Pharmacokinetic Study of DYANAVEL XR (Amphetamine) Extended-release Oral Suspension, in Children Aged 4 to 5 Years

DYANAVEL® XR is an extended-release oral suspension that contains 2.5 mg/mL amphetamine base
(amphetamine extended-release oral suspension; AMPH EROS). Drug-resin complexation is formed
with the amphetamine and sodium polystyrene sulfonate, an ion exchange resin. The extended
release feature of the product is achieved by coating a portion of the drug/resin complexes
with an extended release coating. AMPH EROS contains approximately a 3.2:1 ratio of
d-amphetamine compared to l-amphetamine.

The objective of this study was to evaluate the plasma amphetamine concentration/time profile
of AMPH EROS in children aged 4 to 5 years with attention-deficit/hyperactivity disorder,
following a single 2.5 mg dose of AMPH EROS.

These data will guide appropriate dosing in planned safety and efficacy studies with AMPH
EROS in a preschool population with attention-deficit/hyperactivity disorder.

Inclusion Criteria:

1. Male or female aged 4 to 5 years at the time of enrollment into this study;

2. Body weight ≥ 28 lb. at screening visit;

3. Diagnosed with ADHD by a psychiatrist, psychologist, developmental pediatrician,
pediatrician, or an experienced licensed allied health professional approved by the
Sponsor by using the DSM-5 criteria and supported by a structured Kiddie-Schedule for
Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL)
interview, administered at the Screening Visit (Visit 0);

4. Provide written informed consent (parent/guardian) prior to participation in the
study.

Exclusion Criteria:

1. Diagnosed with any DSM-5 active disorder (other than ADHD) with the exception of
specific phobias, learning disorders, motor skills disorders, communication
disorders,oppositional defiant disorder, elimination disorders, and sleep disorders

2. History of chronic medical illnesses including seizure disorder (excluding a history
of febrile seizures), moderate to severe hypertension, untreated thyroid disease,
known structural cardiac disorders, serious cardiac conditions, serious arrhythmias,
cardiomyopathy and known family history of sudden death

3. Known history or presence of significant renal or hepatic disease, as indicated by
clinical laboratory assessment (liver function test results ≥ 2 times the upper limit
of normal, blood urea nitrogen, or creatinine)

4. Clinically significant (CS) abnormal ECG or cardiac findings on physical examination
(including the presence of a pathologic murmur)

5. Use of the following medications within 30 days of dosing:

- MAOI - monoamine oxidase inhibitors (e.g., Selegiline, isocarboxazid, phenelzine,
tranylcypromine);

- Tricyclic Antidepressants (e.g. Desipramine, protriptyline);

6. Use of the following medications within 3 days of dosing

- Gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid
HCl, ascorbic acid);

- Urinary acidifying agents (e.g., ammonium chloride, sodium acid
phosphate,methenamine salts);

7. Use of atomoxetine within 14 days of dosing

8. Planned use of prohibited drugs or agents from the screening visit through the end of
the study. Medications used to support sleep may be acceptable with the written
approval of the sponsor or medical monitor

9. Abnormal CS laboratory test value at screening that, in the opinion of the sponsor or
medical monitor, would preclude study participation

10. Known history of allergy/hypersensitivity to amphetamine or any of the components of
AMPH EROS, heparin flush and topical anesthetics

11. Parent or guardian's inability or unwillingness to follow directions of the
Investigator or study research staff

12. Any uncontrolled medical condition that in the opinion of the Investigator would
preclude study participation

13. History of significant illness requiring hospitalization, or surgery requiring
anesthetics within 30 days of dosing.