5 score on a scale STANDARD_DEVIATION 0.6 • n=156 Participants • Data for CGI-S scale was collected only for Double-blind Treatment Period arms. Number analyzed is the number of participants with data available for analyses.	4.5 score on a scale STANDARD_DEVIATION 0.6 • n=465 Participants • Data for CGI-S scale was collected only for Double-blind Treatment Period arms. Number analyzed is the number of participants with data available for analyses.

PRIMARY outcome

Timeframe: Baseline and Day 42

Population: 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.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Centanafadine SR 200 mg n=147 Participants 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.	Double-blind Treatment Period: Centanafadine SR 400 mg n=147 Participants 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.	Double-blind Treatment Period: Placebo n=144 Participants 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.
Change From Baseline in ADHD Investigator Symptom Rating Scale (AISRS)	-10.1 score on a scale Standard Error 0.99	-9.73 score on a scale Standard Error 0.98	-6.98 score on a scale Standard Error 0.98

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Centanafadine SR 200 mg n=146 Participants 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.	Double-blind Treatment Period: Centanafadine SR 400 mg n=147 Participants 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.	Double-blind Treatment Period: Placebo n=144 Participants 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.
Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S)	-0.78 score on a scale Standard Error 0.09	-0.79 score on a scale Standard Error 0.08	-0.52 score on a scale Standard Error 0.08

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 59 days

Other events: 25 other events

Deaths: 0 deaths

Placebo + Centanafadine SR 400 mg

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo + Placebo

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo: SB Run-in Period Only n=138 participants at risk 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.	Placebo + Centanafadine SR 200 mg n=149 participants at risk 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.	Placebo + Centanafadine SR 400 mg n=149 participants at risk 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.	Placebo + Placebo n=148 participants at risk 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.
Infections and infestations Gastroenteritis viral	0.00% 0/138 • Up to 59 days 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.	0.67% 1/149 • Up to 59 days 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.	0.00% 0/149 • Up to 59 days 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.	0.00% 0/148 • Up to 59 days 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.
Infections and infestations Influenza	0.00% 0/138 • Up to 59 days 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.	0.67% 1/149 • Up to 59 days 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.	0.00% 0/149 • Up to 59 days 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.	0.00% 0/148 • Up to 59 days 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.
Infections and infestations Pneumonia	0.00% 0/138 • Up to 59 days 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.	0.67% 1/149 • Up to 59 days 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.	0.00% 0/149 • Up to 59 days 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.	0.00% 0/148 • Up to 59 days 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.

Other adverse events

Other adverse events
Measure	Placebo: SB Run-in Period Only n=138 participants at risk 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.	Placebo + Centanafadine SR 200 mg n=149 participants at risk 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.	Placebo + Centanafadine SR 400 mg n=149 participants at risk 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.	Placebo + Placebo n=148 participants at risk 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.
Gastrointestinal disorders Dry Mouth	0.00% 0/138 • Up to 59 days 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.	4.0% 6/149 • Up to 59 days 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.	6.0% 9/149 • Up to 59 days 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.	0.00% 0/148 • Up to 59 days 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.
Infections and infestations Upper respiratory tract infection	0.00% 0/138 • Up to 59 days 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.	5.4% 8/149 • Up to 59 days 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.	0.67% 1/149 • Up to 59 days 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.	2.0% 3/148 • Up to 59 days 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.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/138 • Up to 59 days 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.	6.0% 9/149 • Up to 59 days 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.	7.4% 11/149 • Up to 59 days 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.	1.4% 2/148 • Up to 59 days 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.
Nervous system disorders Headache	1.4% 2/138 • Up to 59 days 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.	3.4% 5/149 • Up to 59 days 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.	4.7% 7/149 • Up to 59 days 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.	9.5% 14/148 • Up to 59 days 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.

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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