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CompletedNCT03260205Updated Jun 8, 2021Results posted

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

A Phase 3 interventional study of Placebo and SPD489 (Lisdexamfetamine dimesylate) in Attention Deficit Hyperactivity Disorder (ADHD), sponsored by Shire. Completed at 48 sites in United States. Open to participants aged 4 Years to 5 Years. Per ClinicalTrials.gov, last updated 2021-06-08.

Sponsored by Shire · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
199
Allocation
Randomized
Ages
4 Years to 5 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Attention Deficit Hyperactivity Disorder (ADHD)

Keywords

  • SPD489
  • Lisdexamfetamine dimesylate
  • ADHD
  • hyperactivity
  • Neurobehavioral disorder
03

Who can participate

Ages eligible
4 Years to 5 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • Participant is required to or anticipates the need to take any prohibited medications or medications that have central nervous system (CNS) effects or have an effect on performance. Stable use of bronchodilator inhalers is not exclusionary.
  • 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.
  • Participant has a height less than equal to (\<=) 5th percentile for age and sex at the screening visit (Visit -1).
  • Participant has a weight \<= 5th percentile for age and sex at the screening visit (Visit -1).
  • Participant lives with anyone who currently abuses stimulants or cocaine.
  • Participant has a history of seizures (other than infantile febrile seizures).
  • Participant is taking any medication that is excluded per the protocol.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
199 participants (actual)

Study arms

  • Placebo comparator
    Placebo

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

    Drug: Placebo

  • Experimental
    SPD489 (Lisdexamfetamine dimesylate)

    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

  • DrugPlacebo

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

  • DrugSPD489 (Lisdexamfetamine dimesylate)

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

  • DrugSPD489

    SPD489

05

What researchers measure

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.

    Time frame: Baseline, Week 6

Secondary outcomes

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

    CGI-I was an overall assessment of global symptom improvement by evaluation of the participant's condition severity and improvement over time. Scoring was done based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), where higher score reported worse condition. The scoring was elaborated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. 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.

    Time frame: Week 6

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

    Dose response relationship was evaluated by using the ADHD-RS Preschool Version Total Score. 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 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 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). Dose response analysis set consisted of all participants in the safety analysis set who had at least 1 valid primary efficacy measurement on the randomized target dose level of the investigational product.

    Time frame: Baseline, Week 6

  3. 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 investigational product (IP) and that does not necessarily had a causal relationship with this treatment. TEAEs were defined as AEs that start or deteriorate on or after the date of the first dose of IP and no later than 3 days following the last dose of IP.

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

  4. Number of Participants With Potentially Clinically Significant Changes in Vital Signs

    Vital sign assessments included blood pressure (systolic and diastolic), average pulse rate. Number of participants with potentially clinically significant changes in vital signs were reported. mmHg represents millimetre of mercury in the outcome measure data.

    Time frame: Week 6

  5. Change From Baseline in Height at Week 6

    Height was measured in inche without shoes, with the participant stood on a flat surface and with chin parallel to the floor.

    Time frame: Baseline, Week 6

  6. Change From Baseline in Body Weight at Week 6

    Body weight was measured in percentile without shoes. Body weight percentile was normalized by sex and age using the Centers for Disease Control and Prevention (CDC) growth charts. Body weight percentiles were categorized as lesser than (\<) 5th, 5th to \< 95th, and greater than or equal to (\>=) 95th percentiles. Change from baseline in body weight at Week 6 was reported.

    Time frame: Baseline, Week 6

  7. Change From Baseline in Body Mass Index (BMI) at Week 6

    BMI was derived from height and weight. BMI percentile 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). Change from baseline in body mass index at Week 6 was reported.

    Time frame: Baseline, Week 6

  8. Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values

    Clinical laboratory evaluations included biochemistry and endocrinology, hematology, and urinalysis. Number of participants with potentially clinically significant changes in clinical laboratory values were reported. ULN in measure data represents upper limit of normal, mcmol/L represents to Micromoles Per Litre, \> = represents greater than or equal to.

