Trial Outcomes & Findings for The Safety and Efficacy of OPC-64005 in the Treatment of Adult Attention-deficit/Hyperactivity Disorder (NCT NCT03324581)

Last Updated: 2021-10-29

Results Overview

The investigator-administered CAARS-O:SV consists of 18 items based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). It includes a 9-item inattentive symptom subscale and a 9-item hyperactive and impulsive symptoms subscale. Each item is rated on a scale of 0 to 3 where 0=not at all, never; 1=just a little, once a while; 2=pretty much, often; and 3=very much, very frequently. The score for each subscale can range from 0 to 27. The total score is the sum of individual scores and can range from 0 to 54. Higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

239 participants

Primary outcome timeframe

Baseline, Day 56

Results posted on

2021-10-29

Participant Flow

Participants took part in the study at 26 sites in the United States from 09 November 2017 to 31 October 2018.

Participants with adult attention deficit hyperactivity disorder (ADHD) were randomized in 1:1:1 ratio into the titration period to receive OPC-64005, atomoxetine, and placebo. This was followed by the treatment period wherein the dose was escalated based on tolerability.

Participant milestones

Participant milestones
Measure	OPC-64005 During the titration period, participants received OPC-64005 two 10 milligram (mg) tablets, and one OPC-64005-matching placebo tablet along with two atomoxetine-matching placebo capsules, orally, once daily (QD), from Day 1 up to Day 4. During the treatment period, participants received OPC-64005 three 10 mg tablets, and two atomoxetine-matching placebo capsules, orally, QD, from Day 5 up to Day 56. The dose was reduced to 20 mg if the 30 mg dose in the treatment period was not tolerable.	Atomoxetine During the titration period, participants received atomoxetine one 40 mg capsule and one atomoxetine-matching placebo capsule along with three OPC-64005-matching placebo tablets, orally, QD, from Day 1 up to Day 4. During the treatment period, participants received two atomoxetine 40 mg capsules and three OPC-64005-matching placebo tablets, orally, QD, from Day 5 up to Day 56. The dose was reduced to 40 mg if the 80 mg dose in the treatment period was not tolerable.	Placebo Participants received three OPC-64005-matching placebo tablets and two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 56.
Overall Study STARTED	77	80	82
Overall Study COMPLETED	38	44	57
Overall Study NOT COMPLETED	39	36	25

Reasons for withdrawal

Reasons for withdrawal
Measure	OPC-64005 During the titration period, participants received OPC-64005 two 10 milligram (mg) tablets, and one OPC-64005-matching placebo tablet along with two atomoxetine-matching placebo capsules, orally, once daily (QD), from Day 1 up to Day 4. During the treatment period, participants received OPC-64005 three 10 mg tablets, and two atomoxetine-matching placebo capsules, orally, QD, from Day 5 up to Day 56. The dose was reduced to 20 mg if the 30 mg dose in the treatment period was not tolerable.	Atomoxetine During the titration period, participants received atomoxetine one 40 mg capsule and one atomoxetine-matching placebo capsule along with three OPC-64005-matching placebo tablets, orally, QD, from Day 1 up to Day 4. During the treatment period, participants received two atomoxetine 40 mg capsules and three OPC-64005-matching placebo tablets, orally, QD, from Day 5 up to Day 56. The dose was reduced to 40 mg if the 80 mg dose in the treatment period was not tolerable.	Placebo Participants received three OPC-64005-matching placebo tablets and two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 56.
Overall Study Adverse Event	18	11	7
Overall Study Lack of Efficacy	0	1	0
Overall Study Lost to Follow-up	5	3	6
Overall Study Non-Compliance With Investigational Medicinal Product (IMP)	2	2	0
Overall Study Physician Decision	0	1	2
Overall Study Protocol Deviation	8	9	4
Overall Study Withdrawal by Subject	6	8	6
Overall Study Day 56 Visit was 15 Days Out of the Visit Window	0	1	0

