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

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.
 
ClinicalTrials.gov Identifier: NCT03260205
Recruitment Status : Completed
First Posted : August 24, 2017
Results First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Attention Deficit Hyperactivity Disorder (ADHD)
Interventions Drug: Placebo
Drug: SPD489 (Lisdexamfetamine dimesylate)
Drug: SPD489
Enrollment 199
Recruitment Details The study was conducted at 49 sites in United States between 06 September 2017 (first participant enrolled) and 23 October 2018 (last participant completed).
Pre-assignment Details A total of 284 participants were screened of them 85 participants were screen failures and did not receive any treatment. 199 participants (153 participants for SPD489 treatment and 46 participants for placebo treatment) were randomized, out of them 150 participants completed the study.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks. Participants received SPD489 5 mg capsule orally once daily for 6 weeks. Participants received SPD489 10 mg capsule orally once daily for 6 weeks. Participants received SPD489 20 mg capsule orally once daily for 6 weeks. Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Period Title: Overall Study
Started 46 40 37 37 39
Received Treatment 45 39 35 34 38
Completed 37 32 26 30 25
Not Completed 9 8 11 7 14
Reason Not Completed
Adverse Event             2             0             2             2             4
Lost to Follow-up             2             2             1             1             5
Protocol Violation             0             0             2             0             1
Withdrawal by Participant or Parent/LAR             4             5             1             0             2
Other: Unspecified             0             0             3             1             1
Participant Who Did Not Received AnyDose             1             1             2             3             1
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg Total
Hide Arm/Group Description Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks. Participants received SPD489 5 mg capsule orally once daily for 6 weeks. Participants received SPD489 10 mg capsule orally once daily for 6 weeks. Participants received SPD489 20 mg capsule orally once daily for 6 weeks. Participants received SPD489 30 mg capsule orally once daily for 6 weeks. Total of all reporting groups
Overall Number of Baseline Participants 45 39 35 34 38 191
Hide Baseline Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 45 participants 39 participants 35 participants 34 participants 38 participants 191 participants
61.9  (6.32) 60.7  (6.32) 60.9  (7.18) 61.1  (5.88) 61.2  (7.23) 61.2  (6.54)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 39 participants 35 participants 34 participants 38 participants 191 participants
Female
16
  35.6%
12
  30.8%
13
  37.1%
10
  29.4%
11
  28.9%
62
  32.5%
Male
29
  64.4%
27
  69.2%
22
  62.9%
24
  70.6%
27
  71.1%
129
  67.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 39 participants 35 participants 34 participants 38 participants 191 participants
Hispanic or Latino
8
  17.8%
6
  15.4%
11
  31.4%
2
   5.9%
5
  13.2%
32
  16.8%
Not Hispanic or Latino
37
  82.2%
33
  84.6%
24
  68.6%
32
  94.1%
33
  86.8%
159
  83.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 45 participants 39 participants 35 participants 34 participants 38 participants 191 participants
White
19
  42.2%
17
  43.6%
18
  51.4%
18
  52.9%
17
  44.7%
89
  46.6%
Black or African American
23
  51.1%
20
  51.3%
15
  42.9%
15
  44.1%
16
  42.1%
89
  46.6%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.6%
1
   0.5%
Multiple
1
   2.2%
1
   2.6%
0
   0.0%
1
   2.9%
3
   7.9%
6
   3.1%
Other: Not specified
1
   2.2%
1
   2.6%
2
   5.7%
0
   0.0%
1
   2.6%
5
   2.6%
Missing
1
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.5%
1.Primary Outcome
Title Change From Baseline in Clinician-Administered Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version Total Score at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. This outcome was pre-specified to collect and analyze pooled groups of SPD489 doses. The data were planned, analyzed, and reported only for the placebo and the pooled 10, 20, 30 mg doses of SPD489 arms.
Arm/Group Title Placebo Pooled SPD489 Doses (10, 20, and 30 mg)
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.
Overall Number of Participants Analyzed 37 84
Mean (Standard Error)
Unit of Measure: Score on a scale
-9.1  (2.36) -14.2  (1.57)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pooled SPD489 Doses (10, 20, and 30 mg)
Comments This outcome measure was analyzed using the linear mixed-effects model for repeated measures (MMRM). From a MMRM analysis over all post-baseline visits, with the change from baseline in ADHD-RS-IV preschool version total score as the outcome, treatment, visit, and treatment-by-visit interaction as fixed effect, baseline ADHD-RS-IV and baseline ADHD-RS-IV score-by-visit interaction as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0242
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Square Mean
Estimated Value -5.9
Confidence Interval (2-Sided) 95%
-11.01 to -0.78
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Clinical Global Impressions Global Improvement (CGI-I) at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. This outcome was pre-specified to collect and analyze pooled groups of SPD489 doses. The data were planned, analyzed, and reported only for the placebo and the pooled 10, 20, 30 mg doses of SPD489 arms.
