ADHD, Autism
Conditions
Keywords
Quillivant
Brief summary
The purpose of this study is to determine whether Quillivant XR is effective in the treatment of ADHD in children with Autism Spectrum Disorder (ASD).
Detailed description
To evaluate the safety and tolerability of low to moderate dose effects of Quillivant XR (liquid methylphenidate) and to observe changes in ADHD symptoms and functional outcomes in children with ASD and ADHD. The investigators propose to investigate the low to moderate dose range of methylphenidate compared with a very low dose with a gradual dose escalation schedule because children with ASD have been found to be more sensitive to the adverse effects of methylphenidate (especially in medium to high doses) than children without ASD.
Interventions
DRUGVery Low Dose Quillivant XR
Oral suspension dose once a day increasing to a 10mg dose
DRUGLow Dose Quillivant XR
Oral suspension dose once a day increasing to a 20mg dose
DRUGModerate Dose Quillivant XR
Oral suspension dose once a day increasing to a 40mg dose
Sponsors
Pfizer
Seattle Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* A clinical diagnosis of Autistic disorder or Asperger's disorder by DSM-IV or Autism Spectrum Disorder by DSM-V. * A DSM-V diagnosis of ADHD based upon the K-SADS-P. * Clinical Global Impressions - Severity for ADHD (CGI-S-ADHD) rating \> 4. * Findings on physical exam, labs and ECG are judged to be normal for age with pulse and blood pressure within 95% of age and gender mean. * Informed consent by a parent or legal guardian, and assent for children with developmental age 7 years or older. * At least one parent fluent in English
Exclusion criteria
* History of Seizure disorder (Febrile seizures are non-exclusionary). * History of Intellectual Disability (IQ\< 70) * Treatment with MAO Inhibitor (or within 14 days following discontinuation of MAO Inhibitor). * Other psychotropic medication other than stable dose of Selective Serotonin Reuptake Inhibitors, which is permitted) * Known to be hypersensitive to methylphenidate, or other components of Quillivant XR * Cardiac or other medical contraindications for stimulant trial (e.g., family history of heart attack at age younger than 40 years, personal history of heart disease, history of fainting while exercising, structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. If any doubt, children will be referred to a cardiologist for a cardiac clearance. * Raynaud's disease * Pregnancy or Breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ADHD Rating Scale - IV | once a week for 6 weeks | Measures the severity of Total ADHD symptoms, Inattention and Hyperactivity/Impulsive symptoms. The Inattention and Hyperactivity/Impulsive symptoms can range from 0 to 27 each, with a higher score reflecting more severe ADHD symptoms. The total score is calculated by summing the inattention and Hyperactivity/Impulsive subscales. The total score can range from 0 to 54 with a higher score reflecting more severe ADHD symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impressions-ADHD - Severity | once a week for 6 weeks | The CGI-S scale summarizes the clinician's impression of the participant's symptom severity and ranges from 1-7 with 1 representing normal (not at all ill) and 7 representing extremely ill. |
| Clinical Global Impression - Improvement (CGI-I) | once a week for 6 weeks | The CGI-I scale summarizes the clinician's impression of the participant's symptom improvement and ranges from 1-7 with 1 representing very much improved and 7 representing very much worse. |
Countries
United States
Participant flow
Recruitment details
Eligible participants were recruited from the investigators' practices, clinic referrals, and letter mailings. Participants were enrolled between September 2014 and September 2016.
Pre-assignment details
Of the 36 participants enrolled, 27 were randomized to receive treatment. 3 participants withdrew, 2 due to time commitment issues and 1 due to stress over screening. 6 participants were deemed ineligible for the study due to no Autism Spectrum Disorder (ASD) diagnosis based on screening assessments.
Participants by arm
| Arm | Count |
|---|---|
| Very Low Dose Quillivant XR Patients in this treatment arm are given Quillivant XR (a liquid medication) to treat ADHD at a very low dose level for 6 weeks.
Very Low Dose Quillivant XR: Oral suspension dose once a day starting at 5mg and increasing to a 10mg dose | 9 |
| Low Dose Quillivant XR Patients in this treatment arm are given Quillivant XR (a liquid medication) to treat ADHD at a low dose level for 6 weeks.
Low Dose Quillivant XR: Oral suspension dose once a day starting at 5mg and increasing to a 20mg dose | 9 |
| Moderate Dose Quillivant XR Patients in this treatment arm are given Quillivant XR (a liquid medication) to treat ADHD at a moderate dose level for 6 weeks.
