Safety and Efficacy Study of SHP465 in Adults Aged 18-55 Years With Attention-deficit/ Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Randomized, Double-blind, Multicenter, Placebo-controlled, Forced-dose Titration, Safety and Efficacy Study of SHP465 in Adults Aged 18-55 Years With Attention-deficit/ Hyperactivity Disorder (ADHD)

Conditions
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Attention Deficit Hyperactivity Disorder (ADHD)

Intervention / Treatment
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* Drug: SHP465 12.5mg capsules (one capsule daily)
* Other: Placebo
* Drug: SHP465 12.5mg, 25mg, or 37.5mg capsules (one capsule daily)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHP465 12.5 mg<br>Subjects will receive SHP465 12.5 mg | Drug: SHP465 12.5mg capsules (one capsule daily)<br>* one capsule daily<br>|
| Experimental: SHP465 37.5 mg<br>Subjects will receive SHP465 titrated up to 37.5 mg | Drug: SHP465 12.5mg, 25mg, or 37.5mg capsules (one capsule daily)<br>* One capsule daily<br>|
| Placebo Comparator: Placebo<br>Subjects will receive matching placebo | Other: Placebo<br>* Matching placebo capsule that appears identical in size, weight, shape, and color (one capsule daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Visit 6 (Week 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Visit 6 (Week 4) |