ADHD
Conditions
Brief summary
This study is a multicenter, dose-optimized, open-label safety study with KP415 in children with Attention-Deficit/Hyperactivity Disorder (ADHD).
Detailed description
The study will consist of a Screening Period, a Dose Optimization Phase, and a Treatment Phase and a Follow-Up Visit, as follows: * Screening Period: Subjects will undergo a screening period up to 30 days prior to entering the Dose Optimization Phase. * Dose Optimization Phase: During the Dose Optimization Phase, subjects will be titrated to doses of 20, 30 or 40 mg KP415 based on tolerability and best individual dose-response in the opinion of the Investigator. * Treatment Phase: Eligible subjects will receive single daily doses of KP415 for up to approximately 360 days (up to approximately 12 months). The dose of KP415 given in the Treatment Phase will be the dose of KP415 at the end of the Dose Optimization Phase. During the Treatment Phase, the dose of KP415 may be changed based on individual tolerability and best dose response (to either 20, 30, or 40 mg KP415 capsules). Safety, efficacy and sleep behavior assessments will be performed. * Follow-Up Visit: 3 ±2 days after administration of the last dose of the Treatment Phase, subjects will enter a Follow-Up Visit to evaluate safety parameters.
Interventions
Once-daily oral dose
Sponsors
Zevra Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Subject must meet Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD (combined, inattentive, or hyperactive/impulsive presentation) per clinical evaluation and confirmed by the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). 2. Subject must have a score of at least 3 (mildly ill) on the clinician-administered Clinical Global Impressions-Severity (CGI-S) scale. 3. Subjects who completed the efficacy study with KP415 may be rolled over into the current study. 4. Subject, subject's parent/legal guardian and caregiver (if applicable) must understand and be willing and able to comply with all study procedures and visit schedule.
Exclusion criteria
1. Subject with any clinically significant chronic medical condition that may interfere with the participant's ability to participate in the study. 2. Subject has any diagnosis of bipolar I or II disorder, major depressive disorder, conduct disorder, obsessive-compulsive disorder, any history of psychosis, autism spectrum disorder, disruptive mood dysregulation disorder (DMDD), intellectual disability, Tourette's Syndrome, confirmed genetic disorder with cognitive and/or behavioral disturbances. 3. Subject has evidence of any chronic disease of the central nervous system (CNS) such as tumors, inflammation, seizure disorder, vascular disorder, potential CNS related disorders that might occur in childhood, or history of persistent neurological symptoms attributable to serious head injury. 4. Subject has a current (last month) psychiatric diagnosis other than specific phobia, motor skills disorders, oppositional defiant disorder, sleep disorders, elimination disorders, adjustment disorders, learning disorders, or communication disorders. Participants with school phobia or separation anxiety will not be eligible. 5. Subject has clinically significant suicidal ideation/behavior, based on a history of attempted suicide and the C-SSRS assessment at Screening or at any time before the last dose of study drug. 6. Subject has any clinically significant unstable medical abnormality, chronic disease, or a history of a clinically significant abnormality of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems, or a disorder or history of a condition that may interfere with drug absorption, distribution, metabolism, or excretion of study drug. 7. Subject has a history or presence of abnormal ECGs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With Treatment-Emergent Adverse Events (TEAEs) | Up to 12 months | TEAEs will be assessed starting following the first dose of study drug, and ending with the Follow-Up Visit or Early Termination Visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ADHD-RS-5 Total Score | Up to 12 months | The clinician-administered ADHD-RS-5 is an 18-item scale that rates ADHD symptoms on a 4-point scale. Each item is scored using a combination of severity and frequency ratings from a range of 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting severe symptoms or a frequency of very often), so that the total ADHD-RS-5 scores range from 0 to 54. The 18 items can be divided into two 9-item subscales: One for hyperactivity/impulsivity and the other for inattentiveness. |
| Change From Baseline in CGI-S | Up to 12 months | The CGI-S is a clinician-rated scale that evaluates the severity of psychopathology (ADHD symptoms in this study) on a scale from 1 (not at all ill) to 7 (among the most severely ill). |
| Change From Baseline in Children's Sleep Habits Questionnaire | Up to 12 months | The modified, abbreviated Children's Sleep Habits Questionnaire (CSHQ) will be used to assess the sleep behavior. The CSHQ is a retrospective, 33-item parent questionnaire to examine sleep behavior in small children. Items are rated on a 3-point scale of Usually, Sometimes and Rarely for occurrences in a number of key sleep domains: bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Scores range from 33-99, with higher scores represent more disturbed sleep. Scores were obtained during a clinician-directed interview with the parent/guardian/caregiver. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment Optimized dose of KP415 (serdexmethylphenidate \[SDX\] Cl/ d-methylphenidate \[d-MPH\] HCl) oral capsule:
28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl) | 238 |
| Total | 238 |
Baseline characteristics
| Characteristic | Active Treatment |
|---|---|
| Age, Continuous | 9.1 years STANDARD_DEVIATION 1.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 193 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 111 Participants |
| Race (NIH/OMB) More than one race | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 113 Participants |
| Sex: Female, Male Female | 145 Participants |
| Sex: Female, Male Male | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 238 |
| other Total, other adverse events | 143 / 238 |
| serious Total, serious adverse events | 3 / 238 |
Outcome results
Primary
Subjects With Treatment-Emergent Adverse Events (TEAEs)
TEAEs will be assessed starting following the first dose of study drug, and ending with the Follow-Up Visit or Early Termination Visit.
