Clinical trial NCT02096952
Conditions: Attention-deficit/Hyperactivity Disorder Autism Spectrum Disorder
Keywords: Attention-deficit/hyperactivity disorder ADHD Autism spectrum disorder ASD High-functioning ASD Asperger's disorder Asperger's
Sponsor: Massachusetts General Hospital
Start date: 2014-05-01; Completion date: 2018-01-01
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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).

Detailed description:

Arms: arm 1: Methylphenidate extended-release liquid formulation
Interventions: intervention 1: Methylphenidate extended-release liquid formulation
Intervention descriptions: intervention 1: None

Protocol documents:
Prot_SAP_000.pdf: 
Methylphenidate ER Liquid Formulation in Adults with ASD+ADHD 
Version: Amendment 41 RtR, submitted to the IRB 12/09/2016  
 
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Study Protocol:  
An 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 
 
Gagan Joshi, MD 
Massachusetts General Hospital 
Clinical and Research Program in Pediatric Psychopharmacology 
 
Version Date: Amendment 41 RtR, submitted to the IRB: 12/09/2016  
 
 


Methylphenidate ER Liquid Formulation in Adults with ASD+ADHD 
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1. BACKGROUND AND SIGNIFICANCE 
 
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by 
variable presentation of difficulties with socialization, reciprocal communication, and 
restrictive/repetitive behaviors (APA, 2013). An increasingly higher prevalence of ASD is 
documented in each successive epidemiological survey and the disorder is now 
estimated to affect up to 2% of youth in the general population (Blumberg et al., 2013). 
This rise in prevalence is in part attributed to improved recognition of autism in 
intellectually capable populations (ADDM Network, 2012). 
 
ADHD is the most common psychiatric disorder recognized in youth and adults with 
ASD and greatly add to their morbidity and dysfunction, particularly in those with intact 
intellectual capacity (Joshi et al., 2010, 2013; Stahlberg et al., 2004; Ryden & Bejerot et 
al., 2008; Ghaziuddin & Zafar 2008; Frazier et al., 2001; Wozniak et al., 1997; de Bruin 
et al. 2007; Sinzig et al., 2009). Youth and young adults with intact intellectual capacity 
constitute a majority of the psychiatrically referred ASD population (Joshi et al., 2010, 
2013, [under review]; Ryden & Bejerot, 2008; Frazier et al., 2001; Wozniak et al., 1997). 
Nearly two-thirds (ranging from 37-68%) of clinically referred populations of adults with 
ASD suffer from ADHD (Joshi et al., 2013; Stahlberg et al., 2004; Ryden & Bejerot et 
al., 2008). 
 
Our team of researchers has repeatedly documented striking homology in the 
phenotypic presentation of ADHD in youth irrespective of comorbidity with ASD, 
suggesting that the clinical presentation ADHD in ASD is typical of the disorder (Joshi et 
al., 2014 [under review]; Wozniak et al., 1997; Frazier et al., 2001). 
 
As ADHD is functionally more impairing in the context of intellectual demands, the 
presence of ADHD in intellectually capable individuals with ASD causes significant 
impairment in their intellectual as well as social functioning as they usually co-function 
alongside typically developing peers (Joshi et al., 2014, [under review]). ADHD-related 
impairment in intellectual and social functioning is particularly disabling to those 
transition-age HF-ASD individuals who attend college and are therefore especially 
vulnerable to social and transition-related challenges. 
 
While there is no established pharmacological treatment for the core features of ASD, 
there are well-established evidence-based pharmacotherapies available for the 
management of psychiatric disorders in typically developing individuals that frequently 
co-occur with ASD. Considering that ADHD is known to respond to a variety of 
pharmacological interventions in typically developing individuals, morbidity and 
impairments in autistic individuals can be minimized by identifying and offering 
treatments for ADHD comorbid with ASD. 
 
In general, the psychopharmacologic treatment response in ASD populations is 
atypically associated with higher susceptibility to adverse effects. Treatment literature 
suggests that compared to general population, individuals with ASD may be more 
susceptible to adverse responses to stimulant medications (Campbell et al., 1972 & 


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1976; Stigler et al., 2004), and this susceptibility could be dose-related (Handen et al., 
2000). 
 
In clinical practice, ASD youth are routinely treated with stimulants for symptoms of 
ADHD and surveys suggest a steady rise in this trend (Croen et al., 2006; Langworthy-
Lam et al., 2002). Of all psychotropic medications, the stimulant class - methylphenidate 
(MPH) in particular - is the most widely prescribed in this population (Langworthy-Lam 
et al., 2002; Aman et al, 1995). Although empirical evidence on the tolerability and 
efficacy of stimulants for managing ADHD in ASD populations is limited, MPH remains 
the most studied anti-ADHD medication in ASD populations (RUPP, 2005; Handen et 
al., 2000; DiMartino et al., 2004).  
 
ASD youth with ADHD respond to a lower-than-expected dose of MPH (0.3mg/kg/day; 
Handen et al., 2000) with the magnitude of response typically less than that observed in 
typicals (50% vs. 70-80%; RUPP, 2005 vs. MTA, 2001). In the largest controlled trial of 
stimulants in an ASD population to date (which included ASD youth with impaired 
intellectual capacity), half of the children were reported to have experienced moderate 
response to oral MPH in hyperactivity and/or impulsiveness with side effects that were, 
in some cases, severe enough to discontinue treatment (RUPP, 2005). In this trial, the 
less-than-expected MPH response could be due to: 1) the presence of intellectual 
disability (ID; IQ<70) as a negative confounder, 2) a judgment of MPH response based 
only on improvement in hyperactivity/impulsiveness (where the outcome of 
inattentiveness could not be evaluated due to subjects’ lack of verbal abilities), or 3) the 
assessment of hyperactivity and/or impulsivity with the Aberrant Behavior Checklist 
(ABC), a scale limited in capturing all of the dimensions of ADHD-related 
hyperactivity/impulsivity. 
 
To date, no stimulant trial has been conducted in an ASD population without ID. Results 
from stimulant trials for ADHD in youth with ID are inconclusive with reports of poor 
(Handen et al., 1990, 1991, 1992; Aman et al., 2003) to favorable response (Pearson et 
al., 2003, 2004, 2004). No data is available on the role of ID on the assessment of 
stimulant efficacy in children and adolescents with ASD. Nonetheless, the presence of 
ID may confound the outcome of stimulant trials for ADHD in ASD populations. 
 
Despite the overall lower tolerability to psychotropic medications demonstrated in ASD 
populations, there is no empirical evidence available on the treatment response to 
extended-release stimulant medications, which offer better tolerability due to a gradual 
mode of delivery. Clearly, there is a need for psychotheraputic agents with acceptable 
efficacy and tolerability profiles (taking into account mode of delivery) for the treatment 
of comorbid ADHD in individuals with ASD. 
 
