Attention Deficit Disorder With Hyperactivity
Conditions
Brief summary
The purpose of this study is to assess the safety and efficacy of SPD503 (Guanfacine hydrochloride) compared to placebo in the treatment of ADHD in children and adolescents aged 6-17
Interventions
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with a primary diagnosis of ADHD * 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) 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 Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at Up to 5 Weeks | Baseline and up to 5 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 |
|---|---|---|
| Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at Up to 5 Weeks | Baseline and up to 5 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) reflecting no symptoms to 3 (very much true) reflecting severe symptoms 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. |
| Change From Baseline in Conner's Teacher Rating Scale-revised Short Version (CTRS-R) Score at Up to 5 Weeks | Baseline and up to 5 weeks | The Conner's Teacher Rating Scale-revised short version (CTRS-R) consists of 28 questions graded on a scale from 0 (not true at all) reflecting no symptoms to 3 (very much true) reflecting severe symptoms with a total score ranging from 0 to 84. Higher scores are indicative of increased ADHD. This scale allows teachers to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior. |
| Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | up to 5 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. |
| Number of Participants With Improvement in Parent Global Assessment (PGA) | up to 5 weeks | Parent Global Assessment (PGA) 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 Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Baseline and 5 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 score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. |
Participant flow
Pre-assignment details
Subjects were randomized to receive either 2, 3, or 4 mg SPD503 (Guanfacine hydrochloride) or placebo once-daily.
Participants by arm
| Arm | Count |
|---|---|
| SPD503 2mg Subjects were randomized to receive 2 mg SPD503 (Guanfacine hydrochloride) once-daily. | 87 |
| SPD503 3mg Subjects were randomized to receive 3 mg SPD503 (Guanfacine hydrochloride) once-daily. | 86 |
| SPD503 4mg Subjects were randomized to receive 4 mg SPD503 (Guanfacine hydrochloride) once-daily. | 86 |
| Placebo Subjects were randomized to receive Placebo once-daily. | 86 |
| Total | 345 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 13 | 20 | 1 |
| Overall Study | ECG abnormalities | 2 | 2 | 2 | 1 |
| Overall Study | Lack of Efficacy | 8 | 6 | 7 | 15 |
| Overall Study | Lost to Follow-up | 2 | 4 | 3 | 3 |
| Overall Study | Protocol Violation | 3 | 0 | 0 | 1 |
| Overall Study | Sponsor's decision | 3 | 3 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 4 | 9 |
Baseline characteristics
| Characteristic | SPD503 3mg | SPD503 4mg | SPD503 2mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 86 Participants | 86 Participants | 87 Participants | 86 Participants | 345 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.8 years STANDARD_DEVIATION 2.76 | 10.1 years STANDARD_DEVIATION 2.86 | 10.6 years STANDARD_DEVIATION 2.35 | 10.6 years STANDARD_DEVIATION 2.7 | 10.5 years STANDARD_DEVIATION 2.68 |
| Region of Enrollment United States | 86 Participants | 86 Participants | 87 Participants | 86 Participants | 345 Participants |
| Sex: Female, Male Female | 17 Participants | 29 Participants | 20 Participants | 22 Participants | 88 Participants |
| Sex: Female, Male Male | 69 Participants | 57 Participants | 67 Participants | 64 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 67 / 87 | 76 / 86 | 75 / 86 | 55 / 86 |
| serious Total, serious adverse events | 0 / 87 | 1 / 86 | 1 / 86 | 0 / 86 |
Outcome results
Primary
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at Up to 5 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 up to 5 weeks
Population: Intent to treat (ITT) defined as all subjects who were randomized to treatment and had the baseline and at least one post-randomization primary efficacy measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPD503 2mg | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at Up to 5 Weeks | -15.93 Units on a Scale | Standard Error 1.37 |
| SPD503 3mg | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at Up to 5 Weeks | -16.03 Units on a Scale | Standard Error 1.38 |
| SPD503 4mg | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at Up to 5 Weeks | -18.51 Units on a Scale | Standard Error 1.39 |
| Placebo | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at Up to 5 Weeks | -8.51 Units on a Scale | Standard Error 1.42 |
p-value: 0.0006ANCOVA
p-value: 0.0005ANCOVA
p-value: <0.0001ANCOVA
Secondary
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 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 score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents.