Time frame: Up to 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment-Phase Safety Population | Subjects With Treatment-Emergent Adverse Events (TEAEs) | Subjects with an AE leading to death | 0 Participants |
| Treatment-Phase Safety Population | Subjects With Treatment-Emergent Adverse Events (TEAEs) | Subjects with at least 1 TEAE | 143 Participants |
| Treatment-Phase Safety Population | Subjects With Treatment-Emergent Adverse Events (TEAEs) | Subjects with a related TEAE | 108 Participants |
| Treatment-Phase Safety Population | Subjects With Treatment-Emergent Adverse Events (TEAEs) | Subjects with a TEAE leading to discontinuation of study drug | 6 Participants |
| Treatment-Phase Safety Population | Subjects With Treatment-Emergent Adverse Events (TEAEs) | Subjects with an SAE | 2 Participants |
Secondary
Change From Baseline in ADHD-RS-5 Total Score
The clinician-administered ADHD-RS-5 is an 18-item scale that rates ADHD symptoms on a 4-point scale. Each item is scored using a combination of severity and frequency ratings from a range of 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting severe symptoms or a frequency of very often), so that the total ADHD-RS-5 scores range from 0 to 54. The 18 items can be divided into two 9-item subscales: One for hyperactivity/impulsivity and the other for inattentiveness.
Time frame: Up to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment-Phase Safety Population | Change From Baseline in ADHD-RS-5 Total Score | -29.0 score on a scale | Standard Deviation 11.21 |
Secondary
Change From Baseline in CGI-S
The CGI-S is a clinician-rated scale that evaluates the severity of psychopathology (ADHD symptoms in this study) on a scale from 1 (not at all ill) to 7 (among the most severely ill).
Time frame: Up to 12 months
Population: The Overall Efficacy Population was comprised of 225 subjects. Due to early terminations, 223 subjects remained at Visit 6 (Day 30) and 153 subjects remained at Visit 17 (Day 360)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Baseline (Visit 2 for new subjects and Visit 5 for roll-over subjects) | 1 = Normal, not at all | 0 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Baseline (Visit 2 for new subjects and Visit 5 for roll-over subjects) | 2 = Borderline mentally ill | 0 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Baseline (Visit 2 for new subjects and Visit 5 for roll-over subjects) | 3 = Mildly ill | 5 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Baseline (Visit 2 for new subjects and Visit 5 for roll-over subjects) | 4 = Moderately ill | 82 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Baseline (Visit 2 for new subjects and Visit 5 for roll-over subjects) | 5 = Markedly ill | 112 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Baseline (Visit 2 for new subjects and Visit 5 for roll-over subjects) | 6 = Severely ill | 26 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Baseline (Visit 2 for new subjects and Visit 5 for roll-over subjects) | 7 = Among the most extremely ill patients | 0 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Visit 17 (Day 360) | 1 = Normal, not at all | 47 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Visit 17 (Day 360) | 2 = Borderline mentally ill | 45 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Visit 17 (Day 360) | 3 = Mildly ill | 52 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Visit 17 (Day 360) | 4 = Moderately ill | 7 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Visit 17 (Day 360) | 5 = Markedly ill | 1 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Visit 17 (Day 360) | 6 = Severely ill | 1 Participants |
| Treatment-Phase Safety Population | Change From Baseline in CGI-S | Visit 17 (Day 360) | 7 = Among the most extremely ill patients | 0 Participants |
Secondary
Change From Baseline in Children's Sleep Habits Questionnaire
The modified, abbreviated Children's Sleep Habits Questionnaire (CSHQ) will be used to assess the sleep behavior. The CSHQ is a retrospective, 33-item parent questionnaire to examine sleep behavior in small children. Items are rated on a 3-point scale of Usually, Sometimes and Rarely for occurrences in a number of key sleep domains: bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Scores range from 33-99, with higher scores represent more disturbed sleep. Scores were obtained during a clinician-directed interview with the parent/guardian/caregiver.
Time frame: Up to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment-Phase Safety Population | Change From Baseline in Children's Sleep Habits Questionnaire | -4.3 score on a scale | Standard Deviation 5.2 |