    Time frame: Week 6

  9. Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters

    Number of participants with potentially clinically significant changes in ECG parameters were reported. QTcF interval represents QT Fridericia's Correction Formula interval, QTcB interval represents QTc corrected by Bazett's in measure data.

    Time frame: Week 6

  10. Children's Sleep Habits Questionnaire (CSHQ) at Week 6

    Children's Sleep Habits Questionnaire was a tool designed to screen the most common sleep problems in children, and consisted of 33 items for scoring. The instrument evaluated 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.

    Time frame: Week 6

  11. Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS)

    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.

    Time frame: Up to Week 6

06

Results

Posted Jan 18, 2020

Participant flow

The study was conducted at 49 sites in United States between 06 September 2017 (first participant enrolled) and 23 October 2018 (last participant completed).

Participant flow — Overall Study
MilestonePlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Started4640373739
Received treatment4539353438
Completed3732263025
Not completed9811714
Withdrew: Adverse event20224
Withdrew: Lost to follow-up22115
Withdrew: Protocol violation00201
Withdrew: Withdrawal by participant or parent/lar45102
Withdrew: Other: unspecified00311
Withdrew: Participant who did not received anydose11231

Outcome measures

PrimaryChange 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.

Time frame:
Baseline, Week 6
Reported as:
Mean · Score on a scale
Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6
Score on a scalePlaceboPooled SPD489 Doses (10, 20, and 30 mg)
Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6-9.1 ± 2.36-14.2 ± 1.57
Statistical analysis
  • Placebo vs Pooled SPD489 Doses (10, 20, and 30 mg) · MMRM · p = 0.0242 · Difference in least square mean: -5.9 · 95% CI -11.01 to -0.78
SecondaryClinical Global Impressions Global Improvement (CGI-I) at Week 6

CGI-I was an overall assessment of global symptom improvement by evaluation of the participant's condition severity and improvement over time. Scoring was done based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), where higher score reported worse condition. The scoring was elaborated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. 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.

Time frame:
Week 6
Reported as:
Mean · Score on a scale
Clinical Global Impressions Global Improvement (CGI-I) at Week 6
Score on a scalePlaceboPooled SPD489 Doses (10, 20, and 30 mg)
Clinical Global Impressions Global Improvement (CGI-I) at Week 63.4 ± 0.182.8 ± 0.13
Statistical analysis
  • Placebo vs Pooled SPD489 Doses (10, 20, and 30 mg) · MMRM · p = 0.0074 · Difference in least mean square: -0.6 · 95% CI -1.03 to -0.16
SecondaryDose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6

Dose response relationship was evaluated by using the ADHD-RS Preschool Version Total Score. 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 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 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). Dose response analysis set consisted of all participants in the safety analysis set who had at least 1 valid primary efficacy measurement on the randomized target dose level of the investigational product.

Time frame:
Baseline, Week 6
Reported as:
Mean · Score on a scale
Dose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6
Score on a scalePlaceboSPD489 30 mgSPD489 20 mgSPD489 10 mgSPD489 5 mg
Dose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6-9.1 ± 2.36-15.3 ± 2.62-17.0 ± 2.90-10.8 ± 2.63-13.5 ± 2.53
SecondaryNumber of Participants With Treatment-Emergent Adverse Events (TEAEs)

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

Time frame:
From start of study drug administration up to follow-up (Week 7)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
ParticipantsPlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)1913151822
SecondaryNumber of Participants With Potentially Clinically Significant Changes in Vital Signs

Vital sign assessments included blood pressure (systolic and diastolic), average pulse rate. Number of participants with potentially clinically significant changes in vital signs were reported. mmHg represents millimetre of mercury in the outcome measure data.

Time frame:
Week 6
Reported as:
Count of participants · Participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs
ParticipantsPlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Pulse: >=130 beats per minute (bpm), Week 600000
Pulse: <=55 bpm, Week 600000
Systolic Blood Pressure (BP): >=120 mmHg, Week 600010
Systolic BP: <75 mmHg, Week 600000
Diastolic BP: >=85 mmHg, Week 600000
Diastolic BP: <40 mmHg, Week 600000
SecondaryChange From Baseline in Height at Week 6

Height was measured in inche without shoes, with the participant stood on a flat surface and with chin parallel to the floor.

