Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD

Open-Label Treatment Trial to Assess the Short-Term Tolerability, Safety, and Efficacy of Methylphenidate Hydrochloride Extended-Release Liquid Formulation in High-Functioning Autism Spectrum Disorder Adults With Attention-Deficit/Hyperactivity Disorder

The purpose of this study is to determine whether methylphenidate hydrochloride extended release liquid formulation is safe and effective in the treatment of attention-deficit/hyperactivity disorder (ADHD) in high-functioning adults with autism spectrum disorders (ASD).

Inclusion Criteria

• Male or female participants between 18 and 40 years of age (inclusive)
• Fulfills DSM-5 diagnostic criteria for autism spectrum disorder as established by the clinical diagnostic interview and ADOS
• Fulfills DSM-5 diagnostic criteria for ADHD as established by the clinical diagnostic interview and confirmed by the K-SADS-E ADHD module
• Participants with at least moderately severe symptoms of ASD as demonstrated by SRS raw score ≥ 85 and CGI-ASD severity score ≥ 4
• Participants with at least moderately severe symptoms of ADHD as assessed by AISRS score ≥ 24 and CGI-ADHD severity score ≥ 4
• Participants and/or their legal representative must understand the nature of the study. Participants and/or their legal representative must sign an IRB-approved informed consent form before initiation of any study procedures.
• Participants and/or their legal representative must have a level of understanding sufficient to communicate with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol.
• Participant must be able to participate in mandatory blood draws.
• Participant with major mood and/or anxiety disorders will be allowed to participate in the study provided they do not meet any exclusionary criteria.

Exclusion Criteria

• Impaired intellectual capacity (IQ <85)
• Participant is unable to communicate due to delay in, or total lack of, spoken language development (grossly impaired language skills)
• Clinically unstable psychiatric conditions or judged to be at serious safety risk to self (suicidal risk) or others (within past 30 days).
• Subjects currently (within past 30 days) experiencing significant features of anxiety, mood, or psychotic disorder as indicated by a >3 score on the disorder-specific Clinical Global Impression-Severity (CGI-S) clinician-rated scale.
• History of substance use (except nicotine or caffeine) within past 3 months (inclusive) or with urine drug screen positive for substances of abuse
• Subjects with a medical condition or treatment that will either jeopardize subject safety or affect the scientific merit of the study, including:
• Pregnant or nursing females or females with a positive beta-HCG pregnancy test.
• Uncorrected hypothyroidism or hyperthyroidism.
• History of non-febrile seizures within last 1 month without a clear and resolved etiology.
• History of renal or hepatic impairment.
• Glaucoma
• Tourette's syndrome and/or motor tics
• Serious, unstable systemic illness
• Personal history of cardiac disease or a family history of non-geriatric cardiac disease or death
• Clinically significant abnormal baseline laboratory values which include the following:
• Values more than 20% above the upper range of the laboratory standard for a basic metabolic screen.
• Systolic and diastolic blood pressure parameters above 140 and 90, respectively.
• Resting heart rate outside of 60-100 bpm.
• Abnormal ECG parameters defined as QTC> 460msec, QRS>120 msec, and/or PR>200 msec.
• ECG evidence of ischemia or arrhythmia as reviewed by an independent cardiologist.
• Participant with a history of non-response to adequate trial of methylphenidate (therapeutic dose for an adequate duration) as determined by clinician.
• History of intolerance or an allergic reaction to methylphenidate.
• Current or recent treatment (within the past 30 days) with current stimulant class of anti-ADHD medications.
• Current treatment with monoamine oxidase inhibitors (MAOIs)
• Current treatment with a first- or second-generation antipsychotic medication on a dose that has not been stable for at least 4 weeks prior to baseline visit.
• Current treatment with a psychotropic medication on a dose that has not been stable for at least 4 weeks prior to baseline visit.
• Investigator and his/her immediate family, defined as the investigator's spouse, parent, child, grandparent, or grandchild.

While stably treated or remitted hypertension is not exclusionary, any subject with a history of high blood pressure will be asked to obtain approval from their primary care physician certifying that their hypertension is stable and that they may safely begin stimulant therapy. Subjects will be informed of the cardiovascular risks of MPH, and any subject with a history of hypertension who is unwilling to consult with their current treater-or to grant study staff permission to consult with the subject's current treater-will be excluded because of the potential risks to subject safety. Per the FDA approved MPH-ERLF package insert, high blood pressure is not a contraindication of MPH therapy; however, due to the cardiovascular side effects, it is recommended that subjects with a history of high blood pressure be monitored carefully. Cardiovascular risk factors are carefully monitored throughout the study for all subjects by way of screening electrocardiograms and pulse/blood pressure readings at every office visit. Patients with current untreated hypertension are not eligible.