Attention-deficit/Hyperactivity Disorder
Conditions
Keywords
ADHD
Brief summary
The purpose of this study is to determine effectiveness of Vyvanse compared to Concerta in adolescents with Attention-deficit/Hyperactivity Disorder (ADHD).
Interventions
DRUGLisdexamfetamine dimesylate
Daily oral dosing in the AM of optimized dose, ranging from 30- 70 mg. 5 week dose optimization, 3 week dose maintenance
DRUGMethylphenidate Hydrochloride
Daily oral dosing in the AM of optimized dose, ranging from 18-72 mg. 5 week dose optimization, 3 week dose maintenance
DRUGPlacebo
Daily oral dosing in the AM for 8 weeks
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
* Subject must be 13-17 years of age, inclusive, at the time of consent. * Subject must weigh more than 79.5lb. * The parent/LAR must be available at approximately 7:00AM (±2 hours) to dispense the dose of investigational product for the study duration. * Subject, who is a female, must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test and a negative urine pregnancy test and agree to comply with any applicable contraceptive requirements of the protocol. * Subject has an ADHD-RS-IV total score ≥28. * Subject is able to swallow a capsule. * Subject does not have hypertension and has a resting sitting blood pressure less than or equal to 135/85mmHg.
Exclusion criteria
* Subject has a current, controlled (with medications prohibited in this study) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any significant comorbid Axis II disorder or significant Axis I disorder (such as post traumatic stress disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, depressive or anxiety disorder. * Diagnosis of conduct disorder. Oppositional defiant disorder is not exclusionary. * Subject is considered a suicide risk, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded. * Subject is underweight or overweight. * Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition. Mild, stable asthma is not exclusionary. * Subject has a history of seizures (other than infantile febrile seizures), a chronic or current tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder. * 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 him/her at increased vulnerability to the sympathomimetic effects of a stimulant medication. * Subject has a known family history of sudden cardiac death or ventricular arrhythmia. * Subject has any clinically significant ECG or clinically significant laboratory abnormality. * Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 3 months is permitted. * Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product. * Subject has a documented allergy, hypersensitivity, or intolerance to MPH or to any excipients in the reference product. * Subject has failed to fully respond to an adequate course(s) (dose and duration) of MPH or amphetamine therapy. * Subject has a history of suspected substance abuse or dependence disorder (excluding nicotine). Subjects with a lifetime history of amphetamine, cocaine, or other stimulant abuse and/or dependence will be excluded. * Subject has a positive urine drug result. * Subject has previously participated in this study or another clinical study involving SPD489/NRP104. * Subject has glaucoma. * Subject is required to take or anticipates the need to take medications that have CNS effects or affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors. Stable use of bronchodilator inhalers is not exclusionary. * Subject is female and is pregnant or lactating. * Subject is well controlled on his/her current ADHD medication. * Subject has a pre-existing severe gastrointestinal tract narrowing.
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 Week 8 | Baseline and week 8 | 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. Higher score indicates more severe symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Improvement on Clinical Global Impression - Global Improvement (CGI-I) at Week 8 - Last Observation Carried Forward (LOCF) | Week 8 | 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. |
| Change From Baseline in Systolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment | Baseline and up to 8 Weeks | — |
| Change From Baseline in Diastolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment | Baseline and up to 8 weeks | — |
| Change From Baseline in Pulse Rate at up to 8 Weeks - Last on Treatment Assessment | Baseline and up to 8 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects received over encapsulated placebo that matched the SPD489 and OROS-MPH capsules. | 91 |
| SPD489 Subjects received over encapsulated SPD489 titrated to an optimal dose of 30, 50, or 70mg/day. | 184 |
| OROS-MPH Subjects received over encapsulated OROS-MPH titrated to an optimal dose of 18, 36, 54, or 72mg/day. Subjects optimized to 72mg received two 36mg tablets. | 184 |
| Total | 459 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 14 | 3 |
| Overall Study | Lack of Efficacy | 8 | 1 | 4 |
| Overall Study | Lost to Follow-up | 4 | 6 | 5 |
| Overall Study | Other | 2 | 0 | 6 |
| Overall Study | Protocol Violation | 0 | 4 | 4 |
| Overall Study | Withdrawal by Subject | 6 | 4 | 5 |
Baseline characteristics
| Characteristic | Placebo | SPD489 | OROS-MPH | Total |
|---|---|---|---|---|
| Age, Continuous | 14.8 Years STANDARD_DEVIATION 1.43 | 14.7 Years STANDARD_DEVIATION 1.38 | 14.7 Years STANDARD_DEVIATION 1.32 | 14.7 Years STANDARD_DEVIATION 1.37 |
| Age, Customized <=18 years | 91 Participants | 184 Participants | 184 Participants | 459 Participants |
| Region of Enrollment UNITED STATES | 91 Participants | 184 Participants | 184 Participants | 459 Participants |
| Sex: Female, Male Female | 30 Participants | 62 Participants | 62 Participants | 154 Participants |
| Sex: Female, Male Male | 61 Participants | 122 Participants | 122 Participants | 305 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 | 39 / 91 | 139 / 184 | 120 / 184 |
| serious Total, serious adverse events | 0 / 91 | 1 / 184 | 1 / 184 |
Outcome results
Primary
Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) Total Score at Week 8
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. Higher score indicates more severe symptoms.
