Attention Deficit Hyperactivity Disorder
Conditions
Brief summary
This is PART A of a 2-part, 6-week, double-blind, dose-optimization, parallel-group study in children and adolescents (ages 6-17 years) with ADHD with and without CNVs in specific genes implicated in glutamatergic signaling and neuronal activity. Parts A will include subjects determined to have a specific gene mutations implicated in glutamatergic signaling and neuronal connectivity.
Interventions
DRUGAEVI-001
Oral doses of 100 mg, 200 mg or 400 mg of AEVI-001 will be administered twice daily during the treatment period.
DRUGPlacebo
Oral doses of 100 mg, 200 mg or 400 mg of Placebo will be administered twice daily during the treatment period.
Sponsors
Aevi Genomic Medicine, LLC, a Cerecor company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Subject and parent/legally authorized representative (LAR) can speak English fluently and have provided written informed consent, and assent (as applicable) for this study. 2. Subject is 6 to 17 years of age (inclusive) at the time of consent/assent. The date of signature of the informed consent/assent is defined as the beginning of the Screening Period. This inclusion criterion will only be assessed at the Screening Visit (Visit 1). 3. Subject is male or non-pregnant, non-lactating female, who if of childbearing potential agrees to comply with any applicable contraceptive requirements prior to administration of investigational product (IP). 4. Subject meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD based upon DSM 5 criteria. 5. Subject has a minimum score of ≥28 on the ADHD-RS-5 at the Baseline Visit (Visit 2). 6. Subject has been genotyped previously and has their identity confirmed (if required).
Exclusion criteria
1. Subject or parent/LAR is, in the opinion of the investigator, mentally or legally incapacitated, has significant emotional problems at the time of the Screening Visit (Visit 1) which could interfere with the conduct of study evaluations. 2. Subject has a current, controlled or uncontrolled, co-morbid major psychiatric diagnosis (aside from ADHD), including an anxiety disorder, major depression, bipolar disease, schizophrenia (or any psychotic disorder), and moderate or severe intellectual disability. Mild anxiety and/or depressive symptoms that do not meet diagnostic criteria for an anxiety disorder or major depression and/or do not require treatment are not exclusionary. 3. Subject has autism spectrum disorder to include a DSM-IV diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder. 4. Subject is currently taking any medication that might confound the results of safety assessments conducted in the study. 5. Subject has a known history of cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, or other serious cardiac problems. 6. Subject has any clinically significant abnormality on 12-lead ECG performed at the Screening Visit (Visit 1) and/or the Baseline Visit (Visit 2) such as serious arrhythmia, cardiac conduction problems, or other abnormalities deemed to be a potential safety issue.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score | Baseline to Visit 8 (Week 6) | The ADHD-RS-5 is comprised of 18 frequency items and 12 impairment items. Each frequency item was scored on a scale from 0 = Never or rarely to 3 = Very often. The ADHD-RS-5 total score was calculated as the sum of the 18 frequency item scores. The total score ranges from 0 to 54. Higher scores indicate greater symptom severity. Change from baseline value were calculated as the assessment value minus the baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Global Improvement (CGI -I) Response | Visit 8 (Week 6) | The CGI-I item is rated on a 7-point scale from 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. Response is defined as achieving a CGI-I score of 1 or 2, scores of 3 to 7 or missing are defined as Non Response |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AEVI-001 100 mg, 200 mg or 400 mg of AEVI-001 b.i.d. | 34 |
| Placebo Placebo b.i.d. | 35 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lack of Compliance | 1 | 0 |
| Overall Study | Lack of Efficacy | 3 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | AEVI-001 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 9.9 years STANDARD_DEVIATION 2.95 | 10.8 years STANDARD_DEVIATION 2.86 | 10.4 years STANDARD_DEVIATION 2.92 |
| Age, Customized 13 to 17 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Customized 6 to 12 years | 26 Participants | 27 Participants | 53 Participants |
| Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score | 39.0 units on a scale STANDARD_DEVIATION 6.76 | 38.1 units on a scale STANDARD_DEVIATION 8.29 | 38.6 units on a scale STANDARD_DEVIATION 7.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 31 Participants | 59 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 | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 20 Participants | 44 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 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 | 7 Participants | 12 Participants | 19 Participants |
| Region of Enrollment United States | 34 participants | 35 participants | 69 participants |
| Sex: Female, Male Female | 7 Participants | 14 Participants | 21 Participants |
| Sex: Female, Male Male | 27 Participants | 21 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 35 |
| other Total, other adverse events | 12 / 34 | 11 / 35 |
| serious Total, serious adverse events | 1 / 34 | 0 / 35 |
Outcome results
Primary
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score
The ADHD-RS-5 is comprised of 18 frequency items and 12 impairment items. Each frequency item was scored on a scale from 0 = Never or rarely to 3 = Very often. The ADHD-RS-5 total score was calculated as the sum of the 18 frequency item scores. The total score ranges from 0 to 54. Higher scores indicate greater symptom severity. Change from baseline value were calculated as the assessment value minus the baseline value.
Time frame: Baseline to Visit 8 (Week 6)
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AEVI-001 | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score | -9.17 units on a scale | Standard Error 2.235 |
| Placebo | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score | -11.34 units on a scale | Standard Error 2.122 |
Secondary
Clinical Global Impression - Global Improvement (CGI -I) Response
The CGI-I item is rated on a 7-point scale from 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. Response is defined as achieving a CGI-I score of 1 or 2, scores of 3 to 7 or missing are defined as Non Response
Time frame: Visit 8 (Week 6)
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AEVI-001 | Clinical Global Impression - Global Improvement (CGI -I) Response | 9 Participants |
| Placebo | Clinical Global Impression - Global Improvement (CGI -I) Response | 11 Participants |