Time frame:
Baseline, Week 6
Reported as:
Mean · Centimeter
Change From Baseline in Height at Week 6
CentimeterPlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Change From Baseline in Height at Week 60.7 ± 1.210.7 ± 1.500.7 ± 1.081.0 ± 1.290.5 ± 1.20
SecondaryChange From Baseline in Body Weight at Week 6

Body weight was measured in percentile without shoes. Body weight percentile was normalized by sex and age using the Centers for Disease Control and Prevention (CDC) growth charts. Body weight percentiles were categorized as lesser than (\<) 5th, 5th to \< 95th, and greater than or equal to (\>=) 95th percentiles. Change from baseline in body weight at Week 6 was reported.

Time frame:
Baseline, Week 6
Reported as:
Mean · Weight percentile
Change From Baseline in Body Weight at Week 6
Weight percentilePlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Change From Baseline in Body Weight at Week 6-1.1 ± 5.94-1.0 ± 8.00-2.8 ± 6.37-4.8 ± 9.59-5.8 ± 8.05
SecondaryChange From Baseline in Body Mass Index (BMI) at Week 6

BMI was derived from height and weight. BMI percentile 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). Change from baseline in body mass index at Week 6 was reported.

Time frame:
Baseline, Week 6
Reported as:
Mean · BMI percentile
Change From Baseline in Body Mass Index (BMI) at Week 6
BMI percentilePlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Change From Baseline in Body Mass Index (BMI) at Week 6-1.6 ± 11.17-0.9 ± 14.06-5.1 ± 10.49-6.7 ± 14.28-7.4 ± 11.91
SecondaryNumber of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values

Clinical laboratory evaluations included biochemistry and endocrinology, hematology, and urinalysis. Number of participants with potentially clinically significant changes in clinical laboratory values were reported. ULN in measure data represents upper limit of normal, mcmol/L represents to Micromoles Per Litre, \> = represents greater than or equal to.

Time frame:
Week 6
Reported as:
Count of participants · Participants
Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values
ParticipantsPlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Eosinophils/Leukocytes: Greater than (>)10%10250
Lymphocytes/Leukocytes: Greater than (>) 70%10000
Neutrophils/Leukocytes: Less than (<) 30%62131
Platelets: >600x10^9/Litre (L)00001
Alanine aminotransferase: >= 3x ULN10000
Aspartate aminotransferase: >=3x ULN10000
Creatinine: >176.8 mcmol/L or >1.5x ULN00010
Glucose: <3.05 Millimole per liter (mmol/L)11000
Glucose: >8.88 Millimole per liter (mmol/L)00100
Potassium: >5.5 Millimole per liter (mmol/L)10000
Ketones: Positive value (excluding trace)10233
Occult blood: Positive value (excluding trace)10113
Protein: Positive value (excluding trace)71345
SecondaryNumber of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters

Number of participants with potentially clinically significant changes in ECG parameters were reported. QTcF interval represents QT Fridericia's Correction Formula interval, QTcB interval represents QTc corrected by Bazett's in measure data.

Time frame:
Week 6
Reported as:
Count of participants · Participants
Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters
ParticipantsPlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Heart Rate (< 55 Beats per minute)00000
Heart Rate (> 130 Beats per minute)00000
QRS Interval (> = 90 millisecond [msec])11012
QT Interval (> = 440 msec)00000
QTcB Interval (> =440 msec and <480 msec)11232
QTcB Interval (>=480 msec and <500 msec)00000
QTcB Interval (>=500 msec)00000
QTcF Interval (> =440 msec and <480 msec)00000
QTcF Interval (>=480 msec and <500 msec)00000
QTcF Interval (>=500 msec)00000
ECG Abnormality - Rhythm01000
SecondaryChildren's Sleep Habits Questionnaire (CSHQ) at Week 6

Children's Sleep Habits Questionnaire was a tool designed to screen the most common sleep problems in children, and consisted of 33 items for scoring. The instrument evaluated 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.