Quillivant XR, an extended-release liquid formulation of methylphenidate hydrochloride, 
offers a gradual mode of delivery that may offer improved tolerability. The liquid 
preparation offers tremendous flexibility for initiating at a lower dose and for titration with 
smaller dose increments. In addition, the extended-release liquid preparation offers an 


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alternative mode of oral medication delivery for individuals who are incapable of 
swallowing pills. 
 
As individuals with ASD are more susceptible to adverse effects, require lower dose 
initiation and smaller dose titration, and are often unable to swallow pills due to sensory 
dysregulation, a liquid preparation of sustained-release MPH may offer better 
compliance and tolerability. Given that no empirical evidence on this medication in the 
referenced population is available, a systematic trial on the efficacy and tolerability of 
extended-release liquid-formulation MPH for the treatment of ADHD in intellectually 
capable individuals with ASD is warranted. 
 
2. SPECIFIC AIMS 
The purpose of this 6-week, flexible-titration, open-label study is to assess the 
tolerability, safety, and efficacy of methylphenidate hydrochloride extended-release 
liquid formulation (MPH-ERLF) for the treatment of attention-deficit/hyperactivity 
disorder (ADHD) in adults with high-functioning autism spectrum disorder (HF-ASD). 
Based on our central hypothesis that MPH-ERLF will be safe, tolerable, and effective in 
improving ADHD symptoms in adults with ASD, we propose to enroll up to 40 subjects 
of both genders ages 18-40 years with intact intellectual functions satisfying DSM-5 
criteria for both ASD and ADHD. 
 
Primary Objective:  
• To evaluate the efficacy of MPH-ERLF for the treatment of ADHD in adults with HF-
ASD 
Secondary Objectives:  
• To assess the safety and tolerability of MPH-ERLF short-term therapy in adults with 
HF-ASD 
• To study the treatment effect of MPH-ERLF short-term therapy on the social 
cognition and executive functions in adults with HF-ASD 
 
3. LENGTH OF STUDY 
This study will last up to 12 weeks from enrollment (allowing up to six weeks from the 
date of consent to schedule and complete the initial screening process). Once subjects 
have completed the screening process and baseline characterization, they will begin the 
6-week open-label trial. Subjects will be assessed on measures of efficacy and safety 
every week throughout the study. 
 
4. SOURCE OF SUBJECTS 
We plan to enroll up to 40 young adults in order to achieve the goal of exposing 20 
subjects to the study medication. Individuals who respond to local advertising will be 
screened for eligibility first by the study coordinator via phone and then in person by a 
study clinician. We also plan to recruit participants from the referral pool of existing and 
new patients attending a specialty clinic for ASD at the Massachusetts General 
Hospital, and through advertising in local and regional media via print ads, Internet ads, 
and advertising posters. Subjects may also be recruited from Facebook advertisements. 
These advertisements will link to a RedCap survey where interested participants can 


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submit their contact information so that a member of our staff can call or email them 
with more information.  Alternatively, our contact information will be provided so that 
they may call or email us directly. Our study staff will complete a study-specific phone 
screen with all interested participants. Participants who meet eligibility criteria will then 
be brought in to meet with a study clinician who will explain the study in detail and 
complete the informed consent process. 
 
The Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum 
Disorder is a specialized ambulatory care program devoted to the assessment and 
treatment of individuals of all ages with ASD. It is one of only a few programs in the New 
England area to offer comprehensive assessment for individuals with ASD, including a 
complete psychiatric evaluation, psychopharmacological, neuropsychological, 
behavioral, and social services consultation, psycho-educational support and 
cognitive/behavioral therapies. The ambulatory care team consists of board-certified 
psychiatrists specialized in the assessment and management of ASD. Adults with ASD, 
the majority of whom are individuals with intact intellectual capacity and language skills, 
make up approximately one-third of the ASD population attending the clinic. 
 
If a potential subject’s clinician ascertains that the patient has an interest in study 
participation, the clinician will offer contact information for the study coordinator to the 
patient. The patient can then contact the study coordinator for more information on the 
trial. All subjects that enter the study will undergo standard screening and diagnostic 
procedures. Clinical records are not scanned in order to recruit subjects. Patients who 
potentially meet criteria for the study will only be contacted by their treating clinician and 
referred should the patient decide they wish to participate. If a patient of an investigator 
decides to enroll in the trial, the process of informed consent will be conducted with a 
co-investigator who does not treat the patient in a clinical setting. Under no 
circumstances will a physician investigator obtain informed consent from his or her own 
patient. 
 
Subjects who have completed a previous medication trial in our program may be eligible 
to participate in this study, as described in the Study Design section. Other medical 
records on a subject will not be used at any point during this study. 
 
5. SUBJECT ENROLLMENT 
Informed consent/assent will be obtained prior to the performance of any protocol 
procedures including administration of study drug. The informed consent and assent 
documents will be used to explain, in simple terms, the risks and benefits of study 
participation to the subject. The Informed Consent Form will include an area where legal 
guardians or authorized representatives can provide informed consent for eligible 
dependents. In addition to the "Guardian and Authorized Representative for Adult" 
signature line, a line of Assent will be provided for study-participants between the ages 
of 18 and 40 who have legal representatives. The nature of the study will be fully 
explained to the subjects and/or their legal representative by a board-certified physician 
who is either the principal investigator or a co-investigator. The subjects and/or their 
legal representative will be encouraged to ask questions pertaining to their participation 


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in the study and the subject may take as much time as they feel necessary to consider 
their participation in the study and to consult with family members or their physician. 
Participation in this study is voluntary and subjects may withdraw from the study at any 
time. The IRB-approved informed consent/assent documents will be signed and dated 
by the subject and/or the subject’s legal representative and the physician obtaining 
consent. 
 
6. SUBJECT SELECTION CRITERIA 
 
A. 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.  
 
B. 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 determined per clinician judgment informed by a 
comprehensive review of subjects’ initial psychiatric evaluation and clinical 
assessment.  
• 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.  


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• 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. 
 