Time frame: Baseline and week 8
Population: Full Analysis Set: All subjects who took at least 1 dose of investigational product and who had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) Total Score at Week 8 | -13.4 units on a scale | Standard Error 1.19 |
| SPD489 | Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) Total Score at Week 8 | -25.6 units on a scale | Standard Error 0.82 |
| OROS-MPH | Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) Total Score at Week 8 | -23.5 units on a scale | Standard Error 0.8 |
p-value: 0.071795% CI: [-4.3, 0.2]mixed effects model for repeated measure
p-value: <0.000195% CI: [-15.1, -9.4]mixed effects model for repeated measure
p-value: <0.000195% CI: [-13, -7.3]mixed effects model for repeated measure
Secondary
Change From Baseline in Diastolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment
Time frame: Baseline and up to 8 weeks
Population: Safety Set: All randomized subjects who took at least 1 dose of investigational product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Diastolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment | -1.2 mmHg | Standard Deviation 8.11 |
| SPD489 | Change From Baseline in Diastolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment | 2.8 mmHg | Standard Deviation 8.41 |
| OROS-MPH | Change From Baseline in Diastolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment | 2.2 mmHg | Standard Deviation 8.64 |
Secondary
Change From Baseline in Pulse Rate at up to 8 Weeks - Last on Treatment Assessment
Time frame: Baseline and up to 8 weeks
Population: Safety Set: All randomized subjects who took at least 1 dose of investigational product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pulse Rate at up to 8 Weeks - Last on Treatment Assessment | 0.3 bpm | Standard Deviation 11.32 |
| SPD489 | Change From Baseline in Pulse Rate at up to 8 Weeks - Last on Treatment Assessment | 4.7 bpm | Standard Deviation 11.82 |
| OROS-MPH | Change From Baseline in Pulse Rate at up to 8 Weeks - Last on Treatment Assessment | 6.0 bpm | Standard Deviation 10.52 |
Secondary
Change From Baseline in Systolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment
Time frame: Baseline and up to 8 Weeks
Population: Safety Set: All randomized subjects who took at least 1 dose of investigational product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment | -0.8 mmHg | Standard Deviation 8.97 |
| SPD489 | Change From Baseline in Systolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment | 2.4 mmHg | Standard Deviation 9.46 |
| OROS-MPH | Change From Baseline in Systolic Blood Pressure at up to 8 Weeks - Last on Treatment Assessment | 0.4 mmHg | Standard Deviation 9.9 |
Secondary
Percentage of Participants With Improvement on Clinical Global Impression - Global Improvement (CGI-I) at Week 8 - Last Observation Carried Forward (LOCF)
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: Week 8
Population: Full Analysis Set: All subjects who took at least 1 dose of investigational product and who had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Improvement on Clinical Global Impression - Global Improvement (CGI-I) at Week 8 - Last Observation Carried Forward (LOCF) | 34.8 percentage of participants |
| SPD489 | Percentage of Participants With Improvement on Clinical Global Impression - Global Improvement (CGI-I) at Week 8 - Last Observation Carried Forward (LOCF) | 83.1 percentage of participants |
| OROS-MPH | Percentage of Participants With Improvement on Clinical Global Impression - Global Improvement (CGI-I) at Week 8 - Last Observation Carried Forward (LOCF) | 81.0 percentage of participants |
p-value: 0.6165Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel