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

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)

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

Study Overview

• Status: Completed
• Conditions: ADHD
• Intervention / Treatment: Drug: LDX; Drug: Placebo

Detailed Description

This study has both an optimization and double-blind period

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Study Centers, LLC
  • California
    • Irvine, California, United States, 92612
      • University of CA, Irvine Child Development Center
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince & Associates Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry & Behavioral Medicine, Inc
  • Texas
    • Houston, Texas, United States, 77007
      • Bayou City Research, Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo administered once-daily for one week during the adult workplace environment setting
ACTIVE_COMPARATOR: Lisdexamfetamine Dimesylate (LDX, SPD489)	Drug: LDX; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Wigal T, Brams M, Gasior M, Gao J, Squires L, Giblin J; 316 Study Group. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design. Behav Brain Funct. 2010 Jun 24;6:34. doi: 10.1186/1744-9081-6-34.
• Brams M, Giblin J, Gasior M, Gao J, Wigal T. Effects of open-label lisdexamfetamine dimesylate on self-reported quality of life in adults with ADHD. Postgrad Med. 2011 May;123(3):99-108. doi: 10.3810/pgm.2011.05.2288.
• Brown TE, Brams M, Gasior M, Adeyi B, Babcock T, Dirks B, Scheckner B, Wigal T. Clinical utility of ADHD symptom thresholds to assess normalization of executive function with lisdexamfetamine dimesylate treatment in adults. Curr Med Res Opin. 2011;27 Suppl 2:23-33. doi: 10.1185/03007995.2011.605441.
• Brown TE, Brams M, Gao J, Gasior M, Childress A. Open-label administration of lisdexamfetamine dimesylate improves executive function impairments and symptoms of attention-deficit/hyperactivity disorder in adults. Postgrad Med. 2010 Sep;122(5):7-17. doi: 10.3810/pgm.2010.09.2196.

Helpful Links

• FDA Recall Information
• FDA-approved Label

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2008
• Primary Completion (ACTUAL): December 20, 2008
• Study Completion (ACTUAL): December 20, 2008

Study Registration Dates

• First Submitted: June 11, 2008
• First Submitted That Met QC Criteria: June 13, 2008
• First Posted (ESTIMATE): June 16, 2008

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity
• Other Study ID Numbers: SPD489-316