A 12-Month Open Label Safety Study of Aptensio XR® in Children Ages 4-5 Years Diagnosed With ADHD

There are several pathways by which subjects enter the 12-month Maintenance Phase of this
long-term safety study:

- Subjects may have previously participated in one of two studies where: (i) an optimized
dose of Aptensio XR® was directly determined (Study RP-BP-EF003) or (ii) an optimized
dose of Aptensio XR® was inferred (Study RP-BP-PK003) . Henceforth, these Studies and
Subjects will be referred to as Prior Studies and Ongoing Subjects, respectively.

- Subjects may be naïve to Aptensio XR®, and will undergo a dose optimization phase in
this study prior to beginning the long-term maintenance phase (New Subjects).

Male and female children with a diagnosis of ADHD (combined, inattentive or
hyperactive/impulsive type) based on the Diagnostic and Statistical Manual of Mental
Disorders Fifth Edition (DSM-5) criteria, who were 4 to less than 6 years of age at time of
consent for Prior Studies, will be enrolled. New Subjects with a diagnosis of ADHD (based on
the DSM-5) must be at least 4 and less than 6 years of age at the time of consent for this
study. For new subjects, ADHD-RS IV ratings obtained at screening will include the 6-months
immediately prior to screening.

There will be four phases in this study (i) a screening phase, (ii) a dose optimization
phase (New Subjects, only), (iii) a dose maintenance phase and (iv) a follow-up phase.
Ongoing Subjects will complete the Screening/Baseline assessments the same day as the End of
Study Visit from a Prior Study and begin Aptensio XR® at their previously determined optimal
dose. New Subjects will complete the Screening/Baseline assessments and begin Aptensio XR®
after all eligibility criteria have been met.

New Subjects will initially receive Aptensio XR® 10 mg capsules. The dose may be
subsequently increased on a weekly basis to 15, 20, 30, 40, 50 or 60 mg based on responses
measured by the ADHD-RS-IV Preschool Version and tolerability. The dose may be decreased if
tolerability issues arise. Subjects who cannot tolerate Aptensio XR® 10 mg will be
discontinued from the trial. Once an optimal dose is achieved and observed for 2 weeks, New
Subjects will enter the dose maintenance phase.

Visits will occur every four weeks for 12 months during treatment with Aptensio XR®. At the
investigator's discretion, Aptensio XR® dose may be titrated during this phase to sustain
optimal clinical response.

Approximately two weeks after the final study visit or treatment discontinuation, a
follow-up phone call will be made to assess for ongoing adverse events and concomitant
medications.

Approximately 120 subjects will be enrolled in this trial.

Inclusion Criteria:

- Male and female subjects aged 4 to less than 6 years inclusive at the time consent
was given to participate in Prior Studies. New Subjects must be at least 4 years but
less than 6 years of age when written consent is given to participate in this trial.

- Meets DSM-5 criteria for ADHD, combined, hyperactive/impulsive or inattentive
presentation diagnosed during a clinical interview by an experienced clinician, and
confirmed with Kiddie-Sads-Present and Lifetime Version (K-SADS-PL) during Prior
Studies or at the screening visit for the current trial

- Subjects who completed the pre-school pharmacokinetic study (RP-BP-PK003) must meet
the following criteria (Note: these data are collected during methylphenidate washout
for RP-BP-PK003): (i) Age- and sex-adjusted ratings of 90th percentile Total Score on
the ADHD-RS-IV Pre-school version, (ii) A score of <65 on the Child Global Assessment
(CGAS) and (iii) A score of ≥4 on the Clinical Global Impressions-severity (CGI-S)
scale

- Subjects who have not participated in Prior Studies must also meet the following
criteria: (i) ADHD symptoms must have been present for at least 6 months, (ii)
Subject has undergone a course of behavior therapy for ADHD or ADHD symptoms are
severe enough to warrant medication treatment without prior behavior treatment, (ii)
Age- and sex-adjusted ratings of ≥ 90th percentile Total Score on the ADHD-RS-IV
Preschool Version Score of <65 on the Child Global Assessment , (iii) Must have a
score of ≥4 on the Clinical Global Impressions-Severity (CGI-S) at Visit T1, (iv)
Estimated IQ ≥80 on the Kaufman Brief Intelligence Test (KBIT-2), (v) Laboratory
values and ECG results that are normal or not clinically-significant at screening,
(vi) Urine drug screen that is negative except for prescribed stimulant medication

- The subject has a parent or legal guardian who will give written informed consent for
the subject to participate in the study

- Subject must give written assent to participate in the study (if applicable)

- Subject and parent/legal guardian must be able to speak and understand English

- Subject and parent/legal guardian must be willing to comply with all study
requirements

- Systolic and diastolic blood pressure below the 95th percentile for age and gender

- Subject must have lived with same parent or guardian for at least six months

Exclusion Criteria:

- The subject has had a lack of response to a trial of adequate dose and duration of
MPH or intolerance to previous (MPH) treatment

- The subject is using any other current psychotropic medication except stimulants or
has taken an investigational drug (other than Aptensio XR® in an antecedent trial) in
the 30 days prior to screening

- The subject has used monoamine oxidase inhibitors within 14 days of the screening
visit

- The subject plans to use prohibited drugs or agents at any point between the
screening visit and the end of the study

- Use of anticonvulsants, antidepressants or antipsychotics in the 30 days prior to
screening

- The subject has a history of chronic vocal or motor tics or Tourette's syndrome

- The subject has any clinically-significant ECG abnormalities at screening

- The subject has any major medical conditions that would interfere with involvement in
a study or could be affected negatively by methylphenidate

- The subject has chronic medical illnesses including a seizure disorder (excluding a
history of febrile seizures), severe hypertension, untreated thyroid disease, known
structural cardiac abnormalities, serious arrhythmias, cardiomyopathy, glaucoma, or a
family history of sudden death

- History (in the preceding 12 months) or presence of clinically significant
cardiovascular, cerebrovascular, renal, hepatic, gastrointestinal, pulmonary,
immunological, hematological, endocrine, or neurological disease that in the opinion
of the investigator could put the subject at risk if he/she participates in the trial
or could confound study results

- Family history (parent or sibling) of structural cardiovascular disease

- Current or recent (past 12 months) history of drug abuse in someone living in the
subject's home

- Current symptoms or history of major psychiatric illness (for example schizophrenia,
psychosis, bipolar disorder, post-traumatic stress disorder, depression, severe
anxiety disorder, obsessive compulsive disorder or autistic spectrum disorder) in
addition to ADHD that requires treatment with additional medication or, in the
opinion of the PI, would contraindicate study participation

- History or presence of suicidal ideation or significant self-injurious behavior

- The subject shows evidence of current physical, sexual, or emotional abuse

- Both biological parents of the subject have a history of bipolar disorder

- Non-compliance during Prior Studies