ADHD
Conditions
Brief summary
The primary objective of this study is to assess the time of onset of Vyvanse compared to placebo, in the analog classroom as measured by the Swanson, Kotkin, Agler, M. Flynn and Pelham (SKAMP) deportment scale in children (aged 6-12) diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD).
Interventions
Following completion of the open-label dose optimization period and successful titration to an optimal dose of Vyvanse™, subjects will take their optimized dose of Vyvanse™ (30, 50 or 70 mg/day).
DRUGPlacebo
Placebo
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is a male or female aged 6-12 years inclusive at the time of consent. 2. Females of Child-bearing Potential (FOCP) must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to comply with any applicable contraceptive requirements of the protocol. 3. Primary diagnosis of ADHD: combined sub-type or predominantly hyperactive impulsive sub-type based on a detailed psychiatric evaluation. 4. Subject has a baseline ADHD-RS-IV score ≥ 28. 5. Intelligent Quotient (IQ) score of 80 or above on the Kaufman Brief Intelligence Test (KBIT). 6. Subject must be able to complete at least the Basic Test of the PERMP assessment.
Exclusion criteria
1. Subject has a current, controlled (requiring a restricted medication) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as Post Traumatic Stress Disorder (PTSD), psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder 2. Subject has Conduct Disorder. 3. Subject has a documented allergy, hypersensitivity or intolerance to amphetamines. 4. Subject has failed to respond to one or more adequate courses (dose and duration) of amphetamine therapy. 5. The subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-IV-TR criteria. 6. Subject weighs less than 50 pounds (22.7kg). 7. Subject is significantly overweight 8. Subject had a history of seizures during the last two years (exclusive of febrile seizures), a tic disorder, a current diagnosis and/or family history of Tourette's Disorder. 9. Subject has any reported history of abnormal thyroid function. 10. Subject has taken another investigational drug or taken part in a clinical trial within the last 30 days prior to Screening. 11. Subject has a known history of structural cardiac abnormality, as well as any other condition(s) that may affect cardiac performance. 12. Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments 13. Subject is taking other medications that have central nervous system (CNS) effects or affect performance, such as sedating antihistamines and decongestant sympathomimetics (bronchodilators are not exclusionary). 14. The female subject is pregnant or lactating. 15. Subject is well controlled on their current ADHD medication with acceptable tolerability.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Onset of Effect of Vyvanse | Evaluations were conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose. | The onset of effect will be defined as the first assessment time showing statistical significance between Vyvanse and placebo as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Deportment scale. The degree of impairment is rated from 0 (normal) to 6 (maximal). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Effect of Vyvanse | Evaluations were conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose. | Duration of effect will be defined as the first time point at which there is a non-significant difference between Vyvanse and placebo after a time point at which there is a significant difference between the two treatment groups as measured by SKAMP Deportment Scores. The degree of impairment is rated from 0 (normal) to 6 (maximal). |
Countries
United States
Participant flow
Recruitment details
129 subjects were enrolled for dose optimization phase, 12 discontinued, and 117 were randomized to the cross-over phase.
Pre-assignment details
The study consisted of an open-label dose-optimization phase (4 weeks), followed by a randomized, placebo-controlled, 2-way crossover phase (1 week each).
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population | 129 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Enrolled (Dose-optimization Phase) | Adverse Event | 8 | 0 |
| Enrolled (Dose-optimization Phase) | Protocol Violation | 1 | 0 |
| Enrolled (Dose-optimization Phase) | Withdrawal by Subject | 3 | 0 |
| First Intervention (Cross-over Phase) | Adverse Event | 0 | 1 |
| First Intervention (Cross-over Phase) | Protocol Violation | 1 | 0 |
| First Intervention (Cross-over Phase) | Withdrawal by Subject | 1 | 1 |
| Second Intervention (Cross-over Phase) | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Categorical <=18 years | 129 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 10.1 years STANDARD_DEVIATION 1.5 |
| Region of Enrollment United States | 129 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 115 | 3 / 115 |
| serious Total, serious adverse events | 0 / 115 | 0 / 115 |
Outcome results
Primary
Onset of Effect of Vyvanse
The onset of effect will be defined as the first assessment time showing statistical significance between Vyvanse and placebo as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Deportment scale. The degree of impairment is rated from 0 (normal) to 6 (maximal).
Time frame: Evaluations were conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose.