Baseline Characteristics

The Safety and Efficacy of OPC-64005 in the Treatment of Adult Attention-deficit/Hyperactivity Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OPC-64005 n=77 Participants During the titration period, participants received OPC-64005 two 10 mg tablets, and one OPC-64005-matching placebo tablet along with two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 4. During the treatment period, participants received OPC-64005 three 10 mg tablets, and two atomoxetine-matching placebo capsules, orally, QD, from Day 5 up to Day 56. The dose was reduced to 20 mg if the 30 mg dose in the treatment period was not tolerable.	Atomoxetine n=80 Participants During the titration period, participants received atomoxetine one 40 mg capsule and one atomoxetine-matching placebo capsule along with three OPC-64005-matching placebo tablets, orally, QD, from Day 1 up to Day 4. During the treatment period, participants received two atomoxetine 40 mg capsules and three OPC-64005-matching placebo tablets, orally, QD, from Day 5 up to Day 56. The dose was reduced to 40 mg if the 80 mg dose in the treatment period was not tolerable.	Placebo n=82 Participants Participants received three OPC-64005-matching placebo tablets and two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 56.	Total n=239 Participants Total of all reporting groups
Age, Continuous	35.8 years STANDARD_DEVIATION 8.6 • n=5 Participants	35.1 years STANDARD_DEVIATION 8.8 • n=7 Participants	34.6 years STANDARD_DEVIATION 9.3 • n=5 Participants	35.1 years STANDARD_DEVIATION 8.9 • n=4 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	46 Participants n=7 Participants	42 Participants n=5 Participants	127 Participants n=4 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	34 Participants n=7 Participants	40 Participants n=5 Participants	112 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	58 Participants n=5 Participants	60 Participants n=7 Participants	64 Participants n=5 Participants	182 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	7 Participants n=5 Participants	15 Participants n=7 Participants	12 Participants n=5 Participants	34 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	7 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	21 Participants n=5 Participants	18 Participants n=7 Participants	17 Participants n=5 Participants	56 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	55 Participants n=5 Participants	62 Participants n=7 Participants	65 Participants n=5 Participants	182 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Day 56

Population: Full Analysis Set (FAS) included all randomized participants who took at least one dose of IMP and had a Baseline and at least one post randomization evaluation for the CAARS-O:SV ADHD Symptoms total score (18-items). Number analyzed is the number of participants with data available for analysis at the given time point.

Outcome measures

Outcome measures
Measure	OPC-64005 n=76 Participants During the titration period, participants received OPC-64005 two 10 mg tablets, and one OPC-64005-matching placebo tablet along with two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 4. During the treatment period, participants received OPC-64005 three 10 mg tablets, and two atomoxetine-matching placebo capsules, orally, QD, from Day 5 up to Day 56. The dose was reduced to 20 mg if the 30 mg dose in the treatment period was not tolerable.	Atomoxetine n=74 Participants During the titration period, participants received atomoxetine one 40 mg capsule and one atomoxetine-matching placebo capsule along with three OPC-64005-matching placebo tablets, orally, QD, from Day 1 up to Day 4. During the treatment period, participants received two atomoxetine 40 mg capsules and three OPC-64005-matching placebo tablets, orally, QD, from Day 5 up to Day 56. The dose was reduced to 40 mg if the 80 mg dose in the treatment period was not tolerable.	Placebo n=77 Participants Participants received three OPC-64005-matching placebo tablets and two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 56.
Change From Baseline in Conners' Adult ADHD Rating Scales-Observer: Screening Version (CAARS-O:SV) 18-item ADHD Symptoms Total Score at Day 56 Baseline	40.71 score on a scale Standard Deviation 6.99	41.59 score on a scale Standard Deviation 6.66	40.51 score on a scale Standard Deviation 7.10
Change From Baseline in Conners' Adult ADHD Rating Scales-Observer: Screening Version (CAARS-O:SV) 18-item ADHD Symptoms Total Score at Day 56 Change at Day 56	-19.4 score on a scale Standard Deviation 17.79	-20.2 score on a scale Standard Deviation 13.24	-10.3 score on a scale Standard Deviation 13.52

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Days 7, 14, 21, 28, 42, and 56

The investigator-administered CAARS-O:SV consists of 18 items based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. It includes a 9-item inattentive symptom subscale and a 9- item hyperactive and impulsive symptoms subscale. Each item is rated on a scale of 0 to 3 where 0=not at all, never; 1=just a little, once a while; 2=pretty much, often; and 3=very much, very frequently. The score for each subscale can range from 0 to 27. The total score is the sum of individual scores and can range from 0 to 54. Higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Days 28 and 56

The AISRS consists of 18-items derived from DSM-IV criteria for ADHD symptoms. The AISRS total score is the sum of the 9-item inattentive symptoms subscale and 9-item hyperactive and impulsive symptoms subscale. Each item is scored as follows: 0=none, 1=mild, 2=moderate, and 3=severe. The score for each subscale can range from 0 to 27. The total score can range from 0 to 54. A negative change from Baseline indicates improvement.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Days 7, 14, 21, 28, 42, and 56