Time frame: Baseline and 5 weeks
Population: ITT
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SPD503 2mg | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Psychosocial | 9.03 Units on a scale | Standard Error 1.22 |
| SPD503 2mg | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Physical | 0.24 Units on a scale | Standard Error 0.84 |
| SPD503 3mg | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Physical | -1.82 Units on a scale | Standard Error 0.84 |
| SPD503 3mg | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Psychosocial | 9.01 Units on a scale | Standard Error 1.2 |
| SPD503 4mg | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Psychosocial | 10.64 Units on a scale | Standard Error 1.32 |
| SPD503 4mg | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Physical | -2.13 Units on a scale | Standard Error 0.92 |
| Placebo | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Psychosocial | 5.72 Units on a scale | Standard Error 1.23 |
| Placebo | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 5 Weeks | Physical | -0.18 Units on a scale | Standard Error 0.86 |
Comparison: Psychosocial categoryp-value: 0.1438ANCOVA
Comparison: Psychosocial categoryp-value: 0.1426ANCOVA
Comparison: Psychosocial categoryp-value: 0.0191ANCOVA
Secondary
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at Up to 5 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) reflecting no symptoms to 3 (very much true) reflecting severe symptoms 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 up to 5 weeks
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPD503 2mg | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at Up to 5 Weeks | -15.59 Units on a Scale | Standard Error 1.86 |
| SPD503 3mg | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at Up to 5 Weeks | -15.43 Units on a Scale | Standard Error 1.95 |
| SPD503 4mg | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at Up to 5 Weeks | -21.49 Units on a Scale | Standard Error 2 |
| Placebo | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at Up to 5 Weeks | -8.66 Units on a Scale | Standard Error 1.87 |
p-value: 0.025ANCOVA
p-value: 0.035ANCOVA
p-value: <0.0001ANCOVA
Secondary
Change From Baseline in Conner's Teacher Rating Scale-revised Short Version (CTRS-R) Score at Up to 5 Weeks
The Conner's Teacher Rating Scale-revised short version (CTRS-R) consists of 28 questions graded on a scale from 0 (not true at all) reflecting no symptoms to 3 (very much true) reflecting severe symptoms with a total score ranging from 0 to 84. Higher scores are indicative of increased ADHD. This scale allows teachers to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior.
Time frame: Baseline and up to 5 weeks
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPD503 2mg | Change From Baseline in Conner's Teacher Rating Scale-revised Short Version (CTRS-R) Score at Up to 5 Weeks | -13.02 Units on a Scale | Standard Error 1.69 |
| SPD503 3mg | Change From Baseline in Conner's Teacher Rating Scale-revised Short Version (CTRS-R) Score at Up to 5 Weeks | -14.88 Units on a Scale | Standard Error 1.79 |
| SPD503 4mg | Change From Baseline in Conner's Teacher Rating Scale-revised Short Version (CTRS-R) Score at Up to 5 Weeks | -15.26 Units on a Scale | Standard Error 1.8 |
| Placebo | Change From Baseline in Conner's Teacher Rating Scale-revised Short Version (CTRS-R) Score at Up to 5 Weeks | -2.17 Units on a Scale | Standard Error 1.7 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I)
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: up to 5 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD503 2mg | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 47 Participants |
| SPD503 3mg | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 41 Participants |
| SPD503 4mg | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 45 Participants |
| Placebo | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 20 Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: 0.0016Cochran-Mantel-Haenszel
p-value: 0.0001Cochran-Mantel-Haenszel
Secondary
Number of Participants With Improvement in Parent Global Assessment (PGA)
Parent Global Assessment (PGA) 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: up to 5 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD503 2mg | Number of Participants With Improvement in Parent Global Assessment (PGA) | 41 Participants |
| SPD503 3mg | Number of Participants With Improvement in Parent Global Assessment (PGA) | 31 Participants |
| SPD503 4mg | Number of Participants With Improvement in Parent Global Assessment (PGA) | 39 Participants |
| Placebo | Number of Participants With Improvement in Parent Global Assessment (PGA) | 15 Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: 0.0013Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel