ADHD
Conditions
Brief summary
The main aim of this study is to evaluate the long-term maintenance of efficacy of LDX after administered to children and adolescents aged 6-17 with ADHD for at least 6 months
Interventions
LDX 30, 50, or 70mg capsule once per day (open-label and double-blind periods)
DRUGPlacebo
Placebo capsule once per day (double-blind period)
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Subject's parent or legally authorised representative(LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the subject indicating that the subject is aware of the investigational nature of the study and the required procedures and restrictions in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations before completing any study-related procedures. 2. Subject and parent/LAR are willing and able to comply with all the testing and requirements defined in this protocol, including oversight of morning dosing. Specifically, the parent/LAR must be available upon awakening, at approximately 7:00AM, to dispense the dose of test product for the duration of the study. 3. Subject is a male or female aged 6-17 years inclusive at the time of consent for the antecedent study (SPD489-325). 4. Subject satisfied all entry criteria for the antecedent study (SPD489-325), and completed a minimum of 4 weeks of double-blind treatment, reached Visit 4 and completed the 1-week post-treatment washout in the antecedent study (SPD489-325), without experiencing any clinically significant AEs that would preclude exposure to LDX. 5. Subject must have a satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination findings and clinical laboratory test results. 6. Subject has blood pressure measurements within the 95th percentile for age, gender, and height.
Exclusion criteria
1. Subject was terminated from SPD489-325 for non-compliance and/or experienced an SAE or AE resulting in termination from the antecedent study. 2. Subject has a current, controlled (requiring a restricted medication) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any severe comorbid Axis II disorder or severe Axis I disorder (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, such as agitated states, marked anxiety, or tension that, in the opinion of the examining clinician, will contraindicate treatment with LDX or confound efficacy or safety assessments. Comorbid psychiatric diagnoses will be established at the Screening Visit (Visit -1)of the antecedent study (SPD489-325)with the Screening interview of the Kiddie-SADS-Present and Lifetime-Diagnostic Interview (K-SADS-PL)and additional modules if warranted by the results of the initial interview. Participation in behavioural therapy is permitted provided the subject was receiving the therapy for at least 1 month at the time of the Baseline Visit (Visit 0) of the antecedent study (SPD489-325). 3. Subject has a conduct disorder. Oppositional defiant disorder is not exclusionary. 4. Subject has any concurrent chronic or acute illness or unstable medical condition that could confound the results of safety assessments, increase risk to the subject or lead to difficulty complying with the protocol. 5. Subject is currently considered a suicide risk, has previously made a suicide attempt or has a prior history of, or is currently, demonstrating active suicidal ideation. 6. Subject is female and is pregnant or lactating. 7. Subject has glaucoma. 8. Subject has any clinically significant ECG at Visit 8 of the antecedent study (SPD489-325) or clinically significant laboratory abnormalities at Visit 7 of the antecedent study (SPD489-325). 9. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine. 10. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine)in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR)criteria. 11. Subject has a history of seizures (other than infantile febrile seizures), a tic disorder, a current diagnosis and or a known family history of Tourette's Disorder. 12. Subject has a known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug. 13. Subject has a known family history of sudden cardiac death or ventricular arrhythmia. 14. Subject is taking any medication that is excluded. 15. Subject is taking other medications that have central nervous system (CNS) effects, affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors (during or within 14 days of investigational medicinal product administration). Stable use of bronchodilator inhalers is not exclusionary. 16. Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the investigational medicinal product(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Treatment Failures at End of The Randomized Withdrawal Period | Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks) | Treatment failure defined as 50% increase (worsening) in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) total score and \>= 2 point increase (worsening) in the Clinical Global Impression-Severity of Illness (CGI-S) score observed at any visit during the randomized withdrawal period compared to the respective scores at baseline of randomized withdrawal period. Subjects without an endpoint value were classed as treatment failures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Open-label Baseline in The Health Utilities Index-2 (HUI-2) Scores at Endpoint (Week-26) of The Open-label Period, LOCF | At open-label baseline and endpoint (Week-26) of the open-label period | HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status. |
