Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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To evaluate the efficacy of LDX compared to placebo in adults with ADHD in the adult workplace environment (AWE) setting

Detailed Description
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This study has both an optimization and double-blind period

Official Title
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A Phase IIIb Randomized, Double-Blind, Multicenter, Placebo-Controlled, Dose Optimization, Crossover, Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

Conditions
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ADHD

Intervention / Treatment
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* Drug: LDX
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be 18-55 years of age, inclusive at the time of consent. Female subjects must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to comply with any applicable contraceptive requirements of the protocol. Subject meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition; Text Revision (DSM IV TR) criteria for a primary diagnosis of ADHD (diagnostic code 314.00 and 314.01) established by a comprehensive psychiatric evaluation that reviews DSM-IV-TR criteria with at least 6 of the 9 subtype criteria met. The Adult ADHD Clinical Diagnostic Scale version 1.2 (ACDS v1.2) will be utilized as the diagnostic tool. Subject has a Baseline score of > or equal to 28 using the Adult ADHD-RS with prompts. Subject must have a minimum level of intellectual functioning, as determined by an Intelligent Quotient (IQ) score of 80 or above based on the Kaufman Brief Intelligence Test (KBIT). Exclusion Criteria: Subject has a current comorbid psychiatric disorder that is either controlled with medications prohibited in this study or is uncontrolled and associated with significant symptoms. Comorbid psychiatric diagnoses will be established by the psychiatric evaluation that includes the Structured Clinical Interview for DSM-IV-TR disorders (SCID-I). Subjects who are currently considered a suicide risk, any subject who has previously made a suicide attempt or those who are currently demonstrating active suicidal ideation. Subject has a history of seizures (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder. Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug. Subject has current abnormal thyroid function, as defined as abnormal Screening thyroid stimulating hormone. Treatment with a stable dose of thyroid medication for at least 3 months is permitted. Subject has a history of moderate to severe hypertension or has a resting sitting systolic blood pressure >139mmHg or diastolic blood pressure >89mmHg. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamines. Subject has failed to respond to one or more adequate courses (dose and duration) of amphetamine therapy. Subject has glaucoma. Subject is taking other medications that have central nervous system (CNS) effects or affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors (during or within 14 days of test or reference product administration). Stable use of bronchodilator inhalers is not exclusionary. Subject is female and 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lisdexamfetamine Dimesylate (LDX, SPD489)<br> | Drug: LDX<br>* oral, 30, 50, or 70 mg once-daily for 4 weeks during dose optimization, and then for 1 week during each crossover during the adult workplace environment setting<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo administered once-daily for one week during the adult workplace environment setting<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Permanent Product Measure of Performance (PERMP) Total Score Over the Treatment Day in the Crossover Phase | The Permanent Product Measure of Performance (PERMP) is a skill adjusted math test. The PERMP score is the sum of the number of math problems attempted plus the number of math problems answered correctly in a 10-minute session. The scores range from 0-800 with higher scores indicating better performance. | 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PERMP Total Score by Timepoint in the Crossover Phase | The Permanent Product Measure of Performance (PERMP) is a skill adjusted math test. The PERMP score is the sum of the number of math problems attempted plus the number of math problems answered correctly in a 10-minute session. The scores range from 0-800 with higher scores indicating better performance. | 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7 | 
| PERMP Score for the Number of Math Problems Attempted by Timepoint in the Crossover Phase | The Permanent Product Measure of Performance (PERMP) is a skill adjusted math test. The PERMP score is the sum of the number of math problems attempted plus the number of math problems answered correctly in a 10-minute session. The scores range from 0-800 with higher scores indicating better performance. | 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7 | 
| PERMP Score for the Number of Math Problems Answered Correctly by Timepoint in the Crossover Phase | The Permanent Product Measure of Performance (PERMP) is a skill adjusted math test. The PERMP score is the sum of the number of math problems attempted plus the number of math problems answered correctly in a 10-minute session. The scores range from 0-800 with higher scores indicating better performance. | 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7 | 
| Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale With Prompts (ADHD-RS) Total Score at up to 28 Days in the Dose Optimization Phase | The Attention Deficit Hyperactivity Disorder Rating Scale with Prompts (ADHD-RS) 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. | Baseline and 7, 14, 21 and 28 days | 
| ADHD-RS With Prompts Total Score in the Crossover Phase | The Attention Deficit Hyperactivity Disorder Rating Scale with Prompts (ADHD-RS) 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. | 7 days | 
| Assessment of Clinical Global Impression-Severity of Illness (CGI-S) in the Dose Optimization Phase | 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) | Baseline | 
| Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) in the Dose Optimization Phase | 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. | 7, 14, 21 and 28 days | 
| Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) in the Crossover Phase | 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. | 7 days | 
| Change From Baseline in the Brown Attention Deficit Disorder Scale (BADDS) Total Scores at 26 Days in the Dose Optimization Phase | The BADDS assessment consists of 40 items rated on a scale from 0 (never) to 3 (almost daily). The total score ranges from 0 to 120 with increasing scores indicating more severe impairment. | Baseline and 26 days | 
| Level of Satisfaction With Study Treatment on Medication Satisfaction Questionnaire (MSQ) in the Dose Optimization Phase | MSQ is a survey rating the subject's level of satisfaction with the study treatment medication. | 26 days | 
| Change From Baseline in Adult ADHD Impact Module (AIM-A) Question 1 Score at 26 Days in the Dose Optimization Phase | AIM-A is a quality of life instrument. Question 1 is 'On a scale of 1 to 10, how would you rate the overall quality of life right now?' It is rated on a scale of 1 (worst) to 10 (best). | Baseline and 26 days | 
| Change From Baseline in AIM-A Question 4 Score at 26 Days in the Dose Optimization Phase | AIM-A is a quality of life instrument. Question 4 is 'How much do you agree with this statement: Over the past few weeks, I've had more good days than bad days?' This is rated on a scale of 1 (strongly agree) to 5 (strongly disagree). | Baseline and 26 days | 
| Change From Baseline in Systolic Blood Pressure at Up to 28 Days in the Dose Optimization Phase |  | Baseline and 7, 14, 21 and 28 days | 
| Change From Baseline in Diastolic Blood Pressure at Up to 28 Days in the Dose Optimization Phase |  | Baseline and 7, 14, 21 and 28 days | 
| Change From Baseline in Pulse Rate at Up to 28 Days in the Dose Optimization Phase |  | Baseline and 7, 14, 21 and 28 days | 
| Change From Baseline in Electrocardiogram Results (QTcF Interval) at 7 Days in the Crossover Phase | QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate(e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation. | Baseline and 7 days |