Moderate Dose Quillivant XR: Oral suspension dose once a day starting at 5mg and increasing to a 40mg dose | 9 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Low Dose Quillivant XR | Moderate Dose Quillivant XR | Very Low Dose Quillivant XR | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 9 Participants | 9 Participants | 27 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.00 years STANDARD_DEVIATION 2.96 | 10.22 years STANDARD_DEVIATION 3.03 | 9.33 years STANDARD_DEVIATION 2.92 | 9.19 years STANDARD_DEVIATION 3 |
| Region of Enrollment United States | 9 participants | 9 participants | 9 participants | 26 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 8 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 9 | 8 / 9 | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
ADHD Rating Scale - IV
Measures the severity of Total ADHD symptoms, Inattention and Hyperactivity/Impulsive symptoms. The Inattention and Hyperactivity/Impulsive symptoms can range from 0 to 27 each, with a higher score reflecting more severe ADHD symptoms. The total score is calculated by summing the inattention and Hyperactivity/Impulsive subscales. The total score can range from 0 to 54 with a higher score reflecting more severe ADHD symptoms.
Time frame: once a week for 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Total Score | 30.33 units on a scale | Standard Deviation 9.27 |
| Very Low Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Inattention Subscale Score | 17.89 units on a scale | Standard Deviation 3.95 |
| Very Low Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 12.44 units on a scale | Standard Deviation 7.91 |
| Very Low Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Inattention Subscale Score | 16.78 units on a scale | Standard Deviation 4.18 |
| Very Low Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 10.56 units on a scale | Standard Deviation 8.16 |
| Very Low Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Total Score | 27.33 units on a scale | Standard Deviation 11.14 |
| Very Low Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 11.56 units on a scale | Standard Deviation 6.25 |
| Very Low Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Inattention Subscale Score | 16.67 units on a scale | Standard Deviation 2.74 |
| Very Low Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Total Score | 28.22 units on a scale | Standard Deviation 7.24 |
| Very Low Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Total Score | 26.67 units on a scale | Standard Deviation 10.2 |
| Very Low Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Inattention Subscale Score | 14.33 units on a scale | Standard Deviation 6.26 |
| Very Low Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 12.33 units on a scale | Standard Deviation 5.7 |
| Very Low Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 9.22 units on a scale | Standard Deviation 7.55 |
| Very Low Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Inattention Subscale Score | 14.56 units on a scale | Standard Deviation 5.53 |
| Very Low Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Total Score | 23.78 units on a scale | Standard Deviation 11.51 |
| Very Low Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Total Score | 21.67 units on a scale | Standard Deviation 7.78 |
| Very Low Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Inattention Subscale Score | 12.89 units on a scale | Standard Deviation 5.01 |
| Very Low Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 8.78 units on a scale | Standard Deviation 5.67 |
| Low Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Total Score | 31.67 units on a scale | Standard Deviation 14.67 |
| Low Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Inattention Subscale Score | 16.33 units on a scale | Standard Deviation 6.89 |
| Low Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 15.33 units on a scale | Standard Deviation 8.23 |
| Low Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Inattention Subscale Score | 14.00 units on a scale | Standard Deviation 5.83 |
| Low Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 14.33 units on a scale | Standard Deviation 7.38 |
| Low Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Total Score | 28.33 units on a scale | Standard Deviation 12.41 |
| Low Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 10.22 units on a scale | Standard Deviation 5.24 |
| Low Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Total Score | 22.22 units on a scale | Standard Deviation 9.9 |
