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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02466386
Recruitment Status : Active, not recruiting
First Posted : June 9, 2015
Last Update Posted : January 16, 2019
Information provided by (Responsible Party):

Brief Summary:
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). Participants will be enrolled into this study from antecedent study SPD489-211 (NCT02402166) or SPD489-347 (NCT03260205) (roll-over participants) or through direct enrollment (direct enrolled pariticpants).

Condition or disease Intervention/treatment Phase
Attention Deficit Hyperactivity Disorder (ADHD) Drug: SPD489 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 115 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Open-label, Multicenter, 12-Month Safety and Tolerability Study of SPD489 in Preschool Children Aged 4-5 Years Diagnosed With Attention-deficit / Hyperactivity Disorder
Actual Study Start Date : August 21, 2015
Estimated Primary Completion Date : January 3, 2020
Estimated Study Completion Date : January 3, 2020

Arm Intervention/treatment
Experimental: Roll-over Participants
Participants who has completed the antecedent study (SPD489-211 or SPD489-347) will be included in this arm. Participants will begin with once daily oral dosing of 5 mg of SPD489 and should be titrated in a step wise fashion until an optimal dose is reached with 10, 15, 20, and 30 mg capsules.
Drug: SPD489
SPD489 will be provided orally in 5, 10, 15, 20, and 30 milligram (mg) strength capsules once daily. Participants will be instructed to start with 5 mg of SPD489 and should be titrated in a step wise fashion until an optimal dose is reached with 10, 15, 20, and 30 mg dose.
Other Name: Lisdexamfetamine dimesylate

Experimental: Directly Enrolled Participants
Participant will be directly enrolled in this study and did not participate in antecedent study SPD489-211 or SPD489-347. Participants will begin with once daily oral dosing of 5 mg of SPD489 and should be titrated in a step wise fashion until an optimal dose is reached with 10, 15, 20, and 30 mg capsules.
Drug: SPD489
SPD489 will be provided orally in 5, 10, 15, 20, and 30 milligram (mg) strength capsules once daily. Participants will be instructed to start with 5 mg of SPD489 and should be titrated in a step wise fashion until an optimal dose is reached with 10, 15, 20, and 30 mg dose.
Other Name: Lisdexamfetamine dimesylate

Primary Outcome Measures :
  1. Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline to Week 53 ]
    An adverse event (AE) is 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.

  2. Change From Baseline in Sleep Patterns Assessed by Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: Baseline to Week 52 ]
    Sleep patterns will include sleep diary data and children's sleep habits questionnaire (CSHQ), which is a parent report questionnaire designed to screen for the most common sleep problems in children, and consists 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.

  3. Change From Baseline in Electrocardiogram (ECG) Results [ Time Frame: Baseline to Week 52 ]
    12-lead ECG will be recorded and measured.

  4. Change From Baseline in Suicide Related Behavior Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline to Week 52 ]
    C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. The C-SSRS contains 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 is a positive response to the screening questions, there are 8 additional suicidal ideation items and 4 additional suicidal behavior items which are completed. Thus, there is a maximum of 19 items to be completed.

  5. Change From Baseline in Clinical Laboratory Result [ Time Frame: Baseline to Week 52 ]
    Clinical laboratory analysis include biochemistry, endocrinology, hematology and urinalysis.

  6. Change From Baseline in Vital Signs [ Time Frame: Baseline to Week 52 ]
    Vital sign assessments will include blood pressure, pulse and respiratory rate.

Secondary Outcome Measures :
  1. Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) [ Time Frame: Week 1 to Week 52 ]
    CGI-I provides an overall assessment of global symptom improvement. It is a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

  2. Change From Baseline in Clinician-administered Attention Deficit / Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Preschool Version Total Score [ Time Frame: Baseline to Week 52 ]
    ADHD-RS-IV Preschool Version was adapted from the ADHD Rating Scale-IV and provides examples appropriate for the developmental level of preschool children. The ADHD-RS-IV Preschool Version is an 18-item questionnaire that requires 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 is 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 may be grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17).

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

  5. Direct enrolled participants must meet antecedent study inclusion criteria, as listed below

    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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02466386

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Sponsors and Collaborators
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Study Director: Shire Physician Shire

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Responsible Party: Shire Identifier: NCT02466386     History of Changes
Other Study ID Numbers: SPD489-348
First Posted: June 9, 2015    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lisdexamfetamine Dimesylate
Attention Deficit Disorder with Hyperactivity
Pathologic Processes
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Mental Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents