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

NCT03260205 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: SPD489-347
• Study Type: interventional
• Target: 199
• Locations: 1 country
• Sites: 48

Brief Summary

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.

Conditions

Attention Deficit Hyperactivity Disorder (ADHD)

Keywords

SPD489; Lisdexamfetamine dimesylate; ADHD; hyperactivity; Neurobehavioral disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6

  ADHD-RS-IV Preschool Version was adapted from the ADHD Rating Scale-IV and provided examples appropriate for the developmental level of preschool children. The ADHD-RS-IV Preschool Version was an 18-item questionnaire that required the respondent to rate the frequency of occurrence of ADHD symptoms as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria. Each item was scored on a 4-point scale ranging from 0 (never or rarely) to 3 (very often) with total scores ranging from 0-54. The 18 items were grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17). Full analysis set (FAS) consisted of all participants in the safety analysis set who had at least 1 post-dose ADHD RS IV preschool version total score assessment.

  Baseline, Week 6

Secondary Outcomes (11)

• Clinical Global Impressions Global Improvement (CGI-I) at Week 6

  Week 6

• Dose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6

  Baseline, Week 6

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From start of study drug administration up to follow-up (Week 7)

• Number of Participants With Potentially Clinically Significant Changes in Vital Signs

  Week 6

• Change From Baseline in Height at Week 6

  Baseline, Week 6

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

SPD489 (Lisdexamfetamine dimesylate)

EXPERIMENTAL

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.

Drug: SPD489 (Lisdexamfetamine dimesylate); Drug: SPD489

Interventions

Placebo DRUG

Placebo matching to SPD489 (Lisdexamfetamine dimesylate) capsule for 6 weeks.

Placebo

SPD489 (Lisdexamfetamine dimesylate) DRUG

SPD489 capsule in a 5:5:5:5:6 ratio to 5, 10, 20, 30 mg orally once daily for 6 weeks.

SPD489 (Lisdexamfetamine dimesylate)

SPD489 DRUG

SPD489

SPD489 (Lisdexamfetamine dimesylate)

Eligibility Criteria

• Age: 4 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (48)

Harmonex, Inc

Dothan, Alabama, 36303, United States

Location

Preferred Research Partners, Inc

Little Rock, Arkansas, 72211, United States

Location

CMB Clinical Trials

Colton, California, 92324, United States

Location

Sun Valley Research Center

Imperial, California, 92251, United States

Location

Alliance for Wellness d/b/a Alliance for Research

Long Beach, California, 90807, United States

Location

Asclepes Research

Panorama City, California, 91402, United States

Location

Psychiatric Centers at San Diego

San Diego, California, 92108, United States

Location

UCSF Dept of Psychiatry

San Francisco, California, 94143, United States

Location

Elite Clinical Trials, Inc

Wildomar, California, 92595, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, 32256, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 32763, United States

Location

Clinical Neuroscience Solutions

Orlando, Florida, 32801, United States

Location

APG Research, LLC

Orlando, Florida, 32803, United States

Location

University of South Florida

St. Petersburg, Florida, 33701, United States

Location

University of South Florida Department Of Psychiatry

Tampa, Florida, 33613, United States

Location

iResearch Atlanta LLC

Decatur, Georgia, 30030, United States

Location

Lake Charles Clinical Trials

Lake Charles, Louisiana, 70629, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Rochester Center for Behavioral Medicine

Rochester Hills, Michigan, 48306, United States

Location

Clinical Neurophysiology Services

Sterling Heights, Michigan, 48314, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Premier Psychiatric Reseach Institute, LLC

Lincoln, Nebraska, 68526, United States

Location

Jersey Shore University Medical Center (JSUMC)

Neptune City, New Jersey, 07753, United States

Location

Manhattan Behavioral Medicine

New York, New York, 10036, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Pediatric Associates of Fairfield, Inc

Fairfield, Ohio, 45014, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73103, United States

Location

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, 73112, United States

Location

Paradigm Research Professionals

Oklahoma City, Oklahoma, 73118, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73120, United States

Location

Cyn3rgy Research Center

Gresham, Oregon, 97030, United States

Location

Rainbow Research Inc

Barnwell, South Carolina, 29812, United States

Location

Carolina Clinical Trials, Inc.

Charleston, South Carolina, 29407, United States

Location

Coastal Carolina Research

Mt. Pleasant, South Carolina, 29464, United States

Location

Clinical Neuroscience Solutions, Inc

Memphis, Tennessee, 38119, United States

Location

BioBehavioral Research of Austin

Austin, Texas, 78759, United States

Location

Bayou City Research Limited

Houston, Texas, 77007, United States

Location

BI Research Center

Houston, Texas, 77084, United States

Location

Red Oak Psychiatry Associates

Houston, Texas, 77090, United States

Location

Road Runner Research

San Antonio, Texas, 78249, United States

Location

Family Psychiatry of the Woodlands

The Woodlands, Texas, 77381, United States

Location

Ericksen Research and Development

Clinton, Utah, 84015, United States

Location

Clinical Research Partners, LLC

Petersburg, Virginia, 23805, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Seattle Childrens Hospital, Pearl Clinic

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Childress AC, Lloyd E, Jacobsen L, Gunawardhana L, Johnson SA Jr, Findling RL. Efficacy and Safety of Lisdexamfetamine in Preschool Children With Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2022 Dec;61(12):1423-1434. doi: 10.1016/j.jaac.2022.03.034. Epub 2022 May 13.

  PMID: 35577034 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Spasm

Interventions

Lisdexamfetamine Dimesylate

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dextroamphetamine; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2017
• First Posted: August 24, 2017
• Study Start: September 6, 2017
• Primary Completion: October 23, 2018
• Study Completion: October 23, 2018
• Last Updated: June 8, 2021
• Results First Posted: January 18, 2020

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (48)