Arm/Group Title Placebo Pooled SPD489 Doses (10, 20, and 30 mg)
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 10, 20, and 30 mg capsule orally once daily for 6 weeks were pooled.
Overall Number of Participants Analyzed 37 84
Mean (Standard Error)
Unit of Measure: Score on a scale
3.4  (0.18) 2.8  (0.13)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Pooled SPD489 Doses (10, 20, and 30 mg)
Comments This outcome measure was analyzed using the linear mixed-effects model for repeated measures (MMRM). From a MMRM analysis over all post-baseline Visits, with the CGI-I score as the outcome, treatment, visit, and treatment-by-visit interaction as fixed effect, baseline CGI-S as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Mean Square
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.03 to -0.16
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Dose Response Relationship for Change From Baseline in ADHD-RS-IV Preschool Version Total Score in Preschool Children at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Dose response analysis set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Each SPD489 arm is compared with placebo sequentially, with the highest dose level first.
Arm/Group Title Placebo SPD489 30 mg SPD489 20 mg SPD489 10 mg SPD489 5 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received fixed dose of SPD489 30 mg capsule orally once daily for 6 weeks.
Participants received fixed dose of SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received fixed dose of SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received fixed dose of SPD489 5 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 37 26 30 26 33
Mean (Standard Error)
Unit of Measure: Score on a scale
-9.1  (2.36) -15.3  (2.62) -17.0  (2.90) -10.8  (2.63) -13.5  (2.53)
4.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 45 39 35 34 38
Measure Type: Count of Participants
Unit of Measure: Participants
19
  42.2%
13
  33.3%
15
  42.9%
18
  52.9%
22
  57.9%
5.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Changes in Vital Signs
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 41 34 32 33 32
Measure Type: Count of Participants
Unit of Measure: Participants
Pulse: >=130 beats per minute (bpm), Week 6
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Pulse: <=55 bpm, Week 6
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Systolic Blood Pressure (BP): >=120 mmHg, Week 6
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.0%
0
   0.0%
Systolic BP: <75 mmHg, Week 6
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Diastolic BP: >=85 mmHg, Week 6
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Diastolic BP: <40 mmHg, Week 6
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Change From Baseline in Height at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 41 34 32 33 32
Mean (Standard Deviation)
Unit of Measure: Centimeter
0.7  (1.21) 0.7  (1.50) 0.7  (1.08) 1.0  (1.29) 0.5  (1.20)
7.Secondary Outcome
Title Change From Baseline in Body Weight at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 41 34 32 33 32
Mean (Standard Deviation)
Unit of Measure: Weight percentile
-1.1  (5.94) -1.0  (8.00) -2.8  (6.37) -4.8  (9.59) -5.8  (8.05)
8.Secondary Outcome
Title Change From Baseline in Body Mass Index (BMI) at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 41 34 32 33 32
Mean (Standard Deviation)
Unit of Measure: BMI percentile
-1.6  (11.17) -0.9  (14.06) -5.1  (10.49) -6.7  (14.28) -7.4  (11.91)
9.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Changes in Clinical Laboratory Values
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure and at the specific categories.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 38 33 31 30 28
Measure Type: Count of Participants
Unit of Measure: Participants
Eosinophils/Leukocytes: Greater than (>)10% Number Analyzed 37 participants 30 participants 31 participants 27 participants 28 participants
1
   2.7%
0
   0.0%
2
   6.5%
5
  18.5%
0
   0.0%
Lymphocytes/Leukocytes: Greater than (>) 70% Number Analyzed 37 participants 30 participants 31 participants 27 participants 28 participants
1
   2.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Neutrophils/Leukocytes: Less than (<) 30% Number Analyzed 37 participants 30 participants 31 participants 27 participants 28 participants
6
  16.2%
2
   6.7%
1
   3.2%
3
  11.1%
1
   3.6%
Platelets: >600x10^9/Litre (L) Number Analyzed 36 participants 30 participants 30 participants 25 participants 27 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
Alanine aminotransferase: >= 3x ULN Number Analyzed 38 participants 33 participants 31 participants 26 participants 28 participants
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Aspartate aminotransferase: >=3x ULN Number Analyzed 38 participants 33 participants 31 participants 26 participants 28 participants