Time frame:
Week 6
Reported as:
Mean · Score on scale
Children's Sleep Habits Questionnaire (CSHQ) at Week 6
Score on scalePlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Bedtime resistance: Week 69.7 ± 3.229.4 ± 3.3010.3 ± 3.3610.2 ± 3.6010.3 ± 3.30
Sleep-onset delay: Week 61.7 ± 0.741.7 ± 0.801.8 ± 0.751.8 ± 0.751.8 ± 0.76
Sleep duration: Week 63.9 ± 1.203.9 ± 1.203.9 ± 1.354.1 ± 1.704.1 ± 1.62
Sleep anxiety: Week 65.7 ± 2.375.8 ± 2.176.5 ± 2.366.5 ± 2.756.4 ± 2.37
Night wakings: Week 64.7 ± 1.784.2 ± 1.234.6 ± 1.584.3 ± 1.364.1 ± 1.39
Parasomnias: Week 68.6 ± 1.978.9 ± 1.708.8 ± 1.508.2 ± 1.548.4 ± 1.34
Sleep-disordered breathing: Week 63.5 ± 1.003.6 ± 1.023.3 ± 0.683.4 ± 0.703.5 ± 0.95
Daytime sleepiness: Week 610.9 ± 3.5810.9 ± 3.3310.3 ± 3.339.8 ± 3.5712.4 ± 4.46
SecondaryNumber of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS)

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.

Time frame:
Up to Week 6
Reported as:
Number · Participants
Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS)
ParticipantsPlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS)01110

Adverse events

Collected over From start of the study drug administration up to follow up (Week 7). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/45 (0%)0/45 (0%)4/45 (8.9%)
SPD489 5 mg0/39 (0%)0/39 (0%)8/39 (20.5%)
SPD489 10 mg0/35 (0%)0/35 (0%)11/35 (31.4%)
SPD489 20 mg0/34 (0%)0/34 (0%)14/34 (41.2%)
SPD489 30 mg0/38 (0%)0/38 (0%)18/38 (47.4%)
Most frequent other events
Showing 10 of 15
Most frequent other events
EventPlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mg
Decreased appetiteMetabolism and nutrition disorders4/453/393/356/348/38
IrritabilityPsychiatric disorders0/453/394/353/344/38
Affect labilityPsychiatric disorders0/452/393/351/341/38
Initial insomniaPsychiatric disorders2/451/391/350/343/38
ConstipationGastrointestinal disorders1/450/390/352/340/38
NasopharyngitisInfections and infestations0/451/390/352/342/38
Weight decreasedInvestigations0/450/390/352/340/38
HeadacheNervous system disorders0/450/391/352/340/38
CoughRespiratory, thoracic and mediastinal disorders1/451/392/352/342/38
Upper respiratory tract infectionInfections and infestations1/452/392/350/340/38

Baseline characteristics

Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product.

Age, Continuous
Age, Continuous(months)PlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mgTotal
Mean61.9 ± 6.3260.7 ± 6.3260.9 ± 7.1861.1 ± 5.8861.2 ± 7.2361.2 ± 6.54
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mgTotal
Female161213101162
Male2927222427129
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mgTotal
Hispanic or Latino86112532
Not Hispanic or Latino3733243233159
Unknown or Not Reported000000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboSPD489 5 mgSPD489 10 mgSPD489 20 mgSPD489 30 mgTotal
Race — White191718181789
Race — Black or African American232015151689
Race — American Indian or Alaska Native000011
Race — Multiple110136
Race — Other: Not specified112015
Race — Missing100001
07

