Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder (ADHD)

Shire

Status and phase: Completed; Phase 3

Conditions: Attention Deficit Hyperactivity Disorder (ADHD)

Treatments: Drug: SPD489 (Lisdexamfetamine dimesylate); Drug: SPD489; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03260205

SPD489-347

Details and patient eligibility

About

The purpose of this study is to determine if an investigational treatment is effective in improving the total score on the ADHD-RS-IV Preschool Version in children 4-5 years old diagnosed with ADHD.

Enrollment: 199 patients

Sex: All

Ages: 4 to 5 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant is a male or female aged 4-5 years inclusive at the time of consent
• Participant's parent(s) or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the participant before completing any study related procedures.
• Participant and parent(s)/LAR are willing and able to comply with all of the testing and requirements defined in the protocol, including oversight of morning dosing.
• Participant must meet DSM-IV-TR criteria for a primary diagnosis of ADHD (any sub-type).
• Participant has an ADHD-RS-IV Preschool Version Total Score at the baseline visit (Visit 0) greater than or equal to 28 for boys, and greater than or equal to 24 for girls.
• Participant has a Clinical Global Impressions - Severity of Illness (CGI-S) score greater than or equal to 4 at the baseline visit (Visit 0).
• Participant has a Peabody Picture Vocabulary Test standard score of greater than or equal to 70 at the screening visit (Visit -1).
• Participant has undergone an adequate course of non-pharmacological treatment or has a severe enough condition to consider enrollment without undergoing prior non-pharmacological treatment.
• Participant has participated in a structured group activity (e.g, preschool, sports, Sunday school) so as to assess symptoms and impairment in a setting outside the home.
• Participant has lived with the same parent(s) or guardian for greater than or equal to 6 months.

Exclusion criteria

• Participant is required to or anticipates the need to take any prohibited medications or medications that have central nervous system (CNS) effects or have an effect on performance. Stable use of bronchodilator inhalers is not exclusionary.

• Participant has taken another investigational product or has taken part in a clinical study within 30 days prior to the screening visit (Visit -1).

• Participant is well-controlled on his/her current ADHD medication with acceptable tolerability.

• Participant has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments or may increase risk to the participant..

• Participant has glaucoma.

• Participant has failed to fully respond to an adequate course of amphetamine therapy.

• Participant has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.

• Participant has a known family history of sudden cardiac death or ventricular arrhythmia.

• Participant has a blood pressure measurement greater than or equal to 95th percentile for age, sex, and height at the screening visit (Visit -1) or the baseline visit (Visit 0) or history of moderate or severe hypertension.

• Participant has a known history of symptomatic cardiovascular disease, unexplained syncope, exertional chest pain,advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.

• Participant has any clinically significant clinical laboratory abnormalities at the screening visit (Visit -1) or electrocardiogram (ECG) at screening visit (Visit-1) or baseline visit (Visit 0) based on investigator judgment.

• Participant has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4) at the screening visit (Visit -1). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.

• Participant has a current, controlled (requiring medication or therapy) or uncontrolled, co-morbid psychiatric disorder including but not limited to any of the below co-morbid Axis I disorders and Axis II disorders:

  i. post-traumatic stress disorder or adjustment disorder ii. bipolar illness, psychosis, or a family history of these disorders iii. pervasive developmental disorder iv. obsessive-compulsive disorder (OCD) v. psychosis/schizophrenia vi. a serious tic disorder, or a family history of Tourette's disorder vii. Participant is 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.

viii. a history of physical, sexual, or emotional abuse ix. any other disorder or agitated state that in the opinion of the investigator, contraindicates SPD489 or lisdexamfetamine dimesylate treatment or confound efficacy or safety assessments.

• Participant has initiated behavioral therapy within 1 month of the baseline visit (Visit 0). Participant may not initiate behavioral therapy during the study.
• Participant has a height less than equal to (<=) 5th percentile for age and sex at the screening visit (Visit -1).
• Participant has a weight <= 5th percentile for age and sex at the screening visit (Visit -1).
• Participant lives with anyone who currently abuses stimulants or cocaine.
• Participant has a history of seizures (other than infantile febrile seizures).
• Participant is taking any medication that is excluded per the protocol.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

199 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participant will receive placebo matching to SPD489 (Lisdexamfetamine dimesylate) capsule for 6 weeks.

Treatment:

Drug: Placebo

SPD489 (Lisdexamfetamine dimesylate)

Experimental group

Description:

Participants will be randomized to receive SPD489 capsule in a 5:5:5:5:6 ratio to SPD489 5, 10, 20, 30 milligram (mg) orally once daily for 6 weeks. Dosing will begin with the lowest strength of SPD489 (5 mg), and will be titrated until the randomly assigned fixed-dose is reached.

Treatment:

Drug: SPD489

Drug: SPD489 (Lisdexamfetamine dimesylate)