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7. DESIGN 
 
All data will be collected and entered into StudyTRAX, an electronic data capture 
system that streamlines data collection and ensures data integrity. StudyTRAX software 
allows researchers to design and implement study surveys electronically for collecting, 
storing, retrieving, and manipulating data. 
Participants and/or research staff will enter survey responses into electronic 
assessment forms using computers at the research site. The responses will then be 
transmitted securely via an encrypted connection and stored in a secured 
database. Electronic data capture eliminates the need for subsequent data entry by 
staff, thus minimizing human error. However, in the event that StudyTRAX is 
malfunctioning, study staff will print all study instruments and study data will be collected 
in paper form.  
Primary outcome measure will be reduction in ADHD symptoms as measured by 
change from baseline on the clinician-rated AISRS. Responders will be defined as those 
who demonstrate a ≥30% reduction in AISRS total score and CGI-ADHD-Improvement 
score ≤2.  Safety and tolerability will be assessed by the monitoring of spontaneous 
treatment-emergent adverse events with the Clinician-rated Treatment-emergent 
Adverse Events Log (CTAE). 
 
Secondary outcome measures will assess for treatment-related changes in 
associated psychopathology, social cognition, executive functions, and safety and 
tolerability: 
 
• Changes in autistic symptoms as reflected by CGI-ASD and SRS-2 (Informant 
Report) and SRS-2 (Self-Report). 
• Changes in executive functions and social cognition as reflected by CANTAB, WAIS-
IV, BRIEF-A, and DANVA2. 
• Safety and tolerability will be further assessed by monitoring for: 
a) Anxiety symptoms as reflected by HAM-A 
b) Obsessive/compulsive symptoms as reflected by Y-BOCS 
c) Depressive symptoms assessed by HAM-D 
d) Mania symptoms as reflected by YMRS 
     e) Psychotic symptoms as reflected by BPRS 
 
Dosing 
MPH-ERLF will be titrated to the target daily dose during the first three weeks of the trial 
(dose optimization phase). Titration of study medication will be guided by the following 
flexible titration schedule, as well as by tolerability to MPH-ERLF per clinician judgment. 
Week 3 and onwards, subjects will be maintained on maximum achieved dose with a 
one-time option to decrease the dose of the study medication to the next lowest 
available dose per clinician judgment based on tolerability to MPH-ERLF. Based on the 
tolerability and safety reported by MPH-ERLF trials in youth with ADHD, the following 
MPH-ERLF titration schedule is proposed: 
 


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Flexible Titration Schedule 
 Week 
Day 
Dose (mg) 
0 
0 
5 
0.5 
4 
10 
1 
8 
20 
1.5 
11 
30 
2 
15 
50 
2.5 
18 
60 
3-6 
22-42 
Maintain on 
maximum 
achieved dose 
 
Enough study medication for 9 days of dosing will be dispensed at each weekly visit. To 
assess and ensure drug accountability and compliance, study medication will be 
returned and re-dispensed by the study clinician at every visit.  
 
At each visit during the titration period, participants will be given a dosing schedule for 
the week, outlining daily dosing instructions and highlighting when a mid-week dose 
increase is scheduled to occur (barring any adverse events). Contact information of the 
principal investigator and co-investigators will be listed on the dosing schedule, and 
participants will be instructed to call or page if they are ever uncertain about dosing or 
experience any adverse events. 
 
Additionally, the study coordinator will complete scheduled compliance phone check-ins 
each week during the titration period. These phone calls will be made the day before a 
scheduled dose increase in order to remind subjects of the scheduled mid-week up-
titration. If, during the call, participants express concern about dosing or adverse events, 
the coordinator will transfer the call to a study clinician who will assess whether any 
dosing adjustments are needed.   
 
Concomitant Medications/Treatments 
As part of the initial psychiatric evaluation, a detailed history of past and present 
treatments (pharmacological and non-pharmacological) will be obtained. At each study 
visit, subjects will be assessed for the use of concomitant medication. The guidelines for 
use of concomitant medications/treatments during the study are as follows: 
• Participants may continue treatment with concomitant psychotropic medications 
(provided no exclusion criteria are met) and must remain on a stable dose during the 
course of the trial. 
• Subjects may take melatonin (up to 3 mg) or Benadryl (up to 50 mg) at bedtime as 
needed (prn) for insomnia. 
• Subjects requiring initiation of acute or chronic medication treatment may be 
discontinued from the study if treatment is judged by the investigator to interfere with 
the assessment of study drug effect. 
• Non-pharmacological treatments such as supportive individual, family, or group 
therapy will be permitted provided they were in place for a substantial period of time 


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(>1 month) prior to study enrollment and remain unchanged during the course of the 
trial. 
• No new non-pharmacological treatments may be initiated during the course of the 
trial.  
 
Screening Process (Week 99) 
The screening process will last up to 4 hours in total (involving up to 2 visits) and 
includes the following components: 
 
• Subjects will meet with a study clinician for a psychiatric evaluation and review of 
medical history.  
• The study clinician will ask the participant about his or her symptoms of autism 
spectrum disorder. 
• A study clinician will conduct a brief physical examination. 
• Female participants of childbearing potential will complete a urine pregnancy test. If 
a participant has a positive pregnancy test, she will not be able to take part in the 
study. The study doctor will inform the participant and discuss the clinically 
appropriate course of action. The participant will be offered 3 follow-up visits.  
• Participants will be required to give a urine sample to test for certain types of drugs. 
This includes prescription drugs, illegal drugs, and controlled substances 
(substances that may be habit-forming) that may affect behavior and that may be 
regulated by law. Results of the drug screen will be conveyed to the participant by 
the study clinician. If the results are positive for drug(s), there will be further 
discussion with the participant to determine if their continued participation in the trial 
is appropriate.       
• An electrocardiogram (ECG) will be conducted.  
• Blood will be drawn for laboratory tests. Clinical laboratory testing will consist of a 
comprehensive metabolic panel (electrolytes, liver function tests, thyroid function 
tests, glucose) and a complete blood count (CBC). The total amount of blood we will 
draw in this study is about 2 tablespoons. 
• The participant’s vital signs (blood pressure, heart rate, and weight) and height will 
be measured.  
• We will ask the participant to complete a questionnaire about their ASD symptoms 
(SRS-2). This questionnaire takes approximately 5-10 minutes to complete. 
• We will ask the participant to complete a brief demographic interview collecting 
information regarding socioeconomic status and history of head injury or trauma. 
This will take about 5-10 minutes to complete. 
• The participant will complete cognitive testing (WASI) to estimate full-scale IQ. This 
testing will take about 30 minutes to complete. 
• A trained psychometrician will conduct the K-SADS-E ADHD module with the 
participant to confirm diagnosis of ADHD. This will take about 30 minutes to 
administer. 
• A trained psychometrician will conduct the ADOS with the participant to confirm 
diagnosis of ASD. This will take about 1 hour to administer.  
 


