Adult Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD, ADD
Brief summary
A trial to assess the safety and efficacy of OPC-64005 in the treatment of adult attention-deficit/hyperactivity disorder.
Detailed description
A multicenter, randomized, double-blind, active- and placebo-controlled, parallel-design trial.
Interventions
DRUGOPC-64005
OPC-64005 film coated tablets
DRUGAtomoxetine
Atomoxetine gelatin capsules
DRUGPlacebo
OPC-64005-matching placebo film coated tablets and atomoxetine-matching placebo gelatin capsules
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
(Screening): * Male and female participants 18 to 55 years of age, inclusive, at the time of informed consent. * Participants with a primary Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnosis of ADHD (including predominantly inattentive presentation, hyperactive presentation, and combined presentations) as confirmed by the Adult ADHD Clinical Diagnostic Scale (ACDS) v 1.2. * Participants willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and up to the 30 (+ 2)-day follow-up period.
Exclusion criteria
* Participants with a history of inadequate response or suboptimal tolerability to atomoxetine. * Participants who report allergies (lifetime treatment history) to stimulant or nonstimulant ADHD medications. * Participants with other DSM-5 disorders including psychosis (current or lifetime), bipolar disorder (current or lifetime), current major depressive disorder, or current panic disorder; or another psychiatric diagnosis that the investigator believes is primary or that will confound efficacy or safety assessments of the trail or interfere with participation in the trial otherwise. * Participants with a clinically significant current DSM-5 diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, histrionic, narcissistic, avoidant, obsessive compulsive, or dependent personality disorders. * Participants who currently have clinically significant dermatological, neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders such as any history of myocardial infarction, congestive heart failure, HIV (human immunodeficiency virus) seropositive status/acquired immunodeficiency syndrome, or active or chronic hepatitis B or C. * Participants with a history of obstructive sleep apnea.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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, Day 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). 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CAARS-O:SV 18-item Score on Days 7, 14, 21, 28, 42, and 56 | 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. |
| Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) With Adult Prompts Score on Day 28 and Day 56 | 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. |
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score on Days 7, 14, 21, 28, 42, and 56 | 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. |
| Clinical Global Impression-Improvement (CGI-I) Score on Days 7, 14, 21, 28, 42, and 56 | 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. |
| Change From Baseline in Conners' Adult ADHD Rating Scales-Self-Report: Screening Version (CAARS-S:SV) 18-item Total Score on Days 7, 14, 21, 28, 42, and 56 | 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. |
| Change From Baseline in Adult ADHD Quality of Life Scale (AAQoL) Total Score on Day 28 and Day 56 | 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. |
| OPC-64005 Potential for Abuse Liability and Dependence as Assessed by the Drug Effects Questionnaire (DEQ) Score | 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. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 26 sites in the United States from 09 November 2017 to 31 October 2018.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| OPC-64005 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. | 77 |
| 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. | 80 |
| Placebo Participants received three OPC-64005-matching placebo tablets and two atomoxetine-matching placebo capsules, orally, QD, from Day 1 up to Day 56. | 82 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 18 | 11 | 7 |
| Overall Study | Day 56 Visit was 15 Days Out of the Visit Window | 0 | 1 | 0 |
| 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 |
Baseline characteristics
| Characteristic | Atomoxetine | Total | OPC-64005 | Placebo |
|---|---|---|---|---|
| Age, Continuous | 35.1 years STANDARD_DEVIATION 8.8 | 35.1 years STANDARD_DEVIATION 8.9 | 35.8 years STANDARD_DEVIATION 8.6 | 34.6 years STANDARD_DEVIATION 9.3 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 18 Participants | 56 Participants | 21 Participants | 17 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 62 Participants | 182 Participants | 55 Participants | 65 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 2 Participants | 7 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 5 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 15 Participants | 34 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 9 Participants | 7 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 60 Participants | 182 Participants | 58 Participants | 64 Participants |
| Sex: Female, Male Female | 46 Participants | 127 Participants | 39 Participants | 42 Participants |
| Sex: Female, Male Male | 34 Participants | 112 Participants | 38 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 79 | 0 / 82 |
| other Total, other adverse events | 61 / 77 | 59 / 79 | 38 / 82 |
| serious Total, serious adverse events | 1 / 77 | 0 / 79 | 0 / 82 |
Outcome results
Primary
Change From Baseline in Conners' Adult ADHD Rating Scales-Observer: Screening Version (CAARS-O:SV) 18-item ADHD Symptoms Total Score at Day 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). 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OPC-64005 | 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 |
| OPC-64005 | 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 |
| Atomoxetine | 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 | 41.59 score on a scale | Standard Deviation 6.66 |
| Atomoxetine | 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 | -20.2 score on a scale | Standard Deviation 13.24 |
| Placebo | 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 | 40.51 score on a scale | Standard Deviation 7.1 |
| Placebo | 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 | -10.3 score on a scale | Standard Deviation 13.52 |
p-value: =0.755495% CI: [-4.3, 5.92]Mixed-effect Model Repeated Measures
p-value: =0.010195% CI: [-11.6, -1.6]Mixed-effect Model Repeated Measures
p-value: =0.003395% CI: [-12.3, -2.5]Mixed-effect Model Repeated Measures
Other Pre-specified
Change From Baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) With Adult Prompts Score on Day 28 and Day 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.
Time frame: Baseline, Days 28 and 56
Other Pre-specified
Change From Baseline in Adult ADHD Quality of Life Scale (AAQoL) Total Score on Day 28 and Day 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.
Time frame: Baseline, Days 28, and 56
Other Pre-specified
Change From Baseline in CAARS-O:SV 18-item Score on 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.
Time frame: Baseline, Days 7, 14, 21, 28, 42, and 56
Other Pre-specified
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score on 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.
Time frame: Baseline, Days 7, 14, 21, 28, 42, and 56
Other Pre-specified
Change From Baseline in Conners' Adult ADHD Rating Scales-Self-Report: Screening Version (CAARS-S:SV) 18-item Total Score on 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.
Time frame: Baseline, Days 7, 14, 21, 28, 42, and 56
Other Pre-specified
Clinical Global Impression-Improvement (CGI-I) Score on 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.
Time frame: Baseline, Days 7, 14, 21, 28, 42, and 56
Other Pre-specified
OPC-64005 Potential for Abuse Liability and Dependence as Assessed by the Drug Effects Questionnaire (DEQ) Score
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.
Time frame: Baseline, Days 7, 14, 21, 28, 42, and 56