Attention Deficit Disorder With Hyperactivity
Conditions
Brief summary
The purpose of this study is to determine the efficacy of SPD503 compared to placebo in the treatment of children and adolescents aged 6-17 with ADHD.
Interventions
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with a primary diagnosis of ADHD * Females of childbearing potential must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test * Male or non-pregnant female subject who agrees to comply with any applicable contraceptive requirements
Exclusion criteria
* Subject has a current, uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as severe comorbid Axis II disorders or severe Axis I disorders * Subject weighs less than 55 lbs or is morbidly overweight with a BMI =\> 35 * Subject has a history of seizure during the last 2 years or a serious tic disorder, including Tourette's Disorder * 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 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 |
|---|---|---|
| Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) 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 in Clinical Global Impression-Improvement (CGI-I) | 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. |
| Number of Participants With Improvement in Parent Global Assessment (PGA) | 6 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 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. Increases in scores represent improved well-being in subjects as assessed by their parents. |
Participant flow
Pre-assignment details
Although 324 subjects were randomized, 2 never received drug and therefore were not included in the Baseline Characteristics. Subjects received either 1, 2, 3, or 4 mg of SPD503 (Guanfacine hydrochloride) or placebo once daily.
Participants by arm
| Arm | Count |
|---|---|
| SPD503 (1 mg) Guanfacine HCl once daily | 61 |
| SPD503 (2 mg) Guanfacine HCl once daily | 65 |
| SPD503 (3 mg) Guanfacine HCl once daily | 65 |
| SPD503 (4 mg) Guanfacine HCl once daily | 65 |
| Placebo once daily | 66 |
| Total | 322 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Abnormal ECG | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Adverse Event | 2 | 2 | 6 | 9 | 5 |
| Overall Study | Lack of compliance | 2 | 1 | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 4 | 7 | 4 | 6 |
| Overall Study | Lost to Follow-up | 4 | 1 | 5 | 8 | 4 |
| Overall Study | No study meds | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Physician Decision | 0 | 2 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Sponsor's decision | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 8 | 8 | 4 | 5 |
Baseline characteristics
| Characteristic | SPD503 (2 mg) | SPD503 (3 mg) | SPD503 (4 mg) | SPD503 (1 mg) | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 65 Participants | 65 Participants | 65 Participants | 61 Participants | 66 Participants | 322 Participants |
| Age, Categorical >=65 years | 0 Participants | 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 | 0 Participants |
| Age, Continuous | 10.6 years STANDARD_DEVIATION 2.81 | 11.1 years STANDARD_DEVIATION 2.96 | 10.5 years STANDARD_DEVIATION 2.53 | 9.3 years STANDARD_DEVIATION 2.14 | 10.8 years STANDARD_DEVIATION 2.89 | 10.5 years STANDARD_DEVIATION 2.74 |
| Region of Enrollment United States | 65 Participants | 65 Participants | 65 Participants | 61 Participants | 66 Participants | 322 Participants |
| Sex: Female, Male Female | 19 Participants | 17 Participants | 12 Participants | 20 Participants | 21 Participants | 89 Participants |
| Sex: Female, Male Male | 46 Participants | 48 Participants | 53 Participants | 41 Participants | 45 Participants | 233 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 49 / 61 | 40 / 65 | 45 / 65 | 55 / 65 | 45 / 66 |
| serious Total, serious adverse events | 0 / 61 | 0 / 65 | 1 / 65 | 0 / 65 | 1 / 66 |
Outcome results
Primary
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) 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: 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 (1 mg) | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at 6 Weeks | -19.44 Units on a Scale | Standard Error 1.69 |
| SPD503 (2 mg) | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at 6 Weeks | -18.09 Units on a Scale | Standard Error 1.6 |
| SPD503 (3 mg) | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at 6 Weeks | -20.00 Units on a Scale | Standard Error 1.64 |
| SPD503 (4 mg) | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at 6 Weeks | -20.57 Units on a Scale | Standard Error 1.6 |
| Placebo | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) Score at 6 Weeks | -12.69 Units on a Scale | Standard Error 1.6 |
p-value: 0.0041ANCOVA
p-value: 0.0176ANCOVA
p-value: 0.0016ANCOVA
p-value: 0.0006ANCOVA
Secondary
Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score 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. Increases in scores represent improved well-being in subjects as assessed by their parents.
