Safety and Tolerability Study of SPD489 in Preschool Children Aged 4-5 Years, Diagnosed With Attention-deficit/Hyperactivity Disorder

NCT ID: NCT02466386

Last Updated: 2021-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 113 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-21
• Study Completion Date: 2020-01-03

Brief Summary

The purpose of this study is to evaluate the long-term safety of SPD489 administered as a daily morning dose (5, 10, 15, 20, and 30 mg/day) in preschool children diagnosed with Attention-deficit/Hyperactivity Disorder (ADHD).

Detailed Description

This study is a long-term, open-label study where participants who participated in an antecedent SPD489 study (SPD489-211 [NCT02402166] or SPD489-347 [NCT03260205]) or through direct enrollment. Participants entering into this study will be classified as either a roll-over participants or a direct-enrolled participants.

Conditions

Attention Deficit Hyperactivity Disorder (ADHD)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SPD489

Participants will receive 5 milligrams (mg) of SPD489 capsule orally once daily in the morning and titrated in a step-wise fashion up to either 10 mg, 15 mg, 20 mg, or 30 mg until an optimal dose was reached within 52 weeks.

Group Type: EXPERIMENTAL

SPD489

Intervention Type: DRUG

Participants will receive 5 mg of SPD489 capsule orally once daily in the morning and titrated in a step-wise fashion up to either 10 mg, 15 mg, 20 mg, or 30 mg until an optimal dose was reached.

Interventions

SPD489

Participants will receive 5 mg of SPD489 capsule orally once daily in the morning and titrated in a step-wise fashion up to either 10 mg, 15 mg, 20 mg, or 30 mg until an optimal dose was reached.

Intervention Type: DRUG

Other Intervention Names

Lisdexamfetamine dimesylate

Eligibility Criteria

Inclusion Criteria

1. Participant is male or female aged 4-5 years inclusive at the time of consent from antecedent studies SPD489-211 or SPD489-347 or at the time of consent if directly enrolled.

2. Before completing any study-related procedures, 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 indicating that the participant is aware of the investigational nature of the study. The participant's parent(s) or LAR should understand that the required procedures and restrictions are being conducted in accordance with the International Council of Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996), any updates or revisions, and applicable federal or local regulations.

3. 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. Specifically, the parent/LAR should be available at approximately 7:00AM (+2 hours) to dispense the dose of investigational product for the duration of the study.

4. Roll-over participant from antecedent SPD489-347 study:

a. Participant completed the antecedent study (SPD489-347)

1. Participant must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) criteria for a primary diagnosis of ADHD (any subtype) based on a detailed psychiatric evaluation conducted by a sponsor-approved clinician

2. Participant has an attention-deficit/hyperactivity disorder rating scale- IV (ADHD-RS-IV) Preschool Version total score at the Baseline Visit (Visit 0) of greater than equals to (>=) 28 for boys and >= 24 for girls.

3. Participant has a Clinical Global Impressions - Severity of Illness (CGI-S) score >=4 at the Baseline Visit (Visit 0).

4. Participant has a Peabody Picture Vocabulary Test, Fourth Edition standard score of >=70 at the Screening Visit (Visit -1).

5. Participant has undergone an adequate course of non-pharmacological treatment based on investigator judgment or the participant has a severe enough condition to consider enrollment without undergoing prior non-pharmacological treatment, based on investigator judgment.

6. Participant has, in the opinion of the investigator, participated in a structured group activity (eg, preschool, sports, Sunday school) so as to assess symptoms and impairment in a setting outside the home.

7. Participant has lived with the same parent(s) or guardian for >=6 months.

Exclusion Criteria

1. Participant was terminated from an antecedent SPD489 study for non-compliance and/or experienced a serious adverse event (SAE) or adverse event (AE) resulting in termination.

2. Participant is required to or anticipates the need to take medications that have central nervous system effects or affect performance, such as, but not limited to, sedating antihistamines and decongestant sympathomimetics, or monoamine oxidase inhibitors. Stable use of bronchodilator inhalers is not exclusionary.

3. Participant has a concurrent chronic or acute illness (such as, but not limited to, severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments conducted in the study or that might increase risk to the participant. Similarly, the participant will be excluded if he or she has any additional condition(s) that, in the investigator's opinion, would prohibit the participant from completing the study or would not be in the best interest of the participant. The additional condition(s) would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol. Mild, stable asthma is not exclusionary.

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

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

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

7. 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 placing them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

8. Participant is taking any medication that is excluded per the protocol.

9. Participant had any clinically significant electrocardiogram (ECG) or clinical laboratory abnormalities at the Screening Visit (Visit -1) or baseline visit (Visit 0), based on investigator judgment.