| Change From Open-Label Baseline in The Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Endpoint (Week-26) of The Open-label Period | At open-label baseline and endpoint (Week-26) of the open-label period | The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. |
| Change From Randomized Withdrawal Baseline in The WFIRS-P Global Score at Endpoint of The Randomized Withdrawal Period | Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks) | The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment. |
| Change From Open-Label Baseline in The Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Endpoint (Week-26) of The Open-label Period | At open-label baseline and endpoint (Week-26) of the open-label period | The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology. |
| Change From Randomized Withdrawal Baseline in BPRS-C Total Score at Endpoint of The Randomized Withdrawal Period | Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks) | The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology. |
| Change From Open-Label Baseline in The Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at Endpoint (Week-26) of The Open-label Period | Open-label baseline and Endpoint (Week-26) | ADHD-RS-IV consists of 18 items scored on a 4-point scale from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology. |
| Change From Randomized Withdrawal Baseline in The ADHD-RS-IV Total Score at Endpoint of The Randomized Withdrawal Period | Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks) | ADHD-RS-IV consists of 18 items scored on a 4-point scale from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology. |
| Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period | At Week 26 | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | At endpoint of the randomized withdrawal period (Up to 6 weeks) | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Percent of Participants With Improvement on Clinical Global Impression - Improvement (CGI-I) at Endpoint (Week-26) of The Open-label Period | At Week 26 | 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. Improvement includes CGI-I categories of very much improved and much improved. No improvement includes all other assessed categories. |
| Change From Randomized Withdrawal Baseline in The HUI-2 Scores at Endpoint of The Randomized Withdrawal Period | Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks) | HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status. |
| Change From Open-label Baseline in The Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF) Global T-score at Endpoint (Week-26) of The Open-label Period | At open-label baseline and endpoint (Week-26) of the open-label period | The CHIP-CE:PRF evaluates health-related quality of life. It is composed of 5 domains (satisfaction, comfort, resilience, avoidance, and achievement) consisting of a total of 76 items. The global score is an average of the scores for the 5 domains. The majority of items assess frequency of events using a 5-point response format. There is no range for a total score. Raw scale scores are used to generate T-scores. Higher scores indicate better health. |
| Change From Randomized Withdrawal Baseline in The CHIP-CE:PRF Global T-score at Endpoint of The Randomized Withdrawal Period | Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks) | The CHIP-CE:PRF evaluates health-related quality of life. It is composed of 5 domains (satisfaction, comfort, resilience, avoidance, and achievement) consisting of a total of 76 items. The global score is an average of the scores for the 5 domains. The majority of items assess frequency of events using a 5-point response format. There is no range for a total score. Raw scale scores are used to generate T-scores. Higher scores indicate better health. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Columbia-Suicide Severity Rating Scale (C-SSRS) During The Open-label Period | From open-label baseline to Week-26 | C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale. |
| C-SSRS During the Randomized Withdrawal Period | Baseline of the randomized withdrawal period to end of the study (Up to 6 weeks) | C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale. |
| Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Randomized withdrawal baseline | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Percent of Participants With CGI-S at Open-label Baseline | Open-label baseline | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). |
Countries
Belgium, France, Germany, Hungary, Italy, Poland, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
In the Open-label period, 8 subjects completed the Open-label period and were not randomized. Therefore, 157 subjects were randomized in the Randomized Withdrawal Period.
