Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Brief summary
The study is designed to evaluate the efficacy and safety of each dose of SHP465 (12.5 and 37.5 mg) given to participants daily in the morning compared to placebo in the treatment of adults aged 18 to 55 years diagnosed with ADHD.
Interventions
DRUGSHP465 12.5mg capsules (one capsule daily)
one capsule daily
OTHERPlacebo
Matching placebo capsule that appears identical in size, weight, shape, and color (one capsule daily)
DRUGSHP465 12.5mg, 25mg, or 37.5mg capsules (one capsule daily)
One capsule daily
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Subject must be 18-55 years of age Subject is able to provide written, personally signed and dated informed consent. Subject is willing and able to comply with all of the testing and requirements defined in the protocol Subject, who is a female, must not be pregnant. Subject must have a satisfactory medical assessment with no clinically significant or relevant abnormalities. Subject has a primary diagnosis of ADHD. Subject has an adult ADHD-RS with prompts total score ≥28 at the baseline visit. Subject must have a minimum level of intellectual functioning, as determined by the investigator. Subject is able to swallow a capsule. Subject is currently not on ADHD therapy or is not completely satisfied with any aspect of their current ADHD therapy.
Exclusion criteria
Subject has a current, comorbid psychiatric diagnosis with significant symptoms. Subject is considered a suicide risk in the opinion of the investigator Subject has a body mass index (BMI) of \<18.5 kg/m2 at the screening visit. Subject has a BMI ≥40 kg/m2 at the screening visit. Subject has a concurrent chronic or acute illness, disability, or other condition. Subject has a history of seizure, a chronic or current tic disorder, or a current diagnosis of Tourette's disorder. Subject has a history of moderate to severe hypertension. Subject has a known history of symptomatic cardiovascular disease Subject has a known family history of sudden cardiac death or ventricular arrhythmia. Subject has any clinically significant ECG or clinically significant laboratory abnormality at the screening visit. Subject has current abnormal thyroid function Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product. Subject has failed to respond, to an adequate course(s) of amphetamine therapy. Subject has a history of suspected substance abuse or dependence disorder. Subject has a positive urine drug result at the screening visit (with the exception of subject's current stimulant therapy, if any) or Subject has taken another investigational product or has taken part in a clinical study within 30 days prior to the screening visit. Subject has previously completed, has discontinued, or was withdrawn from this study. Subject is taking any medication that is excluded or has not been appropriately washed out according to the protocol requirements. Subject is required to take or anticipates the need to take medications that have CNS effects or affect performance. Subject is female and is pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4) | Baseline, Visit 6 (Week 4) | The ADHD-RS was developed to measure the behaviors of children with Attention deficit hyperactivity disorder (ADHD). The adult ADHD-RS with prompts consists of 18 items designated to reflect current symptomatology of ADHD based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Each item is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), with the total score for the rating scale ranging from 0 to 54. Higher score = more severe symptoms.The scale is subdivided into 2 subscales of 9 symptoms each: hyperactivity/impulsivity and inattentiveness. Adult prompts are included with the ADHD-RS to create a semistructured measurement that allows the clinician to probe the extent, frequency, breadth, severity, and consequences of these symptoms to ascertain impairment in an adult population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Improvement (CGI-I) Score at Visit 6 (Week 4) | Visit 6 (Week 4) | CGI scales permit a global evaluation of the participant's severity and improvement over time. CGI-I was performed to rate the severity of a participant's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 43 study centers in the United States between 19 November 2015 and 24 March 2016.
Pre-assignment details
A total of 369 participants were screened and 275 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to SHP465 capsule orally once daily for 4 weeks. | 89 |
| SHP465 12.5 mg Participants received SHP465 capsule 12.5 mg orally once daily for 4 weeks. | 92 |
| SHP465 37.5 mg Participants received SHP465 capsule of 12.5 mg during week 1 and 25 mg at week 2 followed by 37.5 mg at weeks 3 and 4 orally once daily. | 90 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 7 | 5 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 | 2 |
| Overall Study | Other | 3 | 1 | 4 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 5 |
Baseline characteristics
| Characteristic | Placebo | SHP465 12.5 mg | SHP465 37.5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 34.5 Years STANDARD_DEVIATION 10.77 | 33 Years STANDARD_DEVIATION 10.4 | 32.4 Years STANDARD_DEVIATION 10.02 | 33.3 Years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 47 Participants | 35 Participants | 39 Participants | 121 Participants |
| Sex: Female, Male Male | 42 Participants | 57 Participants | 51 Participants | 150 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 | 12 / 89 | 44 / 92 | 49 / 90 |
| serious Total, serious adverse events | 0 / 89 | 0 / 92 | 0 / 90 |
Outcome results
Primary
Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4)
The ADHD-RS was developed to measure the behaviors of children with Attention deficit hyperactivity disorder (ADHD). The adult ADHD-RS with prompts consists of 18 items designated to reflect current symptomatology of ADHD based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Each item is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), with the total score for the rating scale ranging from 0 to 54. Higher score = more severe symptoms.The scale is subdivided into 2 subscales of 9 symptoms each: hyperactivity/impulsivity and inattentiveness. Adult prompts are included with the ADHD-RS to create a semistructured measurement that allows the clinician to probe the extent, frequency, breadth, severity, and consequences of these symptoms to ascertain impairment in an adult population.
Time frame: Baseline, Visit 6 (Week 4)
Population: Full Analysis Set (FAS) consisted of all participants in the safety set who had at least 1 post dose baseline primary efficacy assessment (ADHD-RS with prompt total score) on treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4) | Baseline | 40.5 Units on a scale | Standard Deviation 6.52 |
| Placebo | Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4) | Change at Visit 6 | -11.0 Units on a scale | Standard Deviation 11.47 |
| SHP465 12.5 mg | Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4) | Baseline | 39.8 Units on a scale | Standard Deviation 6.38 |
| SHP465 12.5 mg | Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4) | Change at Visit 6 | -18.1 Units on a scale | Standard Deviation 13.42 |
| SHP465 37.5 mg | Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4) | Baseline | 39.9 Units on a scale | Standard Deviation 7.07 |
| SHP465 37.5 mg | Change From Baseline in the Adult Attention-deficit/Hyperactivity Disorder Rating Scale-4 (ADHD-RS) With Prompts Total Score at Visit 6 (Week 4) | Change at Visit 6 | -23.8 Units on a scale | Standard Deviation 11.89 |
p-value: <0.00195% CI: [-11.7, -4.4]Mixed-effects model for repeated measure
p-value: <0.00195% CI: [-17.1, -9.7]Mixed-effects model for repeated measure
Secondary
Clinical Global Impression of Improvement (CGI-I) Score at Visit 6 (Week 4)
CGI scales permit a global evaluation of the participant's severity and improvement over time. CGI-I was performed to rate the severity of a participant's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time frame: Visit 6 (Week 4)
Population: Full-analysis set (FAS) consisted of all participants in the safety set who had at least 1 postdose baseline primary efficacy assessment (ADHD-RS with prompt total score) on treatment with number of participants evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Global Impression of Improvement (CGI-I) Score at Visit 6 (Week 4) | 3.1 Units on a scale | Standard Deviation 1.05 |
| SHP465 12.5 mg | Clinical Global Impression of Improvement (CGI-I) Score at Visit 6 (Week 4) | 2.4 Units on a scale | Standard Deviation 1.16 |
| SHP465 37.5 mg | Clinical Global Impression of Improvement (CGI-I) Score at Visit 6 (Week 4) | 1.9 Units on a scale | Standard Deviation 1.1 |