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We anticipate that subjects may enter this trial following completion of/withdrawal from 
other protocols in our office, and that there may be procedural overlap. So as to not 
burden subjects/parents/guardians with redundant time commitments, we will use the 
following diagnostic data previously collected:  If a subject has completed an evaluation 
with one of the study clinicians in the three years preceding their entrance to the study, 
they will not be asked to repeat these overlapping diagnostic procedures. We will use 
the study diagnostic data previously collected so as to not burden the subject with 
redundant time commitments. However, the study clinician will review the interval time 
period to assess for clinically significant medical or psychiatric history to ensure that the 
subject meets appropriate study entrance criteria.   
 
If the subject has completed the WASI or WAIS-IV in the 12 months preceding their 
entrance into this study, subjects will not be asked to repeat these procedures. We will 
use the data previously collected so as not to burden the subject with redundant time 
commitments. 
 
Study participants and/or their legal guardians may request the results of their cognitive 
testing. In this case, the subject will receive a letter providing a basic interpretation of 
the results and referring them to the department’s surpervising neuropsychologist for 
any questions or concerns.  
 
Washout Period 
After the screening period, subjects who are currently taking prohibited medications and 
willing to discontinue the use of their medication may do so in order to be eligible for 
participation in this study, if clinically appropriate per clinician judgment. Due to the 
increased risk for psychosis upon discontinuation of an antipsychotic and initiation of a 
stimulant, first- or second-generation antipsychotic medications will not be discontinued 
for the purposes of initiating this trial. If appropriate, medication washout will be 
recommended by our clinicians to participants and current providers. Clinicians will 
determine a washout schedule based on the half-life of the medication, the adverse 
effects associated with treatment and withdrawal, and an assessment of individual 
factors including duration on drug and dose. Our office does not take over care for the 
patient, but remains available during this time period. The washout schedule will be 
discussed with the participant and current providers.  
 
Study Visits (Weeks 0 through 6) 
Study visits will have a visit window of +/- 2 days to facilitate scheduling. Although every 
effort will be made to encourage subjects to keep regularly scheduled appointments, in 
the event that a subject is unable to come into the office within a reasonable timeframe 
of a scheduled visit, and the treating research clinician feels that subject safety will not 
be jeopardized by doing so, the clinician can conduct the visit with the subject and 
parent/guardian over the phone. This will ensure that each subject will be continuously 
monitored by the clinician throughout the course of the study despite unforeseen 
scheduling circumstances. The following study visits cannot be conducted over the 
phone: Screening Visit (Week 99), Baseline (Week 0), Week 3, and Week 6. 
Additionally, phone visits may not occur for two consecutive visits. 


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During study visits: 
• A study doctor will ask the participant questions about the participant’s ASD 
symptoms and general health. The study doctor will also ask if the participant is 
having any side effects, and if they have taken any other medications during the 
previous week (see Table I for details). 
• We will measure participant’s blood pressure, heart rate, and weight. Participant’s 
height will measured at Week 6. 
• We will ask the participant to fill out seven questionnaires at Weeks 0 and 6, and five 
questionnaires at Week 3. This will take approximately 30-40 minutes. At Weeks 1, 
2, 4, and 5, we will ask the participant to complete one questionnaire (approximately 
10 minutes). 
• Optional: If a parent/caregiver is available, we will ask them to complete two 
informant-rating scales assessing the subject’s social responsiveness (SRS-2) and 
the subject’s symptoms associated with ASD (MGH-SECS-I) at weeks 0, 3, and 6. 
• At Week 6, we will ask the participant for a urine sample in order to test for 
prescription drugs, illegal drugs, and controlled substances (substances that may be 
habit-forming). For female participants of childbearing potential, we will also test for 
pregnancy. 
• At Weeks 0 and 6, the participant will complete the following cognitive assessments: 
CANTAB, WAIS-IV, and DANVA 2. The total time for these assessments will be 
approximately 3 hours. 
• During the final study visit (Week 6), we will conduct another ECG, physical exam 
and blood draw.  
 
For quality control purposes, assessments completed during these visits may be 
recorded. These recordings will be used to monitor quality control and inter-rater 
reliability in this study. Each recording will be coded with subject initials and an 
identification number to maintain confidentiality. These recordings will be stored in a 
password-protected database or on an encrypted external hard drive stored in a locked 
filing cabinet in a secure office. 
 
Study Discontinuation 
A participant may withdraw consent at any time for any reason (e.g., lack of efficacy, 
adverse events, etc.). A subject may be withdrawn from the study at any time if any of 
the following conditions are met: 
• Worsening of ASD, ADHD, anxiety, depression, mania, OCD or psychosis, as 
determined per clinician judgment informed by a comprehensive review of subjects’ 
initial psychiatric evaluation chart notes and progress notes from prior study visits as 
well as current clinical assessment.   
• Subjects who experience intolerable adverse effects, and/or clinically significant 
laboratory values inconsistent with continuation in the study as determined by the PI.  
• Unstable psychiatric condition that clinically requires 1) treatment with prohibited 
concomitant psychotropic medications or 2) subjects requiring inpatient psychiatric 
admission. 
• Emergent suicidality 


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• Active substance abuse 
• Pregnancy 
• Allergic drug reaction 
• Non-compliance (less than 70% compliance for 2 visits or longer) 
• Failure to return medication for 2 consecutive visits 
• Failure to keep study appointments for more than 2 consecutive visits without 
justification 
• Clinical judgment of the investigator 
 
Those subjects who terminate study participation before the completion of the study will 
be asked to complete all tasks scheduled to take place on the final study visit at the time 
of study discontinuation. 
 
Subjects may receive three clinical follow-up visits at the completion of the study (or if 
they are required to discontinue for safety reasons), allowing adequate time for 
appropriate psychiatric referrals to treaters in their communities. Follow-up visits are 
optional and are at no cost to participants. These visits are not part of the clinical trial 
and no research data will be collected during follow-up. Subjects who fail to return 
medication for two consecutive visits, fail to keep study appointments, or are non-
compliant (less than 70% compliance for two weeks or longer) may be dropped from the 
study. These study subjects will be given a referral to treaters in their area but will not 
be offered three follow-up visits.   
 
If a subject would like us to forward their clinical history to his/her primary care 
physician, or a new clinician, we will forward any pertinent information with the proper 
completed release of information authorization form. If a subject who has come from the 
clinic of the investigator happens to drop out of the study, he or she will return to his or 
her treating physician. 
 
8. ASSESSMENTS (See Table I for an assessment schedule) 
Given the pharmacokinetics and pharmacodynamics of MPH, subjects will be evaluated 
at weekly intervals.  At each weekly visit, measures of safety and efficacy will be 
obtained using assessments of psychiatric symptoms and functioning (AISRS, CGIs, 
GAF), measures of adverse effects (CTAE), and vital signs. At the midpoint (Week 3) 
and final study visits (Week 6), additional clinician- and subject-rated assessments will 
be repeated (see below for details). 
 