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled Subjects | 276 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open-Label Period (Non-Randomized) | ADHD-RS score too high for Random Phase | 1 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Adverse Event | 44 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Decision of medical monitor | 1 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Did not provide end of study page | 1 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Home situation intolerable | 1 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Lack of Efficacy | 21 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Lost to Follow-up | 11 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Met stopping criteria for CGI-S score | 1 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Mother is a drug addict | 1 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Protocol Violation | 7 | 0 | 0 |
| Open-Label Period (Non-Randomized) | Withdrawal by Subject | 22 | 0 | 0 |
| Randomized Withdrawal Period | Adverse Event | 0 | 1 | 1 |
| Randomized Withdrawal Period | Did not complete a visit | 0 | 1 | 0 |
| Randomized Withdrawal Period | Family reasons | 0 | 0 | 1 |
| Randomized Withdrawal Period | Lack of Efficacy | 0 | 5 | 18 |
| Randomized Withdrawal Period | Met relapse criteria per investigator | 0 | 8 | 35 |
| Randomized Withdrawal Period | Protocol Violation | 0 | 2 | 1 |
| Randomized Withdrawal Period | Withdrawal by Subject | 0 | 1 | 7 |
Baseline characteristics
| Characteristic | All Enrolled Subjects |
|---|---|
| Age, Continuous | 10.9 years STANDARD_DEVIATION 2.82 |
| Age, Customized 13-17 years | 85 Participants |
| Age, Customized 6-12 years | 191 Participants |
| Region of Enrollment Belgium | 9 Participants |
| Region of Enrollment France | 11 Participants |
| Region of Enrollment Germany | 95 Participants |
| Region of Enrollment Hungary | 28 Participants |
| Region of Enrollment Italy | 20 Participants |
| Region of Enrollment Poland | 8 Participants |
| Region of Enrollment Sweden | 49 Participants |
| Region of Enrollment United Kingdom | 16 Participants |
| Region of Enrollment United States | 40 Participants |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 212 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 227 / 276 | 31 / 78 | 20 / 79 |
| serious Total, serious adverse events | 12 / 276 | 0 / 78 | 1 / 79 |
Outcome results
Primary
Percent of Participants With Treatment Failures at End of The Randomized Withdrawal Period
Treatment failure defined as 50% increase (worsening) in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) total score and \>= 2 point increase (worsening) in the Clinical Global Impression-Severity of Illness (CGI-S) score observed at any visit during the randomized withdrawal period compared to the respective scores at baseline of randomized withdrawal period. Subjects without an endpoint value were classed as treatment failures.
Time frame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Population: Randomized Full Analysis Set (Randomized FAS) includes all subjects who were randomized and received at least 1 dose of investigational product during the Randomized Withdrawal Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Treatment Failures at End of The Randomized Withdrawal Period | 15.8 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With Treatment Failures at End of The Randomized Withdrawal Period | 67.5 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Change From Open-Label Baseline in The Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at Endpoint (Week-26) of The Open-label Period
ADHD-RS-IV consists of 18 items scored on a 4-point scale from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology.
Time frame: Open-label baseline and Endpoint (Week-26)
Population: Open-label Full Analysis set (Open-label FAS) includes all subjects who received at least 1 dose of investigational product during the Open-label Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Open-Label Baseline in The Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at Endpoint (Week-26) of The Open-label Period | -26.6 Scores on a scale | Standard Deviation 11.39 |
p-value: <0.001t-test, 2 sided
Secondary
Change From Open-Label Baseline in The Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Endpoint (Week-26) of The Open-label Period
The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology.
Time frame: At open-label baseline and endpoint (Week-26) of the open-label period
Population: Open-label Safety Population includes all subjects who received at least 1 dose of investigational product in the Open-label period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Open-Label Baseline in The Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Endpoint (Week-26) of The Open-label Period | -13.9 Scores on a scale | Standard Deviation 12.58 |
Secondary
Change From Open-label Baseline in The Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF) Global T-score at Endpoint (Week-26) of The Open-label Period
The CHIP-CE:PRF evaluates health-related quality of life. It is composed of 5 domains (satisfaction, comfort, resilience, avoidance, and achievement) consisting of a total of 76 items. The global score is an average of the scores for the 5 domains. The majority of items assess frequency of events using a 5-point response format. There is no range for a total score. Raw scale scores are used to generate T-scores. Higher scores indicate better health.
Time frame: At open-label baseline and endpoint (Week-26) of the open-label period
Population: Open-label FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Open-label Baseline in The Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF) Global T-score at Endpoint (Week-26) of The Open-label Period | 10.2 T-scores | Standard Deviation 10.71 |
p-value: <0.001t-test, 1 sided
Secondary
Change From Open-label Baseline in The Health Utilities Index-2 (HUI-2) Scores at Endpoint (Week-26) of The Open-label Period, LOCF
HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.
