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

NCT02466386 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: SPD489-348
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 50

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).

Conditions

Attention Deficit Hyperactivity Disorder (ADHD)

Outcome Measures

Primary Outcomes (7)

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

  An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of investigational product.

  From start of study drug administration up to follow-up (Week 53)

• Change From Baseline in Sleep Patterns Assessed by Children's Sleep Habits Questionnaire (CSHQ) at Week 52/ Early Termination (ET)

  Sleep patterns included sleep diary data and children's sleep habits questionnaire (CSHQ), which was parent report questionnaire designed to screen for the most common sleep problems in children, and consisted of 33 items for scoring and several extra items intended to provide administrators with other potentially useful information about respondents. The instrument evaluates the child's sleep based on behavior within 8 different sub scales: bedtime resistance, sleep-onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness. Each item receives a score from 1 (problem occurs rarely) to 3 (problem usually occurs); therefore, a higher score is the worse outcome. Scale ranges are as follows: bedtime resistance: 6 to 18, sleep onset delay: 1 to 3, sleep duration: 3 to 9, sleep anxiety: 4 to 12, night walkings: 3 to 9, parasomnias: 7 to 21, sleep-disordered breathing: 3 to 9, and daytime sleepiness: 8 to 24.

  Week 52/ET

• Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters at Week 52/ Early Termination (ET)

  12-lead ECG was evaluated and recorded. ECG variables included heart rate, PR interval, QRS interval, QT interval, and corrected QT interval (QTc). The QTc was calculated using both Bazett (QTcB=QT/\[RR\]1/2) and Fridericia (QTcF=QT/\[RR\]1/3) corrections. Here, \> = represents "greater than or equal to", \< represents "lesser than" and \> represents "greater than".

  Week 52/ET

• Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS) at Week 52/ Early Termination (ET)

  C-SSRS was semi-structured interview that captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview included definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. The C-SSRS contained 2 required items pertaining to suicidal ideation, 4 required items pertaining to suicidal behavior, and 1 required item pertaining to non-suicidal but self-injurious behavior. In situations where there was a positive response to the screening questions, there were 8 additional suicidal ideation items and 4 additional suicidal behavior items which were completed. Thus, there was a maximum of 19 items to be completed. Here number of participants responded as yes to suicidal ideation or behaviour were reported.

  Week 52/ET

• Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values at Week 52/ Early Termination (ET)

  Clinical laboratory evaluations included biochemistry and endocrinology, hematology, and urinalysis. Number of participants with potentially clinically significant changes in clinical laboratory values were reported.

  Week 52/ET

• Number of Participants With Potentially Clinically Significant Changes in Vital Signs at Week 52/ Early Termination (ET)

  Vital sign assessments included blood pressure, pulse and respiratory rate. Number of participants with potentially clinically significant changes in vital signs were reported.

  Week 52/ET

• Number of Participants With Shift From Baseline in Body Mass Index (BMI) Percentiles at Week 52/Early Termination (ET)

  BMI was derived from height and weight. BMI was normalized by sex and age using the CDC growth charts. BMI percentiles were categorized as: Underweight (BMI \< 5th percentile); Healthy weight (BMI 5th percentile up to \< 85th percentile); Overweight (BMI 85th percentile \< 95th percentile); Obese (BMI \>= 95th percentile). Number of participants with shift from baseline in BMI percentile categories at Week 52/ET was reported.

  Week 52/ET

Secondary Outcomes (2)

• Clinical Global Impressions Global Improvement (CGI-I) at Week 52/ Early Termination (ET)

  Week 52/ET

• Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 52/ Early Termination (ET)

  Week 52/ET

Study Arms (1)

SPD489

EXPERIMENTAL

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.

Drug: SPD489

Interventions

SPD489 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.

Also known as: Lisdexamfetamine dimesylate

SPD489

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.
• Roll-over participant from antecedent SPD489-347 study:
• a. Participant completed the antecedent study (SPD489-347)
• 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
• 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.
• Participant has a Clinical Global Impressions - Severity of Illness (CGI-S) score \>=4 at the Baseline Visit (Visit 0).
• Participant has a Peabody Picture Vocabulary Test, Fourth Edition standard score of \>=70 at the Screening Visit (Visit -1).
• 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.
• 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.
• Participant has lived with the same parent(s) or guardian for \>=6 months.

You may not qualify if:

• 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.
• 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 \>= 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.
• 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.
• Participant is taking any medication that is excluded per the protocol.
• 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.
• 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.
• 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 glaucoma.
• Participant has failed to fully respond, based on investigator judgment, to an adequate course of amphetamine therapy.
• 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:
• post-traumatic stress disorder (PTSD) or adjustment disorder
• bipolar illness, psychosis, or family history of these disorders

Sponsors & Collaborators

• Shire: lead

Study Sites (50)

Harmonex, Inc

Dothan, Alabama, 36303, United States

Location

Preferred Research Partners, Inc.

Little Rock, Arkansas, 72211, 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

AVIDA

Newport Beach, California, 92660, United States

Location

Asclepes Research

Panorama City, California, 91402, United States

Location

Psychiatric Centers at San Diego

San Diego, California, 92108, United States

Location

University of California

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

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

Center For Psychiatry and Behavioral Medicine In

Las Vegas, Nevada, 89128, United States

Location

Jersey Shore University Medical Center (JSUMC)

Neptune City, New Jersey, 7753, United States

Location

Manhattan Behavioral Medicine

New York, New York, 10036, United States

Location

University of Rochester

Rochester, New York, 14627, United States

Location

Duke Child and Family Center

Durham, North Carolina, 27705, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, 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

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• 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.

  PMID: 35230142 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Lisdexamfetamine Dimesylate

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@takeda.com

+1 866 842 5335

Study Officials

• Shire Physician

  Shire

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 9, 2015
• Study Start: August 21, 2015
• Primary Completion: January 3, 2020
• Study Completion: January 3, 2020
• Last Updated: March 5, 2021
• Results First Posted: March 5, 2021

Record last verified: 2021-02

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 (50)