Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD
Brief summary
With the pharmacokinetics (PK) of centanafadine currently being evaluated in adults. The PK of extended-release centanafadine may differ in children compared to adults due to physiological differences in the gastrointestinal tract. The information in this trial will support pediatric dose selection in future trials.
Interventions
DRUGCentanafadine
Extended-release and immediate-release capsules.
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All the participants received only centanafadine but divided into 2 arm groups based on administration (as capsules or drug sprinkled onto applesauce).
Eligibility
Sex/Gender
ALL
Age
9 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent obtained from a legally acceptable representative and assent obtained from the participant prior to the initiation of any trial-related procedures. * Male or female participants 9 to 12 years of age, inclusive, at the time of informed consent. * Participants with documented history of ADHD and confirmation of an ADHD prescription medication. * Participant is judged by the investigator to be clinically stable and has not had any psychiatric hospitalizations within the past 12 weeks.
Exclusion criteria
* Participants with a history of intellectual disability as determined by at least 1 of the following: intelligence quotient (IQ) \< 70, or clinical evidence, or a social or school history that is suggestive of an intellectual disability. * Participants who have any of the following: * Significant risk of committing suicide based on history * Current suicidal behavior * Imminent risk of injury to self * Active suicidal ideation * Any lifetime history of suicidal behavior detected by the Baseline/Screening version of the Columbia-Suicide Severity Rating Scale (C-SSRS). * Participants with a lifetime history of a substance use disorder (as determined by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition \[DSM-5\] criteria), or current substance misuse including alcohol and benzodiazepines, but excluding caffeine and nicotine. * Participants with hypothyroidism or hyperthyroidism or an abnormal result for free thyroxine (T4) at screening. * Participants who currently have clinically significant neurological, dermatological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders. * Participants with insulin-dependent diabetes mellitus. * Participants with epilepsy or a history of seizures or a history of severe head trauma or cerebrovascular disease. * Any major surgery within 30 days prior to dosing with the investigational medicinal product (IMP). * Any history of significant bleeding or hemorrhagic tendencies. * Blood transfusion within 30 days prior to dosing with IMP. * Participants with a positive drug screen for cocaine, marijuana (even if by prescription), or other illicit drugs, or alcohol, are excluded and may not be retested or rescreened. * Participants who have a supine or standing diastolic blood pressure, after resting for at least 5 minutes ≥ 95 mmHg. * Participants who participated in a clinical trial and were exposed to IMP within the last 30 days prior to screening or who participated in more than 2 interventional clinical trials within the past year. * Participants with a history of true allergic response to a medication or a history of dermatologic adverse reactions or anaphylaxis secondary to drug exposure. * Participants who do not tolerate venipuncture or have poor venous access that would cause difficulty when collecting blood samples. * Relatives of the trial site employees cannot participate in the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Centanafadine | 1, 2, 3, 4, 6, 8, 10,12 hours post dose on Day 1 and 22-26 hours post dose on Day 2 |
| PK Parameter: Time to Maximum Plasma Concentration (Tmax) of Centanafadine | 1, 2, 3, 4, 6, 8, 10,12 hours post dose on Day 1 and 22-26 hours post dose on Day 2 |
| PK Parameter: Area Under Concentration-time Curve From Time 0 to 12 Hours Postdose (AUC0-12h) of Centanafadine | 0 to 12 hours post dose on Day 1 |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 2 investigative sites in the United States from 07 October 2019 to 21 December 2019.
Pre-assignment details
A total of 20 participants were screened and 13 participants were enrolled in the study to receive centanafadine as capsules or sprinkled onto applesauce.
Participants by arm
| Arm | Count |
|---|---|
| Swallowed Capsules Cohort Participants swallowed two capsules of centanafadine (one containing a 50-milligram \[mg\] dose as extended release beads and other containing a 5-mg dose as immediate-release \[IR\] beads), total dose of 55 mg, orally in the morning of Day 1 following a minimum 8-hour fast. | 7 |
| Sprinkled Onto Applesauce Cohort Participants were administered centanafadine 55 mg, contents of 2 capsules (one containing a 50-mg dose as beads and other containing a 5-mg dose as IR beads) sprinkled on a tablespoon of applesauce, orally in the morning of Day 1 following a minimum 8-hour fast. | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sprinkled Onto Applesauce Cohort | Total | Swallowed Capsules Cohort |
|---|---|---|---|
| Age, Continuous | 10.5 years STANDARD_DEVIATION 1.4 | 10.5 years STANDARD_DEVIATION 1.1 | 10.6 years STANDARD_DEVIATION 1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 10 Participants | 6 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 9 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 1 / 7 | 0 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Centanafadine
Time frame: 1, 2, 3, 4, 6, 8, 10,12 hours post dose on Day 1 and 22-26 hours post dose on Day 2
Population: Pharmacokinetic (PK) analysis set included all participants who received the single dose of centanafadine and had at least 1 postdose evaluable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Swallowed Capsules Cohort | Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Centanafadine | 153 nanograms per milliliter (ng/mL) | Standard Deviation 51.4 |
| Sprinkled Onto Applesauce Cohort | Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Centanafadine | 129 nanograms per milliliter (ng/mL) | Standard Deviation 52.8 |
Primary
PK Parameter: Area Under Concentration-time Curve From Time 0 to 12 Hours Postdose (AUC0-12h) of Centanafadine
Time frame: 0 to 12 hours post dose on Day 1
Population: PK analysis set included all participants who received the single dose of centanafadine and had at least 1 postdose evaluable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Swallowed Capsules Cohort | PK Parameter: Area Under Concentration-time Curve From Time 0 to 12 Hours Postdose (AUC0-12h) of Centanafadine | 962 h*ng/mL | Standard Deviation 320 |
| Sprinkled Onto Applesauce Cohort | PK Parameter: Area Under Concentration-time Curve From Time 0 to 12 Hours Postdose (AUC0-12h) of Centanafadine | 828 h*ng/mL | Standard Deviation 346 |
Primary
PK Parameter: Time to Maximum Plasma Concentration (Tmax) of Centanafadine
Time frame: 1, 2, 3, 4, 6, 8, 10,12 hours post dose on Day 1 and 22-26 hours post dose on Day 2
Population: PK analysis set included all participants who received the single dose of centanafadine and had at least 1 postdose evaluable plasma concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Swallowed Capsules Cohort | PK Parameter: Time to Maximum Plasma Concentration (Tmax) of Centanafadine | 3.03 hours (h) |
| Sprinkled Onto Applesauce Cohort | PK Parameter: Time to Maximum Plasma Concentration (Tmax) of Centanafadine | 2.58 hours (h) |