Time frame: At open-label baseline and endpoint (Week-26) of the open-label period
Population: Open-label FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Open-label Baseline in The Health Utilities Index-2 (HUI-2) Scores at Endpoint (Week-26) of The Open-label Period, LOCF | 0.087 scores on a scale | Standard Deviation 0.1307 |
Secondary
Change From Open-Label Baseline in The Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Endpoint (Week-26) of The Open-label Period
The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.
Time frame: At open-label baseline and endpoint (Week-26) of the open-label period
Population: Open-label FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Open-Label Baseline in The Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Endpoint (Week-26) of The Open-label Period | -0.43 scores on a scale | Standard Deviation 0.42 |
p-value: <0.001t-test, 1 sided
Secondary
Change From Randomized Withdrawal Baseline in BPRS-C Total Score at Endpoint of The Randomized Withdrawal Period
The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology.
Time frame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Population: Randomized Safety Population includes all subjects who received at least 1 dose of any investigational product during the Randomized Withdrawal Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Randomized Withdrawal Baseline in BPRS-C Total Score at Endpoint of The Randomized Withdrawal Period | -17.1 Scores on a scale | Standard Deviation 11.17 |
| Placebo (Randomized Period) | Change From Randomized Withdrawal Baseline in BPRS-C Total Score at Endpoint of The Randomized Withdrawal Period | -9.1 Scores on a scale | Standard Deviation 11.26 |
Secondary
Change From Randomized Withdrawal Baseline in The ADHD-RS-IV Total Score at Endpoint of The Randomized Withdrawal Period
ADHD-RS-IV consists of 18 items scored on a 4-point scale from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology.
Time frame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Population: Randomized FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Randomized Withdrawal Baseline in The ADHD-RS-IV Total Score at Endpoint of The Randomized Withdrawal Period | 1.2 Scores on a scale | Standard Error 1.09 |
| Placebo (Randomized Period) | Change From Randomized Withdrawal Baseline in The ADHD-RS-IV Total Score at Endpoint of The Randomized Withdrawal Period | 13.8 Scores on a scale | Standard Error 1.06 |
p-value: <0.00195% CI: [-15.4, -9.8]ANCOVA
Secondary
Change From Randomized Withdrawal Baseline in The CHIP-CE:PRF Global T-score at Endpoint of The Randomized Withdrawal Period
The CHIP-CE:PRF evaluates health-related quality of life. It is composed of 5 domains (satisfaction, comfort, resilience, avoidance, and achievement) consisting of a total of 76 items. The global score is an average of the scores for the 5 domains. The majority of items assess frequency of events using a 5-point response format. There is no range for a total score. Raw scale scores are used to generate T-scores. Higher scores indicate better health.
Time frame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Population: Randomized FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Randomized Withdrawal Baseline in The CHIP-CE:PRF Global T-score at Endpoint of The Randomized Withdrawal Period | 1.1 T-scores | Standard Error 1.17 |
| Placebo (Randomized Period) | Change From Randomized Withdrawal Baseline in The CHIP-CE:PRF Global T-score at Endpoint of The Randomized Withdrawal Period | -5.4 T-scores | Standard Error 1.1 |
p-value: <0.00195% CI: [3.5, 9.5]ANCOVA
Secondary
Change From Randomized Withdrawal Baseline in The HUI-2 Scores at Endpoint of The Randomized Withdrawal Period
HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.
Time frame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Population: Randomized FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Randomized Withdrawal Baseline in The HUI-2 Scores at Endpoint of The Randomized Withdrawal Period | -0.005 Scores on a scale | Standard Deviation 0.0772 |
| Placebo (Randomized Period) | Change From Randomized Withdrawal Baseline in The HUI-2 Scores at Endpoint of The Randomized Withdrawal Period | -0.046 Scores on a scale | Standard Deviation 0.1098 |
Secondary
Change From Randomized Withdrawal Baseline in The WFIRS-P Global Score at Endpoint of The Randomized Withdrawal Period
The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.