Diagnostic Assessments 
(Administered at screening evaluation) 
• Structured Diagnostic Interview: The Kiddie-Schedule for Affective Disorders and 
Schizophrenia-Epidemiologic Version (K-SADS-E; Orvaschel 1994) is a semi-
structured diagnostic interview designed to assess current and past episodes of 
psychopathology in youth according to DSM criteria. Probes and objective criteria 
are provided to rate individual symptoms. It provides a standardized method of 
obtaining and recording symptoms necessary for the assessment of diagnostic 
categories. It can be effectively administered by clinicians or trained interviewers. 


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We will also collect ages of onset and offset for each disorder. The ADHD 
module of K-SADS-E will be administered in this trial for confirming the diagnosis 
of ADHD. 
• Autism Diagnostic Observation Schedule (ADOS; Lord et al.,1994): The ADOS is 
an instrument that allows diagnosis and assessment of autism across age, 
developmental level, and language skills. The assessment consists of a series of 
semi-structured tasks that involve social interaction between certified rater and 
subject. 
• MGH Autism Spectrum Disorder DSM-5 Diagnostic Symptom Checklist (MGH-
ASD-SCL): The range and severity of subjects’ ASD symptoms will be assessed 
with the clinician-administered MGH-ASD-SCL. This screening instrument 
adopted items from DSM-5 diagnostic criteria for ASD and assesses for the 
individual core domains and associated features of ASD. 
 
Cognitive Assessments 
(Administered at screening evaluation) 
• Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-II; Wechsler, 
2011): Vocabulary and Matrix subtests will be administered. This scale meets the 
demand for a quick reliable measure of intelligence and determines verbal, 
performance, and full-scale IQ scores.  
• Wechsler Adult Intelligence Scale (WAIS-IV; Wechsler 2008): Digit Span, 
Arithmetic, and Letter/Number Sequencing subtests will be administered to 
assess working memory; Digit/Symbol Coding and Symbol Search subtests will 
be administered to assess processing speed. 
 
(Administered at baseline and final study visit)  
• Cambridge Neuropsychological Test Automated Battery  (CANTAB; Cambridge 
Cognition Limited, 2004): The CANTAB is designed to assess executive   
 
functioning. The subtests we use are not sensitive to practice effects. Subtests   
will include the following:  
 -Working Memory and Planning: 
-Spatial Working Memory (SWM): tests comprehension, learning,   
 
 
and reversal. 
-Stockings of Cambridge (SOC): assesses spatial planning and  
 
 
 
motor control. 
-Attention  
-Intra-Extra Dimensional Set Shifting (IED): tests rule acquisition  
 
 
 
and attentional set shifting.  
-Reaction Time (RTI): measures speed of response. 
-Rapid Visual Information Processing (RVP): tests sustained visual   
 
 
attention. 
-Response Control  
-Affective Go/No-Go (AGN): assesses information processing 
 
 
 
biases for positive and negative stimuli. 
-Verbal Memory 


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-Verbal Recognition Memory (VRM): assesses immediate free 
 
 
 
recall, and immediate and delayed recognition memory.  
• Diagnostic Analysis of Nonverbal Accuracy Scale (DANVA2; Nowicki & Carton, 
1993): The DANVA 2 consists of tasks of social competence, testing subjects’ 
 
ability to recognize feelings expressed through faces and paralanguage by adults  
and children. Child and Adult Facial Expressions subtests are used to assess 
 
face-emotion labeling. Each computer-administered subtest includes 24 
 
 
photographs of child or adult models (12 female, 12 male per subtest) displaying   
equal numbers of high- and low-intensity expressions of happiness, sadness, 
 
anger, and fear. Faces appear for 2 seconds. In a forced-choice format, 
 
 
participants indicate by button-press which emotion a face expresses. Both 
 
subtests have been standardized and have acceptable internal consistency and  
reliability (Nowicki & Carton, 1993; Constantino et al., 2000). Participants will 
 
complete Adult Faces and Adult Paralanguage subtests. 
 
Clinician-Rated Behavioral Measures 
(Administered at baseline, weekly study visits, midpoint, and endpoint)  
• Adult ADHD Investigator Symptom Report Scale (AISRS; Spencer et al., 2010): 
The AISRS, shown to be sensitive to drug effects in adult populations, assesses 
each of the 18 individual criteria symptoms of ADHD in DSM-IV on a severity grid 
(0=not present; 3=severe; overall minimum score=0; maximum score=54). 
• Clinical Global Impression Scale (CGI; National Institute of Mental Health, 1985): 
The CGI is a measure of illness severity, improvement, and efficacy of treatment. 
The score for severity ranges from 1 (normal, not at all ill) to 7 (among the most 
extremely ill subjects). Improvement ranges from 1 (very much improved) to 7 
(very much worse). The effectiveness index measures to what extent the subject 
is experiencing therapeutic effects in conjunction with the level of adverse events 
they are experiencing. CGI scales will be used for the assessment of ADHD and 
ASD. 
• Global Assessment of Functioning Scale (GAF; Endicott et al., 1976): composite 
rating of an individual’s overall level of functioning (1= worst to 100 = best). 
(Administered at baseline, midpoint, and final study visits) 
• MGH Social-Emotional Competence Scale [Clinician-Rated Measure] (MGH-
SECS-C): This is a 37-item scale that assesses change in the frequency and 
severity of core and associated symptoms of ASD. 
• Yale-Brown Obsessive Compulsive Scale (Y-BOCS; Goodman et al., 1989): This 
is a clinician-rated 10-item scale (total range from 0 to 40), with subtotals for 
obsessions (items 1-5) and compulsions (items 6-10). The Y-BOCS has been 
shown to be both a reliable and valid measure of OCD symptomatology in adults 
as well as responsive to changes with treatment. 
• Hamilton Anxiety Scale (HAM-A; Hamilton, 1959): a rating scale used to assess 
anxiety. This questionnaire consists of 14 questions assessing these symptoms. 
Clinicians are asked to rate each symptom as absent, mild, moderate, severe, or 
very severe. 
• Hamilton Depression 


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• Young Mania Rating Scale (YMRS; Young et al., 1978): is an 11-item interview 
that queries the core symptoms of mania, including elevated mood, irritability, 
psychomotor agitation, hypersexuality, and aggressive behavior. The YMRS 
score ranges from 0-60 and asks about symptoms of the previous week. 
• Brief Psychiatric Rating Scale (BPRS; Overall & Gorham, 1988): a scale 
commonly used to assess overall psychopathology. The scale consists of 18 
items, each rated on a scale from 1 (symptom not present) to 7 (symptom 
extremely severe). 
 
