Trial Outcomes & Findings for A Trial to Evaluate the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder (NCT NCT03605836)

Last Updated: 2021-10-18

Results Overview

The 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). Mixed-effect model repeated measure (MMRM) was used for the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

590 participants

Primary outcome timeframe

Baseline and Day 42

Results posted on

2021-10-18

Participant Flow

Participants took part in the study at 48 investigative sites in the United States from 16 January 2019 to 14 May 2020.

A total of 590 participants were enrolled in the study, out of which 579 started the Single-blind Placebo Run-in Period. Out of 579, 440 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 Run-in Period: Placebo Placebo-matching tablets twice daily (BID) 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 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.	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 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 Adult ADHD Self Report Scale (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.
OL Placebo Run-in Period [1 Week] STARTED	590	0	0	0
OL Placebo Run-in Period [1 Week] Treated	579	0	0	0
OL Placebo Run-in Period [1 Week] COMPLETED	440	0	0	0
OL Placebo Run-in Period [1 Week] NOT COMPLETED	150	0	0	0
Double-blind Treatment Period [6 Weeks] STARTED	0	147	147	146
Double-blind Treatment Period [6 Weeks] Treated	0	145	143	142
Double-blind Treatment Period [6 Weeks] COMPLETED	0	111	102	123
Double-blind Treatment Period [6 Weeks] NOT COMPLETED	0	36	45	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Single-blind Run-in Period: Placebo Placebo-matching tablets twice daily (BID) 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 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.	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 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 Adult ADHD Self Report Scale (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.
OL Placebo Run-in Period [1 Week] Adverse Event	2	0	0	0
OL Placebo Run-in Period [1 Week] Lack of Efficacy	2	0	0	0
OL Placebo Run-in Period [1 Week] Lost to Follow-up	8	0	0	0
OL Placebo Run-in Period [1 Week] Non-Compliance With Study Drug	4	0	0	0
OL Placebo Run-in Period [1 Week] Protocol Deviation	4	0	0	0
OL Placebo Run-in Period [1 Week] Withdrawal by Subject	17	0	0	0
OL Placebo Run-in Period [1 Week] Site Terminated by Sponsor	5	0	0	0
OL Placebo Run-in Period [1 Week] Physician Decision	7	0	0	0
OL Placebo Run-in Period [1 Week] Reason not Related to COVID-19	85	0	0	0
OL Placebo Run-in Period [1 Week] COVID-19 Related	15	0	0	0
OL Placebo Run-in Period [1 Week] Discontinued Prior to the Treatment.	1	0	0	0
Double-blind Treatment Period [6 Weeks] Randomized but Not Treated in Double-Blind Treatment Period	0	2	4	4
Double-blind Treatment Period [6 Weeks] Adverse Event	0	5	8	0
Double-blind Treatment Period [6 Weeks] Lack of Efficacy	0	0	2	1
Double-blind Treatment Period [6 Weeks] Lost to Follow-up	0	3	5	1
Double-blind Treatment Period [6 Weeks] Non-compliance with Study Drug	0	1	0	4
Double-blind Treatment Period [6 Weeks] Pregnancy	0	1	0	0
Double-blind Treatment Period [6 Weeks] Protocol Deviation	0	5	1	1
Double-blind Treatment Period [6 Weeks] Withdrawal by Subject	0	10	6	4
Double-blind Treatment Period [6 Weeks] Physician Decision	0	3	1	0
Double-blind Treatment Period [6 Weeks] Reason not Specified	0	6	16	7
Double-blind Treatment Period [6 Weeks] Covid-19 Related	0	0	2	1

