Safety, Tolerability, Pharmacokinetic, and Efficacy Study of SPD489 in Preschool Children With Attention-deficit/Hyperactivity Disorder

NCT02402166 | Completed Phase 2 Results DMC

• 1 other identifier: SPD489-211
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to gain initial safety, tolerability, pharmacokinetic, and efficacy information on SPD489 in preschool children 4-5 years old who are diagnosed with ADHD. Generating such data will provide data on the use of SPD489 in the preschool ADHD population.

Conditions

Attention Deficit Hyperactivity Disorder (ADHD)

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) at the Specified Dose Level

  An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment-emergent if it had a start date on or after, or had a start date before but increased in severity after the first dose of investigational product.

  From start of study treatment up to safety follow-up (Week 9)

• Change in Sleep Patterns Assessed by Children's Sleep Habits Questionnaire at Week 8 / End of Treatment (ET)

  Children's Sleep Habits Questionnaire is a tool designed to screen the most common sleep problems in children, and consists of 33 items for scoring. The instrument evaluates the child's sleep based on behavior within 8 different subscales: bedtime resistance, sleep-onset delay, sleep duration, sleep anxiety, night walkings, 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, daytime sleepiness: 8 to 24, and total disturbance (items from all scales): 33 to 99.

  Baseline, Week 8/ET

• Number of Participants With Suicide Related Behavior Assessed by Columbia-Suicide Severity Rating Scale Questionnaire (C-SSRS)

  The C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was "yes," the clinician asked questions 3-5. Active suicidal ideation included any participant who answered "yes" to questions 2-5. If the answers to ideation questions 1 and 2 were "No," then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.

  Baseline, Week 8/ET

Secondary Outcomes (3)

• Change From Baseline in Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Preschool Version Total Score at FoTA (Final on Treatment Assessment)

  Baseline, FoTA

• Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I)

  FoTA

• Area Under the Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC 0-last) of SPD489 in Plasma

  Visit 7 [Dose Maintenance Phase] at pre-dose, and 1, 2, 3, 4, 6, and 8 h post-dose

Study Arms (1)

Single Arm

EXPERIMENTAL

There are 4 periods in this study: 1)screening and washout; 2) Dose Optimization; 3) Dose Maintenance; 4) Safety Follow-up. SPD489 will be used to treat all subjects.

Drug: SPD489

Interventions

SPD489 DRUG

All subjects will begin with 5mg of SPD489 daily and will be titrated until optimal dose is reached (5, 10, 15, 20, and 30mg)

Also known as: Lisdexmfetamine dimesylate

Single Arm

Eligibility Criteria

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

You may qualify if:

• Subject is a male or female aged 4-5 years inclusive at the time of consent. Only recruiting male subjects as of December 2015
• Subject's parent or LAR must provide signature of informed consent, and there must be documentation of assent (if applicable) by the subject in accordance with the ICH GCP Guideline E6 (1996) and applicable regulations, before completing any study-related procedures.
• Subject and parent/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 same parent/LAR should be available daily to dispense the dose of investigational product for the study duration.
• Subject must meet DSM-IV-TR criteria for a primary diagnosis of ADHD (all subtypes) based on a detailed psychiatric evaluation conducted by a sponsor-approved clinician
• Subject has an ADHD-RS-IV Preschool Version total score ≥93rd percentile at the Baseline Visit (Visit 0). For boys, this is a score of ≥32. For girls, this is a score of ≥24.
• Subject has a CGI-S score ≥4 at the Baseline Visit (Visit 0).
• Subject has a Peabody Picture Vocabulary Test, Fourth Edition standard score of ≥70 at the Screening Visit (Visit -1).
• Subject has undergone an adequate course of non-pharmacological treatment based on investigator judgment or the subject has a severe enough condition to consider enrollment without undergoing prior non-pharmacological treatment based on investigator judgment.
• Subject has, in the opinion of the investigator, 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.
• Subject has lived with the same parent/LAR for ≥6 months.

You may not qualify if:

• Subject has taken another investigational product or has taken part in a clinical study within 30 days prior to the Screening Visit (Visit -1).
• Subject is well controlled on his/her current ADHD medication with acceptable tolerability.
• Subject has failed to fully respond, based on investigator judgment, to a previously administered adequate course of amphetamine therapy.
• Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
• Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
• Subject has a blood pressure measurement ≥95th percentile for age, sex, and height at the Screening Visit (Visit -1) or the Baseline Visit (Visit 0).
• Subject has a known history of symptomatic cardiovascular disease, 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.
• Subject has any clinically significant electrocardiogram at the Screening Visit (Visit -1) or the Baseline Visit (Visit 0) or clinically significant laboratory abnormalities at the Screening Visit (Visit -1) based on investigator judgment.
• Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone and thyroxine at the Screening Visit (Visit -1). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
• Subject has a current diagnosis of adjustment disorder, autism, psychosis, or bipolar disorder.
• Subject is currently considered at risk for suicide in the opinion of the investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded, based on the assessment of the investigator.
• Subject has a height ≤5th percentile for age and sex at the Screening Visit (Visit -1).
• Subject has a weight ≤5th percentile for age and sex at the Screening Visit (Visit -1).
• Subject has a history of seizures (other than infantile febrile seizures) or a current diagnosis of Tourette's disorder.
• Subject is taking any medication that is excluded.

Sponsors & Collaborators

• Shire: lead

Study Sites (6)

AVIDA

Newport Beach, California, 92660, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Center For Psychiatry and Behavioral Medicine In

Las Vegas, Nevada, 89128, United States

Location

Duke Child and Family Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Houston Clinical Trials, LLC

Houston, Texas, 77098, United States

Location

Related Publications (1)

• Childress AC, Findling RL, Wu J, Kollins SH, Wang Y, Martin P, Robertson B. Lisdexamfetamine Dimesylate for Preschool Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2020 Apr;30(3):128-136. doi: 10.1089/cap.2019.0117. Epub 2020 Feb 11.

  PMID: 32233956 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

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

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2015
• First Posted: March 30, 2015
• Study Start: April 15, 2015
• Primary Completion: June 30, 2016
• Study Completion: June 30, 2016
• Last Updated: June 8, 2021
• Results First Posted: October 25, 2018

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 (6)