Subject-Rated Behavioral Measures  
(Administered at screening evaluation) 
• Demographic Interview: This brief interview will collect information regarding 
socioeconomic status and history of head injury or trauma (Hollingshead, 1975). 
• Social Responsiveness Scale-Second Edition Self-Report (SRS-2; Constantino & 
Gruber, 2012): a 65-item rating scale completed by subjects that is used to 
measure the severity of autism spectrum symptoms as they occur in natural 
settings. 
(Administered at baseline, weekly study visits, midpoint, and endpoint) 
• Adult ADHD Self-Report Scale (ASRS; Adler et al., 2006): The 18-item ADHD 
Rating Scale will be completed to evaluate frequency of ADHD symptoms on a 
scale of 0 to 4. 
(Administered at baseline, midpoint, and final study visits) 
• Social Responsiveness Scale-Second Edition Self-Report (SRS-2; Constantino & 
Gruber, 2012): a 65-item rating scale completed by subjects that is used to 
measure the severity of autism spectrum symptoms as they occur in natural 
settings. 
• Behavior Rating Inventory of Executive Function-Adult Self-Report Version 
(BRIEF-A; Roth, Isquith, & Gioia, 2004): a 78-item rating scale to assess level of 
executive function deficits. 
• Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q; Endicott, 
Nee et al. 1993): a 16-item questionnaire to evaluate the degree of enjoyment 
and satisfaction experienced in eight areas of daily functioning. 
• Social Responsiveness Scale-Second Edition Informant-Report (SRS-2; 
Constantino & Gruber, 2012): a 65-item rating scale completed by 
parents/caregivers that is used to measure the severity of autism spectrum 
symptoms of the subjects as they occur in natural settings. 
• MGH Social-Emotional Competence Scale [Informant-Rated Measure] (MGH-
SECS-I): This is a 37-item scale that assesses change in the frequency and 
severity of core and associated symptoms of ASD. 
 
 (Administered at baseline and final study visits) 
• Social Adjustment Scale (SAS; Weissman and Bothwell 1976): a 54-item 
multiple-choice questionnaire to assess social functioning. 
• Driver Behavior Questionnaire (DBQ; Reason et al, 1990): A 24-item scale to 
assess driving behaviors and frequency of driving errors and violations. 
 


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Clinician-Rated Safety Measures 
(Administered at baseline, weekly study visits, midpoint, and endpoint) 
• Clinician-Rated Treatment Emergent Adverse Events Log (CTAE): to record any 
spontaneous adverse health events experienced during the study, along with 
duration, severity, cause, treatment, and outcome. 
• Concomitant Medications: to record additional medications taken during the 
study. 
 
9. DATA ANALYSIS 
Statistical Analysis 
Considering the open-label single group design, we will rely on comparisons of the 
participants’ performances at baseline prior to the initiation of treatment relative to their 
scores at the last assessment (completion/drop-visit). Thus, statistics for paired samples 
will be utilized. This design largely protects against the bias introduced by confounding 
factors. That is, since the same participants are tested on two occasions, all static 
confounding factors are perfectly balanced, and can have no impact on the findings. 
Bias can still result from time-varying factors that are not associated with the outcomes, 
but we are confident that any such factors will have a minimal impact on this study 
considering the duration of the trial. Specifically, we will employ Wilcoxon signed rank 
tests for continuous or discrete outcome measures, and McNemar’s test for binary 
outcomes. These tests are free from assumptions regarding the distribution of the 
outcome variables, which is appropriate since the scales we are proposing to utilize are 
not considered to have Gaussian distributions, and will not be amenable to parametric 
methods. 
 
10. SAFETY 
 
Consistent with good clinical practice, safety will be monitored at each study visit by a 
subject’s assigned clinician. This clinician will be available 24 hours a day by page. The 
principal investigator will supervise all study activities including ratings, reported 
adverse events, laboratory tests, and vital signs. All procedures have been designed to 
minimize subject discomfort, and no subject will be asked to engage in research 
procedures not outlined in the consent form.  
 
If a subject is withdrawn from the study due to adverse events, lack of response, or as a 
decision by the clinician, they will be offered open treatment for three months, giving 
adequate time for appropriate psychiatric care to be arranged.  
 
Blood Draw  
A topical anesthetic cream (EMLA) will be offered to subjects before blood draws. The 
dose of EMLA cream will not exceed administration guidelines based on subject age 
and weight. Subjects with sensitivity to local topical anesthetics will not receive EMLA 
cream.  If an infection does occur, it will be treated. 
 
Study Medication 


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Safety will be monitored through treatment-emergent adverse events and measuring 
change in vital signs through laboratory analyses. Subjects will be monitored for 
adverse events at each visit. All adverse events will be recorded. A subject may be 
dropped from the study or dosage may be decreased and timing of medication changed 
at any time due to adverse events. All adverse events will be reported to the PHRC 
according to PHRC guidelines. All concomitant medications will be assessed at every 
study visit. At screening, subjects with contraindicated concomitant medications will be 
given the option of discontinuing such medications (see Washout Period, pg. 10) or will 
be withdrawn from the study. 
 
11. CONFIDENTIALITY 
 
All research-related records initiated as a result of a subject’s participation in this study 
that reveal the subject’s identity will remain confidential except as may be required by 
law. While the results of the clinical laboratory blood testing will become part of a 
subject’s Massachusetts General Hospital medical record, they will not link the subject 
to participation in any research. Subjects will only be contacted regarding future studies 
if they indicate that they are interested in being contacted by initialing in the specific 
section of the consent form. 
 
12. RISKS AND DISCOMFORTS 
 
Frequent Adverse Events Related to Study Drug  
Methylphenidate hydrochloride for extended-release oral suspension (Quillivant XR) is a 
central nervous system (CNS) stimulant indicated for the treatment of attention-
deficit/hyperactivity disorder. Based on accumulated data from other methylphenidate 
products and limited clinical trial data on Quillivant XR in children with ADHD, common 
adverse reactions (≥2% and twice the rate of placebo) are decrease in appetite, weight 
loss, nausea, abdominal pain, dyspepsia, dry mouth, vomiting, insomnia, anxiety, 
nervousness, restlessness, affect lability, agitation, irritability, dizziness, vertigo, blurred 
vision, increase in blood pressure, tachycardia, increased sweating, fever, excoriation, 
tics, motion sickness, eye pain, and rash. 
 