10. Participant has a history of hyperthyroidism, or current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4) at the Screening Visit (Visit-1) or Visit 0. Treatment with a stable dose of thyroid medication for at least 3 months is permitted.

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

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

13. Participant has glaucoma.

14. Participant has failed to fully respond, based on investigator judgment, to an adequate course of amphetamine therapy.

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

1. post-traumatic stress disorder (PTSD) or adjustment disorder

2. bipolar illness, psychosis, or family history of these disorders

3. pervasive developmental disorder

4. obsessive-compulsive disorder (OCD)

5. psychosis/schizophrenia

6. participant has a serious tic disorder, or a family history of Tourette's disorder

7. 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. Participants with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the investigator

8. a history of physical, sexual, or emotional abuse

9. 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.

16. Participant has initiated behavioral therapy within 1 month of the baseline visit (Visit 0). Participant may not initiate behavioral therapy during the study.

17. Participant has a height <=5th percentile for age and sex at the screening visit (Visit -1).

18. Participant has a weight <=5th percentile for age and sex at the screening visit (Visit -1).

19. Participant lives with anyone who currently abuses stimulants or cocaine.

20. Participant has a history of seizures (other than infantile febrile seizures).

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shire Physician

Role: STUDY_DIRECTOR

Shire

Locations

Harmonex, Inc

Dothan, Alabama, United States

Preferred Research Partners, Inc.

Little Rock, Arkansas, United States

Sun Valley Research Center

Imperial, California, United States

Alliance for Wellness d/b/a Alliance for Research

Long Beach, California, United States

AVIDA

Newport Beach, California, United States

Asclepes Research

Panorama City, California, United States

Psychiatric Centers at San Diego

San Diego, California, United States

University of California

San Francisco, California, United States

Elite Clinical Trials, Inc

Wildomar, California, United States

Avail Clinical Research, LLC

DeLand, Florida, United States

Sarkis Clinical Trials

Gainesville, Florida, United States

Medical Research Group of Central Florida

Orange City, Florida, United States

Clinical Neuroscience Solutions

Orlando, Florida, United States

APG Research, LLC

Orlando, Florida, United States

University of South Florida

St. Petersburg, Florida, United States

University of South Florida Department Of Psychiatry

Tampa, Florida, United States

iResearch Atlanta LLC

Decatur, Georgia, United States

Lake Charles Clinical Trials

Lake Charles, Louisiana, United States

Kennedy Krieger Institute

Baltimore, Maryland, United States

Rochester Center for Behavioral Medicine

Rochester Hills, Michigan, United States

Clinical Neurophysiology Services

Sterling Heights, Michigan, United States

Washington University

St Louis, Missouri, United States

Premier Psychiatric Reseach Institute, LLC

Lincoln, Nebraska, United States

Center For Psychiatry and Behavioral Medicine In

Las Vegas, Nevada, United States

Jersey Shore University Medical Center (JSUMC)

Neptune City, New Jersey, United States

Manhattan Behavioral Medicine

New York, New York, United States

University of Rochester

Rochester, New York, United States

Duke Child and Family Center

Durham, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Pediatric Associates of Fairfield, Inc.

Fairfield, Ohio, United States

IPS Research Company

Oklahoma City, Oklahoma, United States

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, United States

Paradigm Research Professionals

Oklahoma City, Oklahoma, United States

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States

Cyn3rgy Research Center

Gresham, Oregon, United States

Rainbow Research Inc

Barnwell, South Carolina, United States

Carolina Clinical Trials, Inc.

Charleston, South Carolina, United States

Coastal Carolina Research

Mt. Pleasant, South Carolina, United States

Clinical Neuroscience Solutions, Inc

Memphis, Tennessee, United States

BioBehavioral Research of Austin

Austin, Texas, United States

Bayou City Research Limited

Houston, Texas, United States

BI Research Center

Houston, Texas, United States

Red Oak Psychiatry Associates

Houston, Texas, United States

Road Runner Research

San Antonio, Texas, United States

Family Psychiatry of the Woodlands

The Woodlands, Texas, United States

Ericksen Research and Development

Clinton, Utah, United States

Clinical Research Partners, LLC

Petersburg, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

Seattle Childrens Hospital

Seattle, Washington, United States

Countries

United States

References

Childress AC, Lloyd E, Johnson SA Jr, Gunawardhana L, Arnold V. A Long-Term, Open-Label Safety and Tolerability Study of Lisdexamfetamine Dimesylate in Children Aged 4-5 Years with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2022 Mar;32(2):98-106. doi: 10.1089/cap.2021.0138. Epub 2022 Mar 8.

Reference Type: DERIVED

PMID: 35230142 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Protocol

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Study Protocol: Amendment 2

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SPD489-348

Identifier Type: -

Identifier Source: org_study_id