Study locations

48 sites
  • Harmonex, Inc
    Dothan, Alabama 36303, United States
  • Preferred Research Partners, Inc
    Little Rock, Arkansas 72211, United States
  • CMB Clinical Trials
    Colton, California 92324, United States
  • Sun Valley Research Center
    Imperial, California 92251, United States
  • Alliance for Wellness d/b/a Alliance for Research
    Long Beach, California 90807, United States
  • Asclepes Research
    Panorama City, California 91402, United States
  • Psychiatric Centers at San Diego
    San Diego, California 92108, United States
  • UCSF Dept of Psychiatry
    San Francisco, California 94143, United States
  • Elite Clinical Trials, Inc
    Wildomar, California 92595, United States
  • Avail Clinical Research, LLC
    DeLand, Florida 32720, United States
  • Sarkis Clinical Trials
    Gainesville, Florida 32607, United States
  • Clinical Neuroscience Solutions, Inc.
    Jacksonville, Florida 32256, United States
  • Medical Research Group of Central Florida
    Orange City, Florida 32763, United States
  • Clinical Neuroscience Solutions
    Orlando, Florida 32801, United States
  • APG Research, LLC
    Orlando, Florida 32803, United States
  • University of South Florida
    Saint Petersburg, Florida 33701, United States
  • University of South Florida Department Of Psychiatry
    Tampa, Florida 33613, United States
  • iResearch Atlanta LLC
    Decatur, Georgia 30030, United States
  • Lake Charles Clinical Trials
    Lake Charles, Louisiana 70629, United States
  • Kennedy Krieger Institute
    Baltimore, Maryland 21205, United States
  • Rochester Center for Behavioral Medicine
    Rochester Hills, Michigan 48306, United States
  • Clinical Neurophysiology Services
    Sterling Heights, Michigan 48314, United States
  • Washington University
    Saint Louis, Missouri 63110, United States
  • Premier Psychiatric Reseach Institute, LLC
    Lincoln, Nebraska 68526, United States
  • Jersey Shore University Medical Center (JSUMC)
    Neptune, New Jersey 07753, United States
  • Manhattan Behavioral Medicine
    New York, New York 10036, United States
  • University of Rochester
    Rochester, New York 14642, United States
  • University Hospitals Case Medical Center
    Cleveland, Ohio 44106, United States
  • Pediatric Associates of Fairfield, Inc
    Fairfield, Ohio 45014, United States
  • IPS Research Company
    Oklahoma City, Oklahoma 73103, United States
  • Oklahoma Clinical Research Center
    Oklahoma City, Oklahoma 73112, United States
  • Paradigm Research Professionals
    Oklahoma City, Oklahoma 73118, United States
  • Cutting Edge Research Group
    Oklahoma City, Oklahoma 73120, United States
  • Cyn3rgy Research Center
    Gresham, Oregon 97030, United States
  • Rainbow Research Inc
    Barnwell, South Carolina 29812, United States
  • Carolina Clinical Trials, Inc.
    Charleston, South Carolina 29407, United States
  • Coastal Carolina Research
    Mount Pleasant, South Carolina 29464, United States
  • Clinical Neuroscience Solutions, Inc
    Memphis, Tennessee 38119, United States
  • BioBehavioral Research of Austin
    Austin, Texas 78759, United States
  • Bayou City Research Limited
    Houston, Texas 77007, United States
  • BI Research Center
    Houston, Texas 77084, United States
  • Red Oak Psychiatry Associates
    Houston, Texas 77090, United States
  • Road Runner Research
    San Antonio, Texas 78249, United States
  • Family Psychiatry of the Woodlands
    The Woodlands, Texas 77381, United States
  • Ericksen Research and Development
    Clinton, Utah 84015, United States
  • Clinical Research Partners, LLC
    Petersburg, Virginia 23805, United States
  • Northwest Clinical Research Center
    Bellevue, Washington 98007, United States
  • Seattle Childrens Hospital, Pearl Clinic
    Seattle, Washington 98105, United States
08

References and documents

Publications

  • 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. PubMed 35577034 ↗

Study documents

  • Study protocol · Aug 4, 2017
  • Statistical analysis plan · Jun 7, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT03260205
Lead sponsor
Shire
Responsible party
Sponsor
First posted
Aug 24, 2017
Start date
Sep 6, 2017
Primary completion
Oct 23, 2018
Completion
Oct 23, 2018
Results posted
Jan 18, 2020
Last update
Jun 8, 2021

Study contacts

Study Director
study director · Takeda

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.

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