Population: Analysis on the intention-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Vyvanse | Onset of Effect of Vyvanse | 5 hours | 0.44 scores on a scale | Standard Error 0.1 |
| Vyvanse | Onset of Effect of Vyvanse | 10 hours | 0.60 scores on a scale | Standard Error 0.09 |
| Vyvanse | Onset of Effect of Vyvanse | 2.5 hours | 0.45 scores on a scale | Standard Error 0.09 |
| Vyvanse | Onset of Effect of Vyvanse | 12 hours | 0.90 scores on a scale | Standard Error 0.1 |
| Vyvanse | Onset of Effect of Vyvanse | 7.5 hours | 0.54 scores on a scale | Standard Error 0.09 |
| Vyvanse | Onset of Effect of Vyvanse | 13 hours | 1.05 scores on a scale | Standard Error 0.1 |
| Vyvanse | Onset of Effect of Vyvanse | 1.5 hours | 0.70 scores on a scale | Standard Error 0.09 |
| Placebo | Onset of Effect of Vyvanse | 13 hours | 1.31 scores on a scale | Standard Error 0.1 |
| Placebo | Onset of Effect of Vyvanse | 1.5 hours | 1.14 scores on a scale | Standard Error 0.09 |
| Placebo | Onset of Effect of Vyvanse | 2.5 hours | 1.42 scores on a scale | Standard Error 0.09 |
| Placebo | Onset of Effect of Vyvanse | 5 hours | 1.60 scores on a scale | Standard Error 0.1 |
| Placebo | Onset of Effect of Vyvanse | 7.5 hours | 1.56 scores on a scale | Standard Error 0.09 |
| Placebo | Onset of Effect of Vyvanse | 10 hours | 1.43 scores on a scale | Standard Error 0.09 |
| Placebo | Onset of Effect of Vyvanse | 12 hours | 1.41 scores on a scale | Standard Error 0.1 |
Comparison: Statistical analysis of SKAMP scores at 1.5 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 2.5 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 5.0 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 7.5 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 10.0 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 12.0 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 13.0 hours post-dosep-value: <0.0001ANCOVA
Secondary
Duration of Effect of Vyvanse
Duration of effect will be defined as the first time point at which there is a non-significant difference between Vyvanse and placebo after a time point at which there is a significant difference between the two treatment groups as measured by SKAMP Deportment Scores. The degree of impairment is rated from 0 (normal) to 6 (maximal).
Time frame: Evaluations were conducted at 1.5, 2.5, 5.0, 7.5, 10.0, 12.0, and 13.0 hours post-dose.
Population: Analysis on intention-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Vyvanse | Duration of Effect of Vyvanse | 7.5 hours | 0.54 scores on a scale | Standard Error 0.09 |
| Vyvanse | Duration of Effect of Vyvanse | 10 hours | 0.60 scores on a scale | Standard Error 0.09 |
| Vyvanse | Duration of Effect of Vyvanse | 1.5 hours | 0.70 scores on a scale | Standard Error 0.09 |
| Vyvanse | Duration of Effect of Vyvanse | 12 hours | 0.90 scores on a scale | Standard Error 0.1 |
| Vyvanse | Duration of Effect of Vyvanse | 5 hours | 0.44 scores on a scale | Standard Error 0.1 |
| Vyvanse | Duration of Effect of Vyvanse | 13 hours | 1.05 scores on a scale | Standard Error 0.1 |
| Vyvanse | Duration of Effect of Vyvanse | 2.5 hours | 0.45 scores on a scale | Standard Error 0.09 |
| Placebo | Duration of Effect of Vyvanse | 13 hours | 1.31 scores on a scale | Standard Error 0.1 |
| Placebo | Duration of Effect of Vyvanse | 1.5 hours | 1.14 scores on a scale | Standard Error 0.09 |
| Placebo | Duration of Effect of Vyvanse | 2.5 hours | 1.42 scores on a scale | Standard Error 0.09 |
| Placebo | Duration of Effect of Vyvanse | 5 hours | 1.60 scores on a scale | Standard Error 0.1 |
| Placebo | Duration of Effect of Vyvanse | 10 hours | 1.43 scores on a scale | Standard Error 0.09 |
| Placebo | Duration of Effect of Vyvanse | 12 hours | 1.41 scores on a scale | Standard Error 0.1 |
| Placebo | Duration of Effect of Vyvanse | 7.5 hours | 1.56 scores on a scale | Standard Error 0.09 |
Comparison: Statistical analysis of SKAMP scores at 1.5 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 2.5 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 5.0 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 7.5 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 10.0 hours post-dosep-value: <0.0001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 12.0 hours post-dosep-value: <0.001ANCOVA
Comparison: Statistical analysis of SKAMP scores at 13.0 hours post-dosep-value: <0.0001ANCOVA