Attention Deficit Disorder With Hyperactivity
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of administering SPD503 (Guanfacine hydrochloride) with psychostimulants (amphetamine or methylphenidate) for treatment of ADHD in children and adolescents aged 6-17
Interventions
DRUGMethylphenidate + SPD503 (Guanfacine hydrochloride)
DRUGAmphetamine + SPD503
Sponsors
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with a primary diagnosis of ADHD * Subject on a stable dose of a psychostimulant approved for the treatment of ADHD for at least 1 month, with sub-optimal control in the Investigator's opinion * Male or non-pregnant female subject who agrees to comply with any applicable contraceptive requirements
Exclusion criteria
* Subject has current uncontrolled comorbid psychiatric diagnosis (except ODD and mild anxiety) with significant symptoms * History of seizure during the last 2 years * Subject has any specific cardiac condition or family history of significant cardiac condition * Subject is pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at 6 Weeks | Baseline and 6 weeks | Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 6 weeks | Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. |
| Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Total Score at 6 Weeks | Baseline and 6 weeks | The Conner's Parent Rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) to 3 (very much true) with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior. |
| Number of Participants With Improvement on Parent Global Assessment (PGA) Scores | 6 weeks | Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The PGA is designed to capture parent's opinions of their child's disease (ADHD) severity and improvement. Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. |
| Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks | Baseline and 6 weeks | The Child Health Questionnaire-Parent Form (CHQ-PF50) was developed to measure the physical and psychosocial well-being of children aged 5 years of age and older. Total scoring ranges from 0-100 for each. Increases in scores represent improved well-being in subjects as assessed by their parents. |
Participant flow
Pre-assignment details
Dose titration of SPD503 (Guanfacine HCl) for 3 weeks starting at 1 mg/day and increased in 1 mg weekly increments up to 4 mg/day (or to the highest tolerated dose); then dose maintenance for 3 weeks; then downward titration of SPD503 at 1 mg weekly decrements for 3 weeks while maintaining the subject's current psychostimulant dose and frequency.
Participants by arm
| Arm | Count |
|---|---|
| Methylphenidate + SPD503 Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Methylphenidate was dosed according to the prescribing physician's instructions. | 42 |
| Amphetamine + SPD503 Each group received SPD503 (Guanfacine hydrochloride) at doses up to 4 mg/day coadministered with the psychostimulant. Amphetamine was dosed according to the prescribing physician's instructions. | 33 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Sponsor's decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Amphetamine + SPD503 | Methylphenidate + SPD503 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 33 Participants | 42 Participants | 75 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 11.6 years STANDARD_DEVIATION 2.62 | 11.1 years STANDARD_DEVIATION 1.79 | 11.4 years STANDARD_DEVIATION 2.19 |
| Region of Enrollment United States | 33 Participants | 42 Participants | 75 Participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 20 Participants |
| Sex: Female, Male Male | 26 Participants | 29 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 42 | 29 / 33 |
| serious Total, serious adverse events | 0 / 42 | 0 / 33 |
Outcome results
Primary
Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at 6 Weeks
Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set (FAS) defined as all subjects with a baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate + SPD503 | Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at 6 Weeks | -17.8 Units on a Scale | Standard Deviation 10.2 |
| Amphetamine + SPD503 | Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Total Score at 6 Weeks | -13.8 Units on a Scale | Standard Deviation 11.19 |
Comparison: Change from baseline in ADHD-RS-IV total scorep-value: <0.0001t-test, 2 sided
Comparison: Change from baseline in ADHD-RS-IV total scorep-value: <0.0001t-test, 2 sided
Secondary
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks
The Child Health Questionnaire-Parent Form (CHQ-PF50) was developed to measure the physical and psychosocial well-being of children aged 5 years of age and older. Total scoring ranges from 0-100 for each. Increases in scores represent improved well-being in subjects as assessed by their parents.
Time frame: Baseline and 6 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate + SPD503 | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks | Physical Summary Score | -0.38 Units on a scale | Standard Deviation 5.83 |
| Methylphenidate + SPD503 | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks | Psychosocial Summary Score | 8.98 Units on a scale | Standard Deviation 6.69 |
| Amphetamine + SPD503 | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks | Physical Summary Score | 0.22 Units on a scale | Standard Deviation 11.94 |
| Amphetamine + SPD503 | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Scores at 6 Weeks | Psychosocial Summary Score | 11.56 Units on a scale | Standard Deviation 10 |
Comparison: Change in physical summary scorep-value: 0.7004t-test, 2 sided
Comparison: Change in psychosocial summary scorep-value: <0.0001t-test, 2 sided
Comparison: Change in physical summary scorep-value: 0.9257t-test, 2 sided
Comparison: Change in psychosocial summary scorep-value: <0.0001t-test, 2 sided
Secondary
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Total Score at 6 Weeks
The Conner's Parent Rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) to 3 (very much true) with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior.
Time frame: Baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate + SPD503 | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Total Score at 6 Weeks | -22.18 Units on a Scale | Standard Deviation 15.47 |
| Amphetamine + SPD503 | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Total Score at 6 Weeks | -16.28 Units on a Scale | Standard Deviation 18.12 |
Comparison: Change from baseline in CPRS-R total scorep-value: <0.0001t-test, 2 sided
Comparison: Change from baseline in CPRS-R total scorep-value: 0.0002t-test, 2 sided
Secondary
Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores
Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time frame: 6 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methylphenidate + SPD503 | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 28 Participants |
| Amphetamine + SPD503 | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 18 Participants |
Secondary
Number of Participants With Improvement on Parent Global Assessment (PGA) Scores
Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The PGA is designed to capture parent's opinions of their child's disease (ADHD) severity and improvement. Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time frame: 6 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methylphenidate + SPD503 | Number of Participants With Improvement on Parent Global Assessment (PGA) Scores | 32 Participants |
| Amphetamine + SPD503 | Number of Participants With Improvement on Parent Global Assessment (PGA) Scores | 21 Participants |