Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Brief summary
Assess the efficacy & tolerability of Vyvanse when children aged 6-12 years diagnosed with ADHD are dosed to optimal effect.
Detailed description
Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (lisdexamfetamine dimesylate) in Children aged 6-12 Diagnosed with ADHD
Interventions
Vyvanse™ 20mg once daily at 7 a.m.; dose increased weekly by 10mg until an acceptable response is achieved. Titration may proceed to a maximum daily dose 70mg/day.
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 based on a detailed psychiatric evaluation. 4. Subjects must have a baseline ADHD-RS-IV total score ≥28. 5. Subject is functioning at an age-appropriate level intellectually. 6. comply with all the testing and requirements. 7. Subject is able to swallow a capsule. 8. Subject has blood pressure measurements within the 95th percentile for age, gender, and height.
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, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder or other symptomatic manifestations. 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. 6. Subject has a positive urine drug result. 7. Subject weighs less than 50 pounds (22.7kg). 8. Subject is significantly overweight. 9. Subject has a history of seizures (exclusive of febrile seizures), a tic disorder, a current diagnosis and/or family history of Tourette's Disorder. 10. Subject has any reported history of abnormal thyroid function. 11. Subject has taken another investigational product or taken part in a clinical trial within 30 days prior to Screening. 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. The female subject is pregnant or lactating. 14. Subject is well-controlled on their current ADHD medication with acceptable tolerability.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Score at 7 Weeks | Baseline and 7 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 |
|---|---|---|
| Weekly Change From Baseline in Total ADHD-RS-IV Score | Baseline and 1, 2, 3, 4, 5, 6, and 7 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. |
| Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) | 7 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 or 2 on the scale. |
| Number of Participants With Improvement onParent Global Assessment (PGA) | 7 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 Expression and Emotional Scale for Children (EESC) Scores at 7 Weeks | Baseline and 7 weeks | Expression and Emotional Scale for Children (EESC) consists of 29 items rated on a scale from 1 (not true at all) to 5 (very much true). Lower scores reflect better emotional outcomes. |
| Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at 7 Weeks | Baseline and 7 weeks | Behavior Rating Inventory of Executive Function (BRIEF) is an 86-item questionnaire composed of three scales (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Lower scores reflect better functioning. |
Countries
United States
Participant flow
Pre-assignment details
The study had three phases; 1)screening and wash-out; 2) dose-optimization (5 weeks) and maintenance (2 weeks); 3) 30-day safety follow-up. Dosing ranged from 20-70 mg once daily of Vyvanse.
Participants by arm
| Arm | Count |
|---|---|
| Vyvanse Lisdexamfetamine dimesylate (LDX) | 318 |
| Total | 318 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 30-day Safety Follow-up | Lost to Follow-up | 17 |
| Dose-optimization and Maintenance Phase | Adverse Event | 13 |
| Dose-optimization and Maintenance Phase | Lack of Efficacy | 2 |
| Dose-optimization and Maintenance Phase | Lack of protocol compliance | 4 |
| Dose-optimization and Maintenance Phase | Protocol Violation | 2 |
| Dose-optimization and Maintenance Phase | Withdrawal by Subject | 1 |
| Screening and Washout Phase | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Vyvanse |
|---|---|
| Age, Categorical <=18 years | 318 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 9.1 years STANDARD_DEVIATION 1.9 |
| Region of Enrollment United States | 318 Participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 225 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 269 / 317 |
| serious Total, serious adverse events | 2 / 317 |
Outcome results
Primary
Change From Baseline in Total Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Score at 7 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 7 weeks
Population: Intent-to-treat (ITT). ITT population defined as all subjects who took at least one dose of drug and had at least one ADHD-RS-IV total score available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Change From Baseline in Total Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Score at 7 Weeks | -28.6 Units on a scale | Standard Error 0.61 |
p-value: <0.0001t-test, 1 sided
Secondary
Change From Baseline in Expression and Emotional Scale for Children (EESC) Scores at 7 Weeks
Expression and Emotional Scale for Children (EESC) consists of 29 items rated on a scale from 1 (not true at all) to 5 (very much true). Lower scores reflect better emotional outcomes.
Time frame: Baseline and 7 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vyvanse | Change From Baseline in Expression and Emotional Scale for Children (EESC) Scores at 7 Weeks | -7.4 Units on a scale | Standard Deviation 18.3 |
p-value: <0.0001t-test, 1 sided
Secondary
Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at 7 Weeks
Behavior Rating Inventory of Executive Function (BRIEF) is an 86-item questionnaire composed of three scales (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Lower scores reflect better functioning.
Time frame: Baseline and 7 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vyvanse | Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at 7 Weeks | Global Executive Composite | -17.9 Units on a scale | Standard Deviation 12.5 |
| Vyvanse | Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at 7 Weeks | Behavioral Recognition Index | -15.4 Units on a scale | Standard Deviation 12.6 |
| Vyvanse | Changes From Baseline in Behavior Rating Inventory of Executive Function (BRIEF) Scores at 7 Weeks | Metacognition Index | -17.6 Units on a scale | Standard Deviation 12.3 |
Comparison: Global Executive Compositep-value: <0.0001t-test, 1 sided
Comparison: Behavioral Recognition Indexp-value: <0.0001t-test, 1 sided
Comparison: Metacognition Indexp-value: <0.0001t-test, 1 sided
Secondary
Number of Participants With Improvement on 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 or 2 on the scale.
Time frame: 7 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vyvanse | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) | 284 Participants |
Secondary
Number of Participants With Improvement onParent 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: 7 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vyvanse | Number of Participants With Improvement onParent Global Assessment (PGA) | 267 Participants |
Secondary
Weekly Change From Baseline in Total ADHD-RS-IV Score
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 1, 2, 3, 4, 5, 6, and 7 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vyvanse | Weekly Change From Baseline in Total ADHD-RS-IV Score | Week 1 | -11.3 Units on a scale | Standard Error 0.62 |
| Vyvanse | Weekly Change From Baseline in Total ADHD-RS-IV Score | Week 2 | -17.8 Units on a scale | Standard Error 0.63 |
| Vyvanse | Weekly Change From Baseline in Total ADHD-RS-IV Score | Week 3 | -21.7 Units on a scale | Standard Error 0.61 |
| Vyvanse | Weekly Change From Baseline in Total ADHD-RS-IV Score | Week 4 | -25.4 Units on a scale | Standard Error 0.61 |
| Vyvanse | Weekly Change From Baseline in Total ADHD-RS-IV Score | Week 5 | -27.0 Units on a scale | Standard Error 0.6 |
| Vyvanse | Weekly Change From Baseline in Total ADHD-RS-IV Score | Week 6 | -28.9 Units on a scale | Standard Error 0.6 |
| Vyvanse | Weekly Change From Baseline in Total ADHD-RS-IV Score | Week 7 | -29.8 Units on a scale | Standard Error 0.58 |
Comparison: Week 1p-value: <0.0001t-test, 1 sided
Comparison: Week 2p-value: <0.0001t-test, 1 sided
Comparison: Week 3p-value: <0.0001t-test, 1 sided
Comparison: Week 4p-value: <0.0001t-test, 1 sided
Comparison: Week 5p-value: <0.0001t-test, 1 sided
Comparison: Week 6p-value: <0.0001t-test, 1 sided
Comparison: Week 7p-value: <0.0001t-test, 1 sided