| Low Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Inattention Subscale Score | 12.00 units on a scale | Standard Deviation 5.22 |
| Low Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 6.88 units on a scale | Standard Deviation 4.42 |
| Low Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Inattention Subscale Score | 8.38 units on a scale | Standard Deviation 5.9 |
| Low Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Total Score | 15.25 units on a scale | Standard Deviation 9.77 |
| Low Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 9.38 units on a scale | Standard Deviation 4.75 |
| Low Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Total Score | 18.88 units on a scale | Standard Deviation 9.06 |
| Low Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Inattention Subscale Score | 9.50 units on a scale | Standard Deviation 4.57 |
| Low Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 6.56 units on a scale | Standard Deviation 4.28 |
| Low Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Total Score | 16.11 units on a scale | Standard Deviation 8.99 |
| Low Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Inattention Subscale Score | 9.56 units on a scale | Standard Deviation 6.17 |
| Moderate Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Inattention Subscale Score | 18.11 units on a scale | Standard Deviation 4.43 |
| Moderate Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 12.78 units on a scale | Standard Deviation 3.87 |
| Moderate Dose Quillivant XR - Week 1 | ADHD Rating Scale - IV | Total Score | 30.89 units on a scale | Standard Deviation 6.17 |
| Moderate Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Inattention Subscale Score | 14.67 units on a scale | Standard Deviation 5.15 |
| Moderate Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Total Score | 26.00 units on a scale | Standard Deviation 5.87 |
| Moderate Dose Quillivant XR - Week 2 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 11.33 units on a scale | Standard Deviation 2.78 |
| Moderate Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 11.78 units on a scale | Standard Deviation 6.26 |
| Moderate Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Inattention Subscale Score | 13.67 units on a scale | Standard Deviation 6.98 |
| Moderate Dose Quillivant XR - Week 3 | ADHD Rating Scale - IV | Total Score | 25.44 units on a scale | Standard Deviation 12.7 |
| Moderate Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Inattention Subscale Score | 13.56 units on a scale | Standard Deviation 5.1 |
| Moderate Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 9.67 units on a scale | Standard Deviation 5.87 |
| Moderate Dose Quillivant XR - Week 4 | ADHD Rating Scale - IV | Total Score | 23.22 units on a scale | Standard Deviation 10.02 |
| Moderate Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 9.22 units on a scale | Standard Deviation 5.83 |
| Moderate Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Total Score | 22.22 units on a scale | Standard Deviation 10.03 |
| Moderate Dose Quillivant XR - Week 5 | ADHD Rating Scale - IV | Inattention Subscale Score | 13.00 units on a scale | Standard Deviation 5.55 |
| Moderate Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Hyperactivity Subscale Score | 7.33 units on a scale | Standard Deviation 2.87 |
| Moderate Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Inattention Subscale Score | 11.78 units on a scale | Standard Deviation 5.43 |
| Moderate Dose Quillivant XR - Week 6 | ADHD Rating Scale - IV | Total Score | 19.11 units on a scale | Standard Deviation 7.44 |
Secondary
Clinical Global Impression - Improvement (CGI-I)
The CGI-I scale summarizes the clinician's impression of the participant's symptom improvement and ranges from 1-7 with 1 representing very much improved and 7 representing very much worse.
Time frame: once a week for 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Very Low Dose Quillivant XR - Week 1 | Clinical Global Impression - Improvement (CGI-I) | 3.89 units on a scale | Standard Deviation 0.6 |
| Very Low Dose Quillivant XR - Week 2 | Clinical Global Impression - Improvement (CGI-I) | 3.56 units on a scale | Standard Deviation 0.88 |
| Very Low Dose Quillivant XR - Week 3 | Clinical Global Impression - Improvement (CGI-I) | 3.44 units on a scale | Standard Deviation 0.53 |
| Very Low Dose Quillivant XR - Week 4 | Clinical Global Impression - Improvement (CGI-I) | 3.22 units on a scale | Standard Deviation 0.83 |
| Very Low Dose Quillivant XR - Week 5 | Clinical Global Impression - Improvement (CGI-I) | 3.00 units on a scale | Standard Deviation 1 |