The CGI-S evaluates the severity of individual symptoms and treatment response in participants with mental disorders. It is a 7-point scale that that requires the clinician to rate the severity of the participant's illness at the time of assessment as 0=not assessed, 1=normal, not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill participants. The score 0=not assessed was set to missing. A negative change from Baseline indicates improvement.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Days 7, 14, 21, 28, 42, and 56

The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a Baseline state at the beginning of the intervention and rated as: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. The score of 0 =not assessed was set to missing. Lower scores indicate improvement.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Days 7, 14, 21, 28, 42, and 56

The CAARS-S:SV comprises of 30 items to measure symptoms for ADHD in adults but was limited to the 18 DSM-5 criteria relevant items for this trial. The 18-item ADHD Symptoms total score is the sum of the 9-item inattentive symptoms subscale and the 9-item hyperactive and impulsive symptoms subscale. Each item is rated on a scale of 0 to 3 where 0=not at all, never; 1=just a little, once a while; 2=pretty much, often; and 3=very much, very frequently. The score for each subscale can range from 0 to 27. Total score can range from 0 to 54. A negative change from Baseline indicates improvement.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Days 28, and 56

The AAQoL is a validated, 29-item instrument for measuring the impact of ADHD symptoms on quality of life. The scale assesses 4 distinct functional domains based on the following subscales: life productivity (11 items), psychological health (6 items), life outlook (7 items), and relationships (5 items). Scores for individual items range from 1=never/not at all to 5=extremely/very often. Total and subscale scores were computed by (1) reversing scores for all items except the seven items in the Life Outlook subscale; (2) transforming all item scores to a 0-100 point scale (1=0; 2=25; 3=50; 4=75; 5=100); and (3) summing item scores and dividing by the item count to generate subscale and total scores. Higher scores indicate a greater impact.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Days 7, 14, 21, 28, 42, and 56

The DEQ was used to assess the potential for abuse of OPC-64005. It is a 5-item questionnaire completed by the participant that includes the following questions: 1. Do you feel a drug effect right now? 2. Are you high right now? 3. Do you dislike any of the effects you are feeling right now? 4. Do you like any of the effects you are feeling right now? 5. would you like more of the drug you took, right now? Each item is rated on a 100-point scale of 1 (not at all) to 100 (extremely). 100 represents the highest score for that subjective state, and the higher the score, the worse the outcome.

Outcome measures

Outcome data not reported

Adverse Events

OPC-64005

Serious events: 1 serious events

Other events: 61 other events

Deaths: 0 deaths

Atomoxetine

Serious events: 0 serious events

Other events: 59 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OPC-64005 n=77 participants at risk During the titration period, participants received OPC-64005 two 10 mg tablets, and one OPC-64005-matching placebo tablet along with two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 4. During the treatment period, participants received OPC-64005 three 10 mg tablets, and two atomoxetine-matching placebo capsules, orally, QD, from Day 5 up to Day 56. The dose was reduced to 20 mg if the 30 mg dose in the treatment period was not tolerable.	Atomoxetine n=79 participants at risk During the titration period, participants received atomoxetine one 40 mg capsule and one atomoxetine-matching placebo capsule along with three OPC-64005-matching placebo tablets, orally, QD, from Day 1 up to Day 4. During the treatment period, participants received two atomoxetine 40 mg capsules and three OPC-64005-matching placebo tablets, orally, QD, from Day 5 up to Day 56. The dose was reduced to 40 mg if the 80 mg dose in the treatment period was not tolerable.	Placebo n=82 participants at risk Participants received three OPC-64005-matching placebo tablets and two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 56.
Psychiatric disorders Suicide attempt	1.3% 1/77 • From first dose up to 30 days post last dose of study drug (Up to approximately 12 months) Safety Analysis Set included all participants who were randomized and administered at least 1 dose of IMP during the trial.	0.00% 0/79 • From first dose up to 30 days post last dose of study drug (Up to approximately 12 months) Safety Analysis Set included all participants who were randomized and administered at least 1 dose of IMP during the trial.	0.00% 0/82 • From first dose up to 30 days post last dose of study drug (Up to approximately 12 months) Safety Analysis Set included all participants who were randomized and administered at least 1 dose of IMP during the trial.

Other adverse events

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