Attention Deficit Disorder With Hyperactivity
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel-group study of NFC-1 versus placebo in adolescents with ADHD who have genetic disorders impacting mGluRs.
Detailed description
This is a randomized, double-blind, placebo-controlled, parallel-group study of adolescents with ADHD who have genetic disorders impacting mGluRs. Approximately 90 subjects will receive randomized treatment with NFC-1 or placebo. Dosing will be optimized during the first 4 weeks of treatment, based on clinical response and tolerability, and maintained for an additional 2 weeks.
Interventions
DRUGNFC-1
NFC-1 is supplied as size 2 hard gelatin capsules.
DRUGPlacebo
Matching placebo capsules
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
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subject has ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and Version 5 of the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-5) ≥ 28 at Baseline with or without conventional ADHD therapy. * Subject has an intelligence quotient (IQ) \> 79, based on the Wechsler Abbreviated Scale of Intelligence, second edition (WASI-II). * Subject has been genotyped previously and determined to have disruptive mutations in genes within the glutamate receptor metabotropic (GRM)-network as determined by the presence of copy number variations (CNVs) (GRM biomarker-positive subjects). The confirmation of a subject's positive status will be provided by the sponsor. * Subject is judged to be in general good health, other than having ADHD, based on medical history, physical examination, vital signs measurements, laboratory safety tests, and the Columbia Suicide Severity Rating Scale (C-SSRS) performed at the Screening Visit and/or prior to administration of investigational product (IP). * Subject has no clinically significant abnormality on electrocardiogram (ECG) performed at the Screening Visit and/or prior to administration of IP such as serious arrhythmia, bradycardia, tachycardia, cardiac conduction problems, or other abnormalities deemed to be a potential safety issue. * Parent/legal guardian and subject understand the study procedures and agree to the subject's participation in the study as indicated by parental/legal guardian signature on the subject informed consent form and subject signature on the assent form.
Exclusion criteria
* Subjects with prior diagnosis of comorbid major psychiatric disorders (ie, aside from ADHD), including major depression, bipolar disease, schizophrenia, pervasive development disorder, and intellectual disability. * Subject is currently taking a prohibited medication and/or is unwilling to wean off current ADHD medication to participate in the study * Subject has a history of any illness that in the opinion of the study investigator might confound the results of the study or poses an additional risk to the subject by his or her participation in the study. * Subject has a known history or presence of syncope, cardiac conduction problems (eg, clinically significant heart block), exercise-related cardiac events including syncope and pre-syncope, or clinically significant bradycardia. * Subject has a history of stroke, chronic seizures, or major neurological disorder which, in the opinion of the investigator, would interfere with the subject's ability to participate and/or be evaluated in the study.
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. |
| Clinical Global Impression - Global Improvement (CGI -I) Response | Visit 3 to 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 |
|---|---|
| NFC-1 Doses of NFC-1 will be administered as 100, 200, or 400 mg twice daily as capsules (size 2 hard gelatin capsules). | 47 |
| Placebo Matching placebo capsules | 50 |
| Total | 97 |
Baseline characteristics
| Characteristic | NFC-1 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 13.8 years STANDARD_DEVIATION 1.4 | 14.1 years STANDARD_DEVIATION 1.58 | 14.4 years STANDARD_DEVIATION 1.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 29 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 9 Participants | 3 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 | 29 Participants | 55 Participants | 26 Participants |
| Region of Enrollment United States | 47 Participants | 97 Participants | 50 Participants |
| Sex: Female, Male Female | 21 Participants | 36 Participants | 15 Participants |
| Sex: Female, Male Male | 26 Participants | 61 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 50 |
| other Total, other adverse events | 33 / 47 | 28 / 50 |
| serious Total, serious adverse events | 0 / 47 | 0 / 50 |
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: Modified Intent to Treat Population = all randomized subjects who took at least one dose of randomized study drug and have a valid baseline assessment and at least 1 valid post baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NFC-1 | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score | -14.2 units on a scale | Standard Error 1.82 |
| Placebo | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale, Version 5 (ADHD-RS-5) Total Score | -12.1 units on a scale | Standard Error 1.75 |
Primary
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 3 to Visit 8 (Week 6)
Population: Modified Intent to Treat Population = all randomized subjects who took at least one dose of randomized study drug and have a valid baseline assessment and at least 1 valid post baseline assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NFC-1 | Clinical Global Impression - Global Improvement (CGI -I) Response | 26 Participants |
| Placebo | Clinical Global Impression - Global Improvement (CGI -I) Response | 16 Participants |