Time frame: Baseline and 6 weeks
Population: ITT
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SPD503 (1 mg) | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Physical | 0.32 units on a scale | Standard Error 0.87 |
| SPD503 (1 mg) | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Psychosocial | 10.61 units on a scale | Standard Error 1.41 |
| SPD503 (2 mg) | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Psychosocial | 7.47 units on a scale | Standard Error 1.44 |
| SPD503 (2 mg) | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Physical | 0.35 units on a scale | Standard Error 0.89 |
| SPD503 (3 mg) | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Psychosocial | 9.07 units on a scale | Standard Error 1.61 |
| SPD503 (3 mg) | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Physical | -0.91 units on a scale | Standard Error 0.99 |
| SPD503 (4 mg) | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Physical | -2.44 units on a scale | Standard Error 0.95 |
| SPD503 (4 mg) | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Psychosocial | 9.43 units on a scale | Standard Error 1.53 |
| Placebo | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Psychosocial | 6.34 units on a scale | Standard Error 1.49 |
| Placebo | Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF50) Score at 6 Weeks | Physical | -0.01 units on a scale | Standard Error 0.92 |
Comparison: Psychosocial categoryp-value: 0.0383ANCOVA
Comparison: Psychosocial categoryp-value: 0.5859ANCOVA
Comparison: Psychosocial categoryp-value: 0.2136ANCOVA
Comparison: Psychosocial categoryp-value: 0.1483ANCOVA
Secondary
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) 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: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPD503 (1 mg) | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at 6 Weeks | -19.50 Units on a Scale | Standard Error 2.36 |
| SPD503 (2 mg) | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at 6 Weeks | -14.96 Units on a Scale | Standard Error 2.29 |
| SPD503 (3 mg) | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at 6 Weeks | -17.94 Units on a Scale | Standard Error 2.48 |
| SPD503 (4 mg) | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at 6 Weeks | -15.93 Units on a Scale | Standard Error 2.34 |
| Placebo | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) Score at 6 Weeks | -8.41 Units on a Scale | Standard Error 2.34 |
p-value: 0.001ANCOVA
p-value: 0.0468ANCOVA
p-value: 0.0056ANCOVA
p-value: 0.0237ANCOVA
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: 6 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD503 (1 mg) | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 31 Participants |
| SPD503 (2 mg) | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 27 Participants |
| SPD503 (3 mg) | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 33 Participants |
| SPD503 (4 mg) | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 35 Participants |
| Placebo | Number of Participants With Improvement in Clinical Global Impression-Improvement (CGI-I) | 19 Participants |
p-value: 0.0074Cochran-Mantel-Haenszel
p-value: 0.1404Cochran-Mantel-Haenszel
p-value: 0.0055Cochran-Mantel-Haenszel
p-value: 0.0041Cochran-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: 6 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD503 (1 mg) | Number of Participants With Improvement in Parent Global Assessment (PGA) | 27 Participants |
| SPD503 (2 mg) | Number of Participants With Improvement in Parent Global Assessment (PGA) | 20 Participants |
| SPD503 (3 mg) | Number of Participants With Improvement in Parent Global Assessment (PGA) | 29 Participants |
| SPD503 (4 mg) | Number of Participants With Improvement in Parent Global Assessment (PGA) | 30 Participants |
| Placebo | Number of Participants With Improvement in Parent Global Assessment (PGA) | 16 Participants |
p-value: 0.0303Cochran-Mantel-Haenszel
p-value: 0.4982Cochran-Mantel-Haenszel
p-value: 0.0017Cochran-Mantel-Haenszel
p-value: 0.0063Cochran-Mantel-Haenszel