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Creatinine: >176.8 mcmol/L or >1.5x ULN Number Analyzed 38 participants 33 participants 31 participants 26 participants 28 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
Glucose: <3.05 Millimole per liter (mmol/L) Number Analyzed 38 participants 33 participants 31 participants 26 participants 28 participants
1
   2.6%
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glucose: >8.88 Millimole per liter (mmol/L) Number Analyzed 38 participants 33 participants 31 participants 26 participants 28 participants
0
   0.0%
0
   0.0%
1
   3.2%
0
   0.0%
0
   0.0%
Potassium: >5.5 Millimole per liter (mmol/L) Number Analyzed 38 participants 33 participants 31 participants 26 participants 28 participants
1
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ketones: Positive value (excluding trace) Number Analyzed 37 participants 33 participants 31 participants 30 participants 27 participants
1
   2.7%
0
   0.0%
2
   6.5%
3
  10.0%
3
  11.1%
Occult blood: Positive value (excluding trace) Number Analyzed 37 participants 33 participants 31 participants 30 participants 27 participants
1
   2.7%
0
   0.0%
1
   3.2%
1
   3.3%
3
  11.1%
Protein: Positive value (excluding trace) Number Analyzed 37 participants 33 participants 31 participants 30 participants 27 participants
7
  18.9%
1
   3.0%
3
   9.7%
4
  13.3%
5
  18.5%
10.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure and at the specific categories.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 41 34 31 32 32
Measure Type: Count of Participants
Unit of Measure: Participants
Heart Rate (< 55 Beats per minute) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Heart Rate (> 130 Beats per minute) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QRS Interval (> = 90 millisecond [msec]) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
1
   2.4%
1
   2.9%
0
   0.0%
1
   3.1%
2
   6.3%
QT Interval (> = 440 msec) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTcB Interval (> =440 msec and <480 msec) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
1
   2.4%
1
   2.9%
2
   6.5%
3
   9.4%
2
   6.3%
QTcB Interval (>=480 msec and <500 msec) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTcB Interval (>=500 msec) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTcF Interval (> =440 msec and <480 msec) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTcF Interval (>=480 msec and <500 msec) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
QTcF Interval (>=500 msec) Number Analyzed 41 participants 34 participants 31 participants 32 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
ECG Abnormality - Rhythm Number Analyzed 4 participants 4 participants 3 participants 3 participants 4 participants
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
11.Secondary Outcome
Title Children's Sleep Habits Questionnaire (CSHQ) at Week 6
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 45 39 35 34 38
Mean (Standard Deviation)
Unit of Measure: Score on scale
Bedtime resistance: Week 6 Number Analyzed 41 participants 34 participants 32 participants 33 participants 32 participants
9.7  (3.22) 9.4  (3.30) 10.3  (3.36) 10.2  (3.60) 10.3  (3.30)
Sleep-onset delay: Week 6 Number Analyzed 41 participants 34 participants 32 participants 33 participants 32 participants
1.7  (0.74) 1.7  (0.80) 1.8  (0.75) 1.8  (0.75) 1.8  (0.76)
Sleep duration: Week 6 Number Analyzed 41 participants 34 participants 32 participants 33 participants 32 participants
3.9  (1.20) 3.9  (1.20) 3.9  (1.35) 4.1  (1.70) 4.1  (1.62)
Sleep anxiety: Week 6 Number Analyzed 41 participants 34 participants 32 participants 31 participants 31 participants
5.7  (2.37) 5.8  (2.17) 6.5  (2.36) 6.5  (2.75) 6.4  (2.37)
Night wakings: Week 6 Number Analyzed 40 participants 34 participants 32 participants 33 participants 32 participants
4.7  (1.78) 4.2  (1.23) 4.6  (1.58) 4.3  (1.36) 4.1  (1.39)
Parasomnias: Week 6 Number Analyzed 41 participants 34 participants 32 participants 33 participants 32 participants
8.6  (1.97) 8.9  (1.70) 8.8  (1.50) 8.2  (1.54) 8.4  (1.34)
Sleep-disordered breathing: Week 6 Number Analyzed 41 participants 34 participants 32 participants 33 participants 32 participants
3.5  (1.00) 3.6  (1.02) 3.3  (0.68) 3.4  (0.70) 3.5  (0.95)
Daytime sleepiness: Week 6 Number Analyzed 41 participants 34 participants 32 participants 33 participants 32 participants
10.9  (3.58) 10.9  (3.33) 10.3  (3.33) 9.8  (3.57) 12.4  (4.46)
12.Secondary Outcome
Title Number of Participants With a Positive Response Using Columbia Suicide Severity Rating Scale (C-SSRS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all randomized set who had taken at least 1 dose of investigational product. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description:
Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks.
Participants received SPD489 5 mg capsule orally once daily for 6 weeks.
Participants received SPD489 10 mg capsule orally once daily for 6 weeks.
Participants received SPD489 20 mg capsule orally once daily for 6 weeks.