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=150 Participants 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.	Double-blind Treatment Period: Placebo + Centanafadine SR 200 mg n=147 Participants 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.	Double-blind Treatment Period: Placebo + Centanafadine SR 400 mg n=147 Participants 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.	Double-blind Treatment Period: Placebo + Placebo n=146 Participants 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.	Total n=590 Participants Total of all reporting groups
Age, Continuous	33.7 years STANDARD_DEVIATION 9.6 • n=150 Participants	34.5 years STANDARD_DEVIATION 9.7 • n=147 Participants	35.2 years STANDARD_DEVIATION 10.4 • n=147 Participants	35.2 years STANDARD_DEVIATION 9.6 • n=146 Participants	34.6 years STANDARD_DEVIATION 9.8 • n=590 Participants
Sex: Female, Male Female	70 Participants n=150 Participants	71 Participants n=147 Participants	70 Participants n=147 Participants	66 Participants n=146 Participants	277 Participants n=590 Participants
Sex: Female, Male Male	80 Participants n=150 Participants	76 Participants n=147 Participants	77 Participants n=147 Participants	80 Participants n=146 Participants	313 Participants n=590 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	30 Participants n=150 Participants	27 Participants n=147 Participants	23 Participants n=147 Participants	29 Participants n=146 Participants	109 Participants n=590 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	119 Participants n=150 Participants	117 Participants n=147 Participants	122 Participants n=147 Participants	116 Participants n=146 Participants	474 Participants n=590 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=150 Participants	3 Participants n=147 Participants	2 Participants n=147 Participants	1 Participants n=146 Participants	7 Participants n=590 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=150 Participants	0 Participants n=147 Participants	2 Participants n=147 Participants	2 Participants n=146 Participants	4 Participants n=590 Participants
Race (NIH/OMB) Asian	4 Participants n=150 Participants	10 Participants n=147 Participants	2 Participants n=147 Participants	6 Participants n=146 Participants	22 Participants n=590 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=150 Participants	1 Participants n=147 Participants	0 Participants n=147 Participants	0 Participants n=146 Participants	2 Participants n=590 Participants
Race (NIH/OMB) Black or African American	26 Participants n=150 Participants	17 Participants n=147 Participants	19 Participants n=147 Participants	21 Participants n=146 Participants	83 Participants n=590 Participants
Race (NIH/OMB) White	116 Participants n=150 Participants	112 Participants n=147 Participants	120 Participants n=147 Participants	114 Participants n=146 Participants	462 Participants n=590 Participants
Race (NIH/OMB) More than one race	0 Participants n=150 Participants	0 Participants n=147 Participants	0 Participants n=147 Participants	0 Participants n=146 Participants	0 Participants n=590 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=150 Participants	7 Participants n=147 Participants	4 Participants n=147 Participants	3 Participants n=146 Participants	17 Participants n=590 Participants
Adult Attention-deficit/Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale(AISRS) Score	—	37.6 score on a scale STANDARD_DEVIATION 6.7 • n=147 Participants • Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.	38.6 score on a scale STANDARD_DEVIATION 7.0 • n=147 Participants • Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.	37.8 score on a scale STANDARD_DEVIATION 6.5 • n=146 Participants • Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.	38.0 score on a scale STANDARD_DEVIATION 6.7 • n=440 Participants • Data for ADHD AISRS scale was collected only for Double-blind Treatment Period arms.
Clinical Global Impression-Severity of Illness Scale (CGI-S) Score	—	4.6 score on a scale STANDARD_DEVIATION 0.6 • n=147 Participants • Data for CGI-S scale was collected only for Double-blind Treatment Period arms.	4.6 score on a scale STANDARD_DEVIATION 0.5 • n=147 Participants • Data for CGI-S scale was collected only for Double-blind Treatment Period arms.	4.5 score on a scale STANDARD_DEVIATION 0.6 • n=146 Participants • Data for CGI-S scale was collected only for Double-blind Treatment Period arms.	4.6 score on a scale STANDARD_DEVIATION 0.6 • n=440 Participants • Data for CGI-S scale was collected only for Double-blind Treatment Period arms.

PRIMARY outcome

Timeframe: Baseline and Day 42

Population: Efficacy Sample FAS includes 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=140 Participants 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.	Double-blind Treatment Period: Centanafadine SR 400 mg n=140 Participants 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 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=141 Participants Following Single-blind Run-in Period, participants with \<30% improvement on Adult ADHD Self Report Scale (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) Score at Day 42	-12.1 score on a scale Standard Error 0.96	-12.5 score on a scale Standard Error 0.99	-8.07 score on a scale Standard Error 0.94

SECONDARY 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.

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=140 Participants 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.	Double-blind Treatment Period: Centanafadine SR 400 mg n=140 Participants 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 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=141 Participants Following Single-blind Run-in Period, participants with \<30% improvement on Adult ADHD Self Report Scale (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) Score at Day 42	-1.04 score on a scale Standard Error 0.09	-0.99 score on a scale Standard Error 0.09	-0.71 score on a scale Standard Error 0.09

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 59 days

Other events: 31 other events

Deaths: 0 deaths

Placebo + Centanafadine SR 400 mg

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

Placebo + Placebo

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo: Single-blind Run-in Period Only n=149 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=145 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=143 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=142 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 Bronchitis	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.	0.69% 1/145 • 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% 0/143 • 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% 0/142 • 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: Single-blind Run-in Period Only n=149 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=145 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=143 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=142 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 Diarrhoea	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.	2.8% 4/145 • 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.	5.6% 8/143 • 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.	2.1% 3/142 • 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.
Gastrointestinal disorders Dry Mouth	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.	2.1% 3/145 • 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.	6.3% 9/143 • 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.	0.70% 1/142 • 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.
Gastrointestinal disorders Nausea	2.0% 3/149 • 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.	3.4% 5/145 • 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.	10.5% 15/143 • 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.	2.1% 3/142 • 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	0.67% 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.	6.2% 9/145 • 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.	3.5% 5/143 • 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.	3.5% 5/142 • 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 Apettite	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.	4.1% 6/145 • 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.	7.0% 10/143 • 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.	2.1% 3/142 • 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	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.	7.6% 11/145 • 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.	10.5% 15/143 • 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.	5.6% 8/142 • 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.
Psychiatric disorders Insomnia	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.	2.1% 3/145 • 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.	5.6% 8/143 • 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.	2.1% 3/142 • 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.
Publication restrictions are in place

Restriction type: OTHER