Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Brief summary
The study will evaluate the efficacy of LDX treatment group compared to placebo on the change from Baseline ADHD-RS-IV score at endpoint.
Interventions
DRUGLDX 30 mg
Eligible subjects will be randomized in a 1:1:1:1 ratio to a daily morning dose of LDX (30, 50, or 70mg/day) or placebo for a double-blind stepwise forced dose titration (3 weeks) followed by a 1-week Dose Maintenance Period. The test product is LDX, available in 30, 50, and 70mg capsules. All test products will appear identical to placebo to protect the study blind.
DRUGLDX 50 mg
Eligible subjects will be randomized in a 1:1:1:1 ratio to a daily morning dose of LDX (30, 50, or 70mg/day) or placebo for a double-blind stepwise forced dose titration (3 weeks) followed by a 1-week Dose Maintenance Period. The test product is LDX, available in 30, 50, and 70mg capsules. All test products will appear identical to placebo to protect the study blind.
DRUGLDX 70 mg
Eligible subjects will be randomized in a 1:1:1:1 ratio to a daily morning dose of LDX (30, 50, or 70mg/day) or placebo for a double-blind stepwise forced dose titration (3 weeks) followed by a 1-week Dose Maintenance Period. The test product is LDX, available in 30, 50, and 70mg capsules. All test products will appear identical to placebo to protect the study blind.
DRUGPlacebo
Placebo will be identical to test product.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Meet DSM-IV-TR criteria for a primary diagnosis of ADHD * Baseline ADHD-RS-IV score \>=28 * BP w/in 95th percentile for age, gender, and height
Exclusion criteria
* Subject has controlled or uncontrolled comorbid psychiatric diagnosis * Subject has conduct disorder * Suicidal * Under or overweight * Concurrent chronic or acute illness that might confound results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 4 Weeks | Baseline and 1, 2, 3 and 4 weeks | 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 | 1, 2, 3 and 4 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. |
| Youth Quality of Life-Research Version (YQOL-R) Total Score | Baseline and 4 weeks | The Youth Quality of Life-research version (YQOL-R) is a validated 56-item generic instrument for comparing quality of life of adolescents across condition groups that scores each question on a scale from 0 (never) to 4 (very often). The YQOL scores are transformed to a 0-100 scale for easy interpretability. Higher scores indicate better quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lisdexamfetamine Dimesylate (LDX) 30 mg Subjects will be randomized in a 1:1:1:1 ratio to a daily morning dose of Lisdexamfetamine dimesylate (LDX) 30, 50, or 70mg/day or placebo for a double-blind stepwise forced dose titration (3 weeks) followed by a 1-week Dose Maintenance Period. | 78 |
| LDX 50 mg Subjects will be randomized in a 1:1:1:1 ratio to a daily morning dose of Lisdexamfetamine dimesylate (LDX) 30, 50, or 70mg/day or placebo for a double-blind stepwise forced dose titration (3 weeks) followed by a 1-week Dose Maintenance Period. | 79 |
| LDX 70 mg Subjects will be randomized in a 1:1:1:1 ratio to a daily morning dose of Lisdexamfetamine dimesylate (LDX) 30, 50, or 70mg/day or placebo for a double-blind stepwise forced dose titration (3 weeks) followed by a 1-week Dose Maintenance Period. | 78 |
| Placebo Placebo | 79 |
| Total | 314 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 4 | 1 |
| Overall Study | Exclusion criteria | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 4 | 2 | 0 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 | 3 | 1 |
| Overall Study | Prior Vyvanse Exposure | 1 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 2 | 0 | 3 |
| Overall Study | Sponsor Decision | 3 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Lisdexamfetamine Dimesylate (LDX) 30 mg | LDX 50 mg | LDX 70 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 78 Participants | 79 Participants | 78 Participants | 79 Participants | 314 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 | 14.6 years STANDARD_DEVIATION 1.39 | 14.7 years STANDARD_DEVIATION 1.29 | 14.4 years STANDARD_DEVIATION 1.3 | 14.5 years STANDARD_DEVIATION 1.25 | 14.6 years STANDARD_DEVIATION 1.31 |
| Region of Enrollment United States | 78 Participants | 79 Participants | 78 Participants | 79 Participants | 314 Participants |
| Sex: Female, Male Female | 19 Participants | 16 Participants | 34 Participants | 25 Participants | 94 Participants |
| Sex: Female, Male Male | 59 Participants | 63 Participants | 44 Participants | 54 Participants | 220 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 | 51 / 78 | 53 / 77 | 56 / 78 | 38 / 77 |
| serious Total, serious adverse events | 0 / 78 | 0 / 77 | 0 / 78 | 0 / 77 |
Outcome results
Primary
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 4 Weeks
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 and 4 weeks
Population: Full Analysis Set (FAS) is defined as all subjects who took at least one dose of study medication and had a valid Baseline and at least one post-Baseline follow-up assessment of the primary outcome measure (ADHD-RS-IV Total Score)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX) 30 mg | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 4 Weeks | -18.3 Units on a scale | Standard Error 1.25 |
| LDX 50 mg | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 4 Weeks | -21.1 Units on a scale | Standard Error 1.28 |
| LDX 70 mg | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 4 Weeks | -20.7 Units on a scale | Standard Error 1.25 |
| Placebo | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 4 Weeks | -12.8 Units on a scale | Standard Error 1.25 |
p-value: 0.0056ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
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: 1, 2, 3 and 4 Weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisdexamfetamine Dimesylate (LDX) 30 mg | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 44 Participants |
| LDX 50 mg | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 53 Participants |
| LDX 70 mg | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 57 Participants |
| Placebo | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 30 Participants |
p-value: 0.0235Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Youth Quality of Life-Research Version (YQOL-R) Total Score
The Youth Quality of Life-research version (YQOL-R) is a validated 56-item generic instrument for comparing quality of life of adolescents across condition groups that scores each question on a scale from 0 (never) to 4 (very often). The YQOL scores are transformed to a 0-100 scale for easy interpretability. Higher scores indicate better quality of life.
Time frame: Baseline and 4 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX) 30 mg | Youth Quality of Life-Research Version (YQOL-R) Total Score | 4 Weeks | 81.1 Units on a scale | Standard Deviation 11.09 |
| Lisdexamfetamine Dimesylate (LDX) 30 mg | Youth Quality of Life-Research Version (YQOL-R) Total Score | Baseline | 79.3 Units on a scale | Standard Deviation 10.03 |
| LDX 50 mg | Youth Quality of Life-Research Version (YQOL-R) Total Score | 4 Weeks | 81.3 Units on a scale | Standard Deviation 11.86 |
| LDX 50 mg | Youth Quality of Life-Research Version (YQOL-R) Total Score | Baseline | 80.5 Units on a scale | Standard Deviation 10.63 |
| LDX 70 mg | Youth Quality of Life-Research Version (YQOL-R) Total Score | Baseline | 78.8 Units on a scale | Standard Deviation 15.38 |
| LDX 70 mg | Youth Quality of Life-Research Version (YQOL-R) Total Score | 4 Weeks | 81.3 Units on a scale | Standard Deviation 14.66 |
| Placebo | Youth Quality of Life-Research Version (YQOL-R) Total Score | Baseline | 79.2 Units on a scale | Standard Deviation 11.08 |
| Placebo | Youth Quality of Life-Research Version (YQOL-R) Total Score | 4 Weeks | 81.3 Units on a scale | Standard Deviation 12.16 |