Participants received SPD489 30 mg capsule orally once daily for 6 weeks.
Overall Number of Participants Analyzed 45 39 34 34 38
Measure Type: Number
Unit of Measure: Participants
0 1 1 1 0
Time Frame From start of the study drug administration up to follow up (Week 7)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Hide Arm/Group Description Participants received placebo matched to SPD489 capsule orally once daily for 6 weeks. Participants received SPD489 capsule orally at a dose of 5 milligram (mg) once daily for 6 weeks. Participants received SPD489 capsule orally at a dose of 10 mg once daily for 6 weeks. Participants received SPD489 capsule orally at a dose of 20 mg once daily for 6 weeks. Participants received SPD489 capsule orally at a dose of 30 mg once daily for 6 weeks.
All-Cause Mortality
Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/45 (0.00%)      0/39 (0.00%)      0/35 (0.00%)      0/34 (0.00%)      0/38 (0.00%)    
Hide Serious Adverse Events
Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/45 (0.00%)      0/39 (0.00%)      0/35 (0.00%)      0/34 (0.00%)      0/38 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo SPD489 5 mg SPD489 10 mg SPD489 20 mg SPD489 30 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/45 (8.89%)      8/39 (20.51%)      11/35 (31.43%)      14/34 (41.18%)      18/38 (47.37%)    
Gastrointestinal disorders           
Constipation * 1  1/45 (2.22%)  1 0/39 (0.00%)  0 0/35 (0.00%)  0 2/34 (5.88%)  2 0/38 (0.00%)  0
Dry mouth * 1  0/45 (0.00%)  0 2/39 (5.13%)  2 0/35 (0.00%)  0 0/34 (0.00%)  0 0/38 (0.00%)  0
Infections and infestations           
Nasopharyngitis * 1  0/45 (0.00%)  0 1/39 (2.56%)  1 0/35 (0.00%)  0 2/34 (5.88%)  2 2/38 (5.26%)  2
Upper respiratory tract infection * 1  1/45 (2.22%)  1 2/39 (5.13%)  3 2/35 (5.71%)  2 0/34 (0.00%)  0 0/38 (0.00%)  0
Investigations           
Weight decreased * 1  0/45 (0.00%)  0 0/39 (0.00%)  0 0/35 (0.00%)  0 2/34 (5.88%)  2 0/38 (0.00%)  0
Metabolism and nutrition disorders           
Decreased appetite * 1  4/45 (8.89%)  4 3/39 (7.69%)  3 3/35 (8.57%)  3 6/34 (17.65%)  6 8/38 (21.05%)  8
Nervous system disorders           
Headache * 1  0/45 (0.00%)  0 0/39 (0.00%)  0 1/35 (2.86%)  1 2/34 (5.88%)  2 0/38 (0.00%)  0
Somnolence * 1  2/45 (4.44%)  2 0/39 (0.00%)  0 0/35 (0.00%)  0 0/34 (0.00%)  0 2/38 (5.26%)  2
Psychiatric disorders           
Affect lability * 1  0/45 (0.00%)  0 2/39 (5.13%)  2 3/35 (8.57%)  4 1/34 (2.94%)  1 1/38 (2.63%)  1
Aggression * 1  0/45 (0.00%)  0 2/39 (5.13%)  2 0/35 (0.00%)  0 1/34 (2.94%)  1 0/38 (0.00%)  0
Initial insomnia * 1  2/45 (4.44%)  2 1/39 (2.56%)  1 1/35 (2.86%)  1 0/34 (0.00%)  0 3/38 (7.89%)  3
Insomnia * 1  1/45 (2.22%)  1 0/39 (0.00%)  0 1/35 (2.86%)  1 0/34 (0.00%)  0 2/38 (5.26%)  2
Irritability * 1  0/45 (0.00%)  0 3/39 (7.69%)  3 4/35 (11.43%)  4 3/34 (8.82%)  3 4/38 (10.53%)  4
Middle insomnia * 1  0/45 (0.00%)  0 0/39 (0.00%)  0 0/35 (0.00%)  0 0/34 (0.00%)  0 2/38 (5.26%)  2
Respiratory, thoracic and mediastinal disorders           
Cough * 1  1/45 (2.22%)  1 1/39 (2.56%)  1 2/35 (5.71%)  2 2/34 (5.88%)  2 2/38 (5.26%)  2
1
Term from vocabulary, MedDRA 18.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Shire
Phone: 1 866-842-5335
EMail: ClinicalTransparency@shire.com
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03260205    
Other Study ID Numbers: SPD489-347
First Submitted: August 9, 2017
First Posted: August 24, 2017
Results First Submitted: October 22, 2019
Results First Posted: January 18, 2020
Last Update Posted: January 18, 2020