Time frame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Population: Randomized FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Change From Randomized Withdrawal Baseline in The WFIRS-P Global Score at Endpoint of The Randomized Withdrawal Period | 0.01 Scores on a scale | Standard Error 0.03 |
| Placebo (Randomized Period) | Change From Randomized Withdrawal Baseline in The WFIRS-P Global Score at Endpoint of The Randomized Withdrawal Period | 0.20 Scores on a scale | Standard Error 0.03 |
p-value: <0.00195% CI: [-0.26, -0.11]ANCOVA
Secondary
Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: At endpoint of the randomized withdrawal period (Up to 6 weeks)
Population: Randomized FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Borderline mentally ill | 41.3 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Markedly ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Normal, not at all ill | 40.0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Severely ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Moderately ill | 10.7 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Among the most extremely ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Mildly ill | 8.0 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Among the most extremely ill | 0 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Mildly ill | 11.0 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Normal, not at all ill | 8.2 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Borderline mentally ill | 19.2 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Moderately ill | 39.7 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Markedly ill | 15.1 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF) | Severely ill | 6.8 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: At Week 26
Population: Open-label FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period | Normal, not at all ill | 39.9 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period | Borderline mentally ill | 46.5 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period | Mildly ill | 1.5 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period | Moderately ill | 6.6 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period | Markedly ill | 4.5 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period | Severely ill | 0.5 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period | Among the most extremely ill | 0.5 percentage of participants |
Secondary
Percent of Participants With Improvement on Clinical Global Impression - Improvement (CGI-I) at Endpoint (Week-26) of The Open-label Period
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. Improvement includes CGI-I categories of very much improved and much improved. No improvement includes all other assessed categories.
Time frame: At Week 26
Population: Open-label FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With Improvement on Clinical Global Impression - Improvement (CGI-I) at Endpoint (Week-26) of The Open-label Period | 79.8 percentage of improved participants |
Other Pre-specified
Columbia-Suicide Severity Rating Scale (C-SSRS) During The Open-label Period
C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.
Time frame: From open-label baseline to Week-26
Population: Open-label Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Columbia-Suicide Severity Rating Scale (C-SSRS) During The Open-label Period | Suicidal ideation | 1 participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Columbia-Suicide Severity Rating Scale (C-SSRS) During The Open-label Period | Suicidal behavior | 0 participants |
Other Pre-specified
C-SSRS During the Randomized Withdrawal Period
C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.
Time frame: Baseline of the randomized withdrawal period to end of the study (Up to 6 weeks)
Population: Randomized Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | C-SSRS During the Randomized Withdrawal Period | Suicidal ideation | 0 participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | C-SSRS During the Randomized Withdrawal Period | Suicidal behavior | 0 participants |
| Placebo (Randomized Period) | C-SSRS During the Randomized Withdrawal Period | Suicidal ideation | 0 participants |
| Placebo (Randomized Period) | C-SSRS During the Randomized Withdrawal Period | Suicidal behavior | 0 participants |
Other Pre-specified
Percent of Participants With CGI-S at Open-label Baseline
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill).
Time frame: Open-label baseline
Population: Open-label FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Open-label Baseline | Normal, not at all ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Open-label Baseline | Borderline mentally ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Open-label Baseline | Mildly ill | 1.5 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Open-label Baseline | Moderately ill | 27.2 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Open-label Baseline | Markedly ill | 50.2 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Open-label Baseline | Severely ill | 17.6 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Open-label Baseline | Among the most extremely ill | 3.4 percentage of participants |
Other Pre-specified
Percent of Participants With CGI-S at Randomized Withdrawal Baseline
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: Randomized withdrawal baseline
Population: Randomized FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Mildly ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Markedly ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Borderline mentally ill | 50.0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Severely ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Moderately ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Among the most extremely ill | 0 percentage of participants |
| Lisdexamfetamine Dimesylate (LDX)(Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Normal, not at all ill | 50.0 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Among the most extremely ill | 0 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Normal, not at all ill | 46.8 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Borderline mentally ill | 53.2 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Mildly ill | 0 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Moderately ill | 0 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Markedly ill | 0 percentage of participants |
| Placebo (Randomized Period) | Percent of Participants With CGI-S at Randomized Withdrawal Baseline | Severely ill | 0 percentage of participants |
p-value: 0.726Cochran-Mantel-Haenszel