ADHD
Conditions
Brief summary
The study is a multicenter, dose-optimized, double-blind, randomized, placebo-controlled, parallel efficacy laboratory classroom study with KP415 in children with Attention-Deficit/Hyperactivity Disorder (ADHD).
Detailed description
The study will consist of a Screening Period, an Open-Label Dose Optimization Phase, a Double-Blind Treatment Phase and a Follow-Up Visit, as follows: * Screening Period: Subjects will undergo a screening period up to 49 days prior to entering into the Open-Label Dose Optimization Phase. * Open-Label 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. * Double-Blind Treatment Phase: Eligible subjects will be randomized to receive single daily doses of KP415 or Placebo for 7 days according to a randomization schedule. The dose of KP415 given in the Treatment Phase will be the same as the optimized dose of KP415 at the end of the Dose Optimization Phase. All subjects will receive their assigned treatment daily for 7 days. The dose will be the same at each day of the Treatment Period. Efficacy and safety assessments will be performed after the last dose of the Treatment Period. * 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
Daily dose
DRUGPlacebo oral capsule
Daily dose
Sponsors
Zevra Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
3-week, open-label dose-optimization phase followed by a 1-week randomized, double-blind treatment phase
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. 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 any history of attempted suicide or clinically significant suicidal ideation or subject has a C-SSRS score for suicidal ideation ≥2. 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 |
|---|---|---|
| Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores | Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase | The SKAMP scale is a validated rating of subjective impairment of classroom behaviors in children with ADHD. It comprises 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment) by trained study personnel (Swanson 1998). The SKAMP-C score was obtained by summing the rating values for each of the 13 items (range: 0-78), with higher scores indicating greater impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A) | Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase | The PERMP is an adjusted math test designed to assess attention in children with ADHD (Swanson 1999). The test measures attention through a subject's ability to initiate, self-monitor, and complete the math test. A Placement PERMP was performed early in the trial to assure that subjects could complete at least the basic level of math problems and to determine the appropriate level of math to be assigned during the remainder of the study. The PERMP is an individually calibrated 5-page mathematics worksheet consisting of 400 problems. PERMP-A scores document the number of problems attempted, from 0 to 400, and thus higher scores represent a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment KP415 oral capsule 20, 30 or 40 mg
KP415 oral capsule: Daily dose | 74 |
| Placebo Treatment Placebo oral capsule
Placebo oral capsule: Daily dose | 76 |
| Total | 150 |
Baseline characteristics
| Characteristic | Active Treatment | Total | Placebo Treatment |
|---|---|---|---|
| Age, Continuous | 9.6 years STANDARD_DEVIATION 1.6 | 9.6 years STANDARD_DEVIATION 1.6 | 9.6 years STANDARD_DEVIATION 1.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 40 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 110 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 56 Participants | 31 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 10 Participants | 4 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 38 Participants | 76 Participants | 38 Participants |
| Region of Enrollment United States | 74 participants | 150 participants | 76 participants |
| Sex: Female, Male Female | 30 Participants | 58 Participants | 28 Participants |
| Sex: Female, Male Male | 44 Participants | 92 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 155 | 0 / 74 | 0 / 76 |
| other Total, other adverse events | 104 / 155 | 13 / 74 | 6 / 76 |
| serious Total, serious adverse events | 0 / 155 | 0 / 74 | 0 / 76 |
Outcome results
Primary
Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores
The SKAMP scale is a validated rating of subjective impairment of classroom behaviors in children with ADHD. It comprises 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment) by trained study personnel (Swanson 1998). The SKAMP-C score was obtained by summing the rating values for each of the 13 items (range: 0-78), with higher scores indicating greater impairment.
Time frame: Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores | -4.87 score on a scale | Standard Error 0.62 |
| Placebo Treatment | Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores | 0.536 score on a scale | Standard Error 0.7 |
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A)
The PERMP is an adjusted math test designed to assess attention in children with ADHD (Swanson 1999). The test measures attention through a subject's ability to initiate, self-monitor, and complete the math test. A Placement PERMP was performed early in the trial to assure that subjects could complete at least the basic level of math problems and to determine the appropriate level of math to be assigned during the remainder of the study. The PERMP is an individually calibrated 5-page mathematics worksheet consisting of 400 problems. PERMP-A scores document the number of problems attempted, from 0 to 400, and thus higher scores represent a better outcome.
Time frame: Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A) | 25.82 score on a scale | Standard Error 3.44 |
| Placebo Treatment | Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A) | 2.25 score on a scale | Standard Error 3.05 |