| Very Low Dose Quillivant XR - Week 6 | Clinical Global Impression - Improvement (CGI-I) | 2.89 units on a scale | Standard Deviation 0.78 |
| Low Dose Quillivant XR - Week 1 | Clinical Global Impression - Improvement (CGI-I) | 3.78 units on a scale | Standard Deviation 1.3 |
| Low Dose Quillivant XR - Week 2 | Clinical Global Impression - Improvement (CGI-I) | 3.00 units on a scale | Standard Deviation 0.87 |
| Low Dose Quillivant XR - Week 3 | Clinical Global Impression - Improvement (CGI-I) | 2.22 units on a scale | Standard Deviation 0.83 |
| Low Dose Quillivant XR - Week 4 | Clinical Global Impression - Improvement (CGI-I) | 1.63 units on a scale | Standard Deviation 0.74 |
| Low Dose Quillivant XR - Week 5 | Clinical Global Impression - Improvement (CGI-I) | 2.13 units on a scale | Standard Deviation 0.99 |
| Low Dose Quillivant XR - Week 6 | Clinical Global Impression - Improvement (CGI-I) | 2.00 units on a scale | Standard Deviation 0.87 |
| Moderate Dose Quillivant XR - Week 1 | Clinical Global Impression - Improvement (CGI-I) | 3.33 units on a scale | Standard Deviation 0.5 |
| Moderate Dose Quillivant XR - Week 2 | Clinical Global Impression - Improvement (CGI-I) | 3.11 units on a scale | Standard Deviation 0.6 |
| Moderate Dose Quillivant XR - Week 3 | Clinical Global Impression - Improvement (CGI-I) | 2.67 units on a scale | Standard Deviation 1.12 |
| Moderate Dose Quillivant XR - Week 4 | Clinical Global Impression - Improvement (CGI-I) | 2.89 units on a scale | Standard Deviation 0.6 |
| Moderate Dose Quillivant XR - Week 5 | Clinical Global Impression - Improvement (CGI-I) | 2.56 units on a scale | Standard Deviation 1.01 |
| Moderate Dose Quillivant XR - Week 6 | Clinical Global Impression - Improvement (CGI-I) | 2.22 units on a scale | Standard Deviation 0.83 |
Secondary
Clinical Global Impressions-ADHD - Severity
The CGI-S scale summarizes the clinician's impression of the participant's symptom severity and ranges from 1-7 with 1 representing normal (not at all ill) and 7 representing extremely ill.
Time frame: once a week for 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Very Low Dose Quillivant XR - Week 1 | Clinical Global Impressions-ADHD - Severity | 4.78 units on a scale | Standard Deviation 0.44 |
| Very Low Dose Quillivant XR - Week 2 | Clinical Global Impressions-ADHD - Severity | 4.33 units on a scale | Standard Deviation 0.87 |
| Very Low Dose Quillivant XR - Week 3 | Clinical Global Impressions-ADHD - Severity | 4.44 units on a scale | Standard Deviation 0.88 |
| Very Low Dose Quillivant XR - Week 4 | Clinical Global Impressions-ADHD - Severity | 4.33 units on a scale | Standard Deviation 0.87 |
| Very Low Dose Quillivant XR - Week 5 | Clinical Global Impressions-ADHD - Severity | 4.11 units on a scale | Standard Deviation 1.05 |
| Very Low Dose Quillivant XR - Week 6 | Clinical Global Impressions-ADHD - Severity | 4.00 units on a scale | Standard Deviation 0.87 |
| Low Dose Quillivant XR - Week 1 | Clinical Global Impressions-ADHD - Severity | 4.33 units on a scale | Standard Deviation 1.12 |
| Low Dose Quillivant XR - Week 2 | Clinical Global Impressions-ADHD - Severity | 4.00 units on a scale | Standard Deviation 1.22 |
| Low Dose Quillivant XR - Week 3 | Clinical Global Impressions-ADHD - Severity | 3.67 units on a scale | Standard Deviation 1 |
| Low Dose Quillivant XR - Week 4 | Clinical Global Impressions-ADHD - Severity | 2.75 units on a scale | Standard Deviation 1.16 |
| Low Dose Quillivant XR - Week 5 | Clinical Global Impressions-ADHD - Severity | 2.88 units on a scale | Standard Deviation 1.25 |
| Low Dose Quillivant XR - Week 6 | Clinical Global Impressions-ADHD - Severity | 2.78 units on a scale | Standard Deviation 1.3 |
| Moderate Dose Quillivant XR - Week 1 | Clinical Global Impressions-ADHD - Severity | 4.89 units on a scale | Standard Deviation 0.33 |
| Moderate Dose Quillivant XR - Week 2 | Clinical Global Impressions-ADHD - Severity | 4.56 units on a scale | Standard Deviation 0.53 |
| Moderate Dose Quillivant XR - Week 3 | Clinical Global Impressions-ADHD - Severity | 4.11 units on a scale | Standard Deviation 0.6 |
| Moderate Dose Quillivant XR - Week 4 | Clinical Global Impressions-ADHD - Severity | 4.00 units on a scale | Standard Deviation 0.71 |
| Moderate Dose Quillivant XR - Week 5 | Clinical Global Impressions-ADHD - Severity | 3.56 units on a scale | Standard Deviation 0.88 |
| Moderate Dose Quillivant XR - Week 6 | Clinical Global Impressions-ADHD - Severity | 3.44 units on a scale | Standard Deviation 1.24 |