Heart-related problems including sudden death, stroke, and myocardial infarction have 
been reported with use of MPH and other stimulant medications. CNS stimulants may 
exacerbate behavior disturbance or thought disorder in patients with a pre-existing 
psychotic disorder, may induce a manic or mixed episode in patients with bipolar 
disorder, and may induce manic or psychotic symptoms in patients without a prior 
history of mania/psychosis. There have been reports of priapism and peripheral 
vasculopathy, including Raynaud’s phenomenon, in association with MPH treatment. 
MPH is a federally controlled substance with high potential for abuse and dependence.  
 
All participants will be closely monitored for serious adverse reactions. All serious 
unexpected adverse events will be reported to the sponsor (Pfizer, Inc.) and the 
Partners Human Research Committee as stipulated by Pfizer and PHRC regulations. 
 


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Other Adverse Events Related to Study Drug 
Problems and side effects not listed above and not known at this time could occur. 
Subjects will be informed of any newly discovered risks as investigators come to learn 
of such knowledge, if applicable. 
 
Risks of Blood Draws 
When blood is drawn, some discomfort may occur. Bruising and/or bleeding at the 
needle site may occur. Occasionally a person feels faint. Rarely, an infection may 
develop. If an infection does occur, it can be treated. A topical anesthetic cream (EMLA) 
will be offered to subjects to numb the skin where blood will be drawn if subjects prefer. 
 
Risks of Assessments/Questionnaires 
Some questions may make subjects feel uncomfortable because of the nature of the 
question topics. Some questions ask about possibly sensitive information, including 
questions pertaining to alcohol and drug abuse. Subjects may refuse to respond to any 
questions they do not feel comfortable answering. 
 
Adverse events and unanticipated problems will be reported to the PHRC according to 
current guidelines. We will follow and adhere to all guidelines as defined and outlined on 
the Partners Human Research Committee web site: 
(http://healthcare.partners.org/phsirb/adverse_events.htm). 
 
13. POTENTIAL BENEFITS 
 
There may be no direct benefit to subjects participating in this study. Participants may 
benefit by potentially experiencing improvement in ADHD symptoms and by gaining 
knowledge about ASD and ADHD.  
 
 


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Table I. Study Schema 
Visits (Weeks) 
99 
0 
1 
2 
3 
4 
5 
6 
MPH-ERLF Dose Titration (mg/per day) 
 
5 
20 50 60* 60* 60* 60* 
Informed Consent 
X 
 
 
 
 
 
 
 
Diagnostic Assessments 
 
 
 
 
 
 
 
 
MGH-ASD-SCL 
X 
 
 
 
 
 
 
 
Psychiatric Evaluation & Medical History 
X 
 
 
 
 
 
 
 
ADOS 
X 
 
 
 
 
 
 
 
K-SADS-E ADHD Module 
X 
 
 
 
 
 
 
 
Physiological Procedures 
 
 
 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
 
X 
Urine pregnancy test (females only) 
X 
 
 
 
 
 
 
X 
Urine drug screen 
X 
 
 
 
 
 
 
X 
Hematological tests 
X 
 
 
 
 
 
 
X 
EKG 
X 
 
 
 
 
 
 
X 
Vital Signs (pulse, BP & weight) 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
X 
Cognitive Assessments 
IQ Assessment (WASI) 
X 
 
 
 
 
 
 
 
CANTAB, WAIS-IV, DANVA2 
 
X 
 
 
 
 
 
X 
Clinician-Rated Assessments 
AISRS 
X 
X 
X 
X 
X 
X 
X 
X 
MGH-SECS-C 
 
X 
 
 
X 
 
 
X 
CGI-ASD 
X 
X 
X 
X 
X 
X 
X 
X 
CGI-ADHD 
X 
X 
X 
X 
X 
X 
X 
X 
Y-BOCS 
 
X 
 
 
X 
 
 
X 
HAM-A 
 
X 
 
 
X 
 
 
X 
HAM-D 
 
X 
 
 
X 
 
 
X 
YMRS 
 
X 
 
 
X 
 
 
X 
BPRS 
 
X 
 
 
X 
 
 
X 
GAF 
 
X 
X 
X 
X 
X 
X 
X 
CTAE 
 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Patient-Rated Assessments 
Demographic Interview 
X 
 
 
 
 
 
 
 
ASRS 
 
X 
X 
X 
X 
X 
X 
X 
SRS-2 (Self) 
X 
X 
 
 
X 
 
 
X 
BRIEF-A 
 
X 
 
 
X 
 
 
X 
SAS 
 
X 
 
 
 
 
 
X 
DBQ 
 
X 
 
 
 
 
 
X 
Q-LES-Q 
 
X 
 
 
X 
 
 
X 
Informant-Rated Assessments 
SRS-2 (Informant) 
 
X 
 
 
X 
 
 
X 
MGH-SECS-I  
 
X 
 
 
X 
 
 
X 
 


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Methylphenidate ER Liquid Formulation in Adults with ASD+ADHD 
Version: Amendment 41 RtR, submitted to the IRB 12/09/2016  
 
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ICF_001.pdf: 
Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  October 2014 
 
Page 1 of 17 
 
Subject Identification 
Protocol Title: An 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 
 
Principal Investigator: Gagan Joshi, M.D. 
 
Site Principal Investigator:       
 
Description of Subject Population: Adults with autism spectrum disorder and 
ADHD (ages 18-40) 
About this consent form 
 
Please read this form carefully.  It tells you important information about a research study.  A 
member of our research team will also talk to you about taking part in this research study.  
People who agree to take part in research studies are called “subjects.”  This term will be used 
throughout this consent form. 
 
Partners HealthCare System is made up of Partners hospitals, health care providers, and 
researchers.  In the rest of this consent form, we refer to the Partners system simply as 
“Partners.” 
 
If you have any questions about the research or about this form, please ask us.  Taking part in 
this research study is up to you.  If you decide to take part in this research study, you must sign 
this form to show that you want to take part.  We will give you a signed copy of this form to 
keep. 
 
Some of the people who are eligible to take part in this study may not be able to give consent 
to take part because of their medical condition.  Instead we will ask the person’s authorized 
representative to give consent.  Throughout the consent form, “you” always refers to the 
person who takes part in the study. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you.  At most, the Web 
site will include a summary of the results.  You can search this Web site at any time. 
 
 
Consent Form Title: Quillivant Consent Form AME 41 CL.doc
IRB Protocol No: 2014P000501
Consent Form Valid Date: 6/15/2017
IRB Expiration Date: 4/8/2018
Sponsor Protocol No: Detailed Protocol AME 24
Sponsor AME No: N/A
IRB AME No: AME46






















Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  October 2014 
 
 
 
 
Page 12 of 17 
 
Subject Identification 
Taking part in this research study is up to you.  You can decide not to take part.  If you decide to 
take part now, you can change your mind and drop out later.  We will tell you if we learn new 
information that could make you change your mind about taking part in this research study. 
 
