Safety, Tolerability and Pharmacokinetics of SHP465 in Children Aged 4 to 5 Years With Attention-Deficit/Hyperactivity Disorder (ADHD)

A Phase 1 Open-label Study of the Safety, Tolerability, and Pharmacokinetics of d- and l-Amphetamine After Multiple Daily Doses of SHP465 6.25 mg Administered in Children Aged 4 to 5 Years With Attention-Deficit/Hyperactivity Disorder

The purpose of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of SHP465 in children aged 4 to 5 years with ADHD after multiple daily doses of 6.25 milligram (mg) SHP465

Inclusion Criteria:

1. Male or female aged 4-5 years inclusive at the time of consent with a primary diagnosis of ADHD (any subtype) based on a detailed psychiatric evaluation using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and has undergone nonpharmacological treatment or has a severe enough condition to consider enrollment without undergoing prior nonpharmacological treatment, based on the investigator's judgment or has never taken ADHD medication or has taken ADHD medication with unacceptable efficacy and/or tolerability.

2. Participant's parent/legally authorized representative (LAR) must sign the informed consent form, and there must be documentation of assent (if applicable) and is willing and able to fully comply with all of the testing and requirements defined in the protocol.

3. Participant during the screening period:

   i. Has a total score of ADHD-RS-5 >=28 for boys and >=24 for girls. ii. Has a Clinical Global Impressions-Severity of Illness (CGI-S) score >=4. iii.Functions at an age-appropriate level intellectually, as determined by the investigator.

4. Participant has the ability to take investigational product by either swallowing the capsule whole or sprinkling the capsule contents in applesauce and ingesting the entire mixture immediately without chewing.

5. Participant has lived with the same parent/LAR for at least 6 months.

Exclusion Criteria:

1. Prior enrollment or participation in the study.

2. Documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.

3. Participant cannot swallow a pill and/or applesauce, or has an allergy to applesauce.

4. Participant is currently taking or has taken ADHD medication with acceptable efficacy and tolerability.

5. Participant has taken ADHD medication within 7 days prior to the administration of investigational product.

6. Participant has used any medication (including over-the-counter, herbal, or homeopathic preparations) within 30 days prior to the administration of investigational product or 5 half-lives, whichever is longer, with the exception of the following:

   i. Thyroid medication ii. Intermittent use of nonsteroidal anti-inflammatory drugs or acetaminophen iii. As needed use of a beta-agonists inhaler for mild asthma or exercise induced bronchospasm iv. Over-the-counter nonsedating antihistamines for allergies. v. Participant has continuously used oral corticosteroids >=7 days in 3 months prior to investigational product dosing. If continuous use was less than (<) 7 days, 1 month of washout prior to dosing of investigational product is required.

7. Within 30 days prior to the administration of investigational product (IP):

   i. Participant has used an IP.

   1. If the elimination half-life of the previous study's IP was less than 6 days, then the last dose of the previous IP should be 30 days prior to the first dose of SHP465.
   2. If the elimination half-life of the previous study's IP was greater than 6 days, then the last dose of the previous IP should be 5 half-lives prior to the dose of SHP465.

8. Glaucoma.

9. Known family history of sudden cardiac death or ventricular arrhythmia.

10. Known history of symptomatic cardiovascular disease, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac conditions placing them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

11. Any clinically significant ECG or clinically significant laboratory abnormalities at the first screening visit based on the investigator's judgment. A single retest of laboratory parameters is allowed based on the investigator's judgment.

12. Marfan's syndrome.

13. Blood pressure >= 95th percentile for age, sex, and height at the screening visit.

14. Height and weight <= 5th percentile for age and sex at the first screening visit.

15. Current abnormal thyroid function test results, defined as abnormal thyroid-stimulating hormone, thyroxine (T4), and tri-iodothyronine (T3) at the first screening visit. Treatment with a stable dose of thyroid medication for at least 3 months is permitted.

16. History of seizures (other than infantile febrile seizures).

17. Current, controlled (requiring medication or therapy) or uncontrolled, comorbid psychiatric disorder including but not limited to any of the following comorbid Axis I disorders and Axis II disorders.

18. Currently considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or has a prior history of or is currently demonstrating active suicidal ideation.

19. History of physical, sexual, or emotional abuse.

20. Primary sleep disorder (eg, sleep apnea, narcolepsy).

21. Eating disorder.