 
What should I do if I want to stop taking part in the study? 
 
If you take part in this research study, and want to drop out, you should tell us.  We will make 
sure that you stop the study safely.  We will also talk to you about follow-up care, if needed. 
 
Also, it is possible that we will have to ask you to drop out of the study before you finish it.  If 
this happens, we will tell you why.  We will also help arrange other care for you, if needed. 
 
 
Will I be paid to take part in this research study? 
 
We will not pay you to take part in this study. If you drive to study visits, we will give you a 
voucher to cover the cost of parking in the hospital garage. 
 
What will I have to pay for if I take part in this research study? 
 
Pfizer, Inc. is providing the study drug at no cost. 
 
Study funds will pay for the study visits, study drug, your medical and mental health evaluation, 
ECGs, lab tests, and all procedures done only for the research. 
If you choose to complete the 3 optional follow-up visits after the study is complete, the visits 
will be provided at no cost to you or your insurance. 
Study funds will pay for certain study-related items and services.  We may bill your health 
insurer for, among other things, routine items and services you would have received even if you 
did not take part in the research.  You will be responsible for payment of any deductibles and co-
payments required by your insurer for this routine care or other billed care.  If you have any 
questions about costs to you that may result from taking part in the research, please speak with 
the study doctors and study staff.  If necessary, we will arrange for you to speak with someone in 
Patient Financial Services about these costs. 
 
 
Consent Form Title: Quillivant Consent Form AME 41 CL.doc
IRB Protocol No: 2014P000501
Consent Form Valid Date: 6/15/2017
IRB Expiration Date: 4/8/2018
Sponsor Protocol No: Detailed Protocol AME 24
Sponsor AME No: N/A
IRB AME No: AME46


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  October 2014 
 
 
 
 
Page 13 of 17 
 
Subject Identification 
What happens if I am injured as a result of taking part in this research 
study?
 
 
 
We will offer you the care needed to treat any injury that directly results from taking part in this 
research study.  We reserve the right to bill your insurance company or other third parties, if 
appropriate, for the care you get for the injury.  We will try to have these costs paid for, but you 
may be responsible for some of them.  For example, if the care is billed to your insurer, you will 
be responsible for payment of any deductibles and co-payments required by your insurer. 
 
Injuries sometimes happen in research even when no one is at fault.  There are no plans to pay 
you or give you other compensation for an injury, should one occur.  However, you are not 
giving up any of your legal rights by signing this form. 
 
If you think you have been injured or have experienced a medical problem as a result of taking 
part in this research study, tell the person in charge of this study as soon as possible.  The 
researcher's name and phone number are listed in the next section of this consent form. 
 
 
If I have questions or concerns about this research study, whom can I 
call? 
 
You can call us with your questions or concerns.  Our telephone numbers are listed below.  Ask 
questions as often as you want.
 
Gagan Joshi, MD is the person in charge of this research study.  You can call him at (617) 726-
7899 (Mondays through Fridays from 9 am to 5 pm). Dr. Joshi is available 24 hours a day by 
pager by calling the hospital at (617) 726-2066 and asking for page # 38188.   
 
If you have questions about the scheduling of appointments or study visits, please call the study 
coordinator, Barbora Hoskova, at (617) 724-7301, Mondays through Fridays from 9 am to 5 pm.
 
If you want to speak with someone not directly involved in this research study, please contact 
the Partners Human Research Committee office.  You can call them at 857-282-1900. 
 
You can talk to them about: 
 Your rights as a research subject 
Consent Form Title: Quillivant Consent Form AME 41 CL.doc
IRB Protocol No: 2014P000501
Consent Form Valid Date: 6/15/2017
IRB Expiration Date: 4/8/2018
Sponsor Protocol No: Detailed Protocol AME 24
Sponsor AME No: N/A
IRB AME No: AME46






Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  October 2014 
 
 
 
 
Page 16 of 17 
 
Subject Identification 
Informed Consent and Authorization 
 
Statement of Person Giving Informed Consent and Authorization 
 
 I have read this consent form. 
 This research study has been explained to me, including risks and possible benefits (if 
any), other possible treatments or procedures, and other important things about the study. 
 I have had the opportunity to ask questions. 
 I understand the information given to me. 
 
 
Signature of Subject: 
 
I give my consent to take part in this research study and agree to allow my health information to 
be used and shared as described above. 
 
 
 
 
 
 
 
 
Subject 
Date 
Time (optional) 
 
 
 
Signature of Guardian or Authorized Representative for Adult: 
 
I give my consent for the person I am authorized to represent to take part in this research study 
and agree to allow his/her health information to be used and shared as described above. 
 
 
 
 
 
 
Print Name (check applicable box below) 
 Court-appointed Guardian 
 Health Care Proxy 
 Durable Power of Attorney 
 Family Member/Next-of-Kin 
 
 
 
 
 
 
 
 
Signature 
Date 
Time (optional) 
Consent Form Title: Quillivant Consent Form AME 41 CL.doc
IRB Protocol No: 2014P000501
Consent Form Valid Date: 6/15/2017
IRB Expiration Date: 4/8/2018
Sponsor Protocol No: Detailed Protocol AME 24
Sponsor AME No: N/A
IRB AME No: AME46


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  October 2014 
 
 
 
 
Page 17 of 17 
 
Subject Identification 
 
Relationship to Subject: 
 
 
 
 
 
 
 
 
 
 
Assent 
 
Statement of Person Giving Assent 
 
 This research study has been explained to me, including risks and possible benefits (if 
any), other possible treatments or procedures, and other important things about the study. 
 I have had the opportunity to ask questions, and my questions have been answered. 
 
Signature of Adult: 
 
I agree to take part in this research study and agree to allow my health information to be used 
and shared as described above. 
 
 
 
 
 
 
 
 
Adult 
Date 
Time (optional) 
 
 
Signature of Study Doctor or Person Obtaining Consent: 
 
Statement of Study Doctor or Person Obtaining Consent 
 
 I have explained the research to the study subject. 
 I have answered all questions about this research study to the best of my ability. 
 
 
 
 
 
 
 
 
Study Doctor or Person Obtaining Consent 
Date 
Time (optional) 
 
 
 
 
Consent Form Version:  AME 46, 05/30/2017 
 
Consent Form Title: Quillivant Consent Form AME 41 CL.doc
IRB Protocol No: 2014P000501
Consent Form Valid Date: 6/15/2017
IRB Expiration Date: 4/8/2018
Sponsor Protocol No: Detailed Protocol AME 24
Sponsor AME No: N/A
IRB AME No: AME46