Back to resultsSafety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)
Primary Purpose
ADHD
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
LDX
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for ADHD
Eligibility Criteria
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.
Sites / Locations
- Clinical Study Centers, LLC
- University of CA, Irvine Child Development Center
- Vince & Associates Clinical Research
- Center for Psychiatry & Behavioral Medicine, Inc
- Bayou City Research, LTD
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Lisdexamfetamine Dimesylate (LDX, SPD489)
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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)
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.
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.
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.
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.
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).
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).
Change From Baseline in Systolic Blood Pressure at Up to 28 Days in the Dose Optimization Phase
Change From Baseline in Diastolic Blood Pressure at Up to 28 Days in the Dose Optimization Phase
Change From Baseline in Pulse Rate at Up to 28 Days in the Dose Optimization Phase
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00697515
Brief Title
Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
July 18, 2008 (Actual)
Primary Completion Date
December 20, 2008 (Actual)
Study Completion Date
December 20, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate the efficacy of LDX compared to placebo in adults with ADHD in the adult workplace environment (AWE) setting
Detailed Description
This study has both an optimization and double-blind period
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ADHD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
142 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lisdexamfetamine Dimesylate (LDX, SPD489)
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
LDX
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo administered once-daily for one week during the adult workplace environment setting
Primary Outcome Measure Information:
Title
Permanent Product Measure of Performance (PERMP) Total Score Over the Treatment Day in the Crossover Phase
Description
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.
Time Frame
2, 4, 8, 10, 12 and 14 hours post-dose on Day 7
Secondary Outcome Measure Information:
Title
PERMP Total Score by Timepoint in the Crossover Phase
Description
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.
Time Frame
2, 4, 8, 10, 12 and 14 hours post-dose on Day 7
Title
PERMP Score for the Number of Math Problems Attempted by Timepoint in the Crossover Phase
Description
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.
Time Frame
2, 4, 8, 10, 12 and 14 hours post-dose on Day 7
Title
PERMP Score for the Number of Math Problems Answered Correctly by Timepoint in the Crossover Phase
Description
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.
Time Frame
2, 4, 8, 10, 12 and 14 hours post-dose on Day 7
Title
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
Description
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.
Time Frame
Baseline and 7, 14, 21 and 28 days
Title
ADHD-RS With Prompts Total Score in the Crossover Phase
Description
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.
Time Frame
7 days
Title
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) in the Dose Optimization Phase
Description
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)
Time Frame
Baseline
Title
Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) in the Dose Optimization Phase
Description
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
7, 14, 21 and 28 days
Title
Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) in the Crossover Phase
Description
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
7 days
Title
Change From Baseline in the Brown Attention Deficit Disorder Scale (BADDS) Total Scores at 26 Days in the Dose Optimization Phase
Description
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.
Time Frame
Baseline and 26 days
Title
Level of Satisfaction With Study Treatment on Medication Satisfaction Questionnaire (MSQ) in the Dose Optimization Phase
Description
MSQ is a survey rating the subject's level of satisfaction with the study treatment medication.
Time Frame
26 days
Title
Change From Baseline in Adult ADHD Impact Module (AIM-A) Question 1 Score at 26 Days in the Dose Optimization Phase
Description
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).
Time Frame
Baseline and 26 days
Title
Change From Baseline in AIM-A Question 4 Score at 26 Days in the Dose Optimization Phase
Description
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).
Time Frame
Baseline and 26 days
Title
Change From Baseline in Systolic Blood Pressure at Up to 28 Days in the Dose Optimization Phase
Time Frame
Baseline and 7, 14, 21 and 28 days
Title
Change From Baseline in Diastolic Blood Pressure at Up to 28 Days in the Dose Optimization Phase
Time Frame
Baseline and 7, 14, 21 and 28 days
Title
Change From Baseline in Pulse Rate at Up to 28 Days in the Dose Optimization Phase
Time Frame
Baseline and 7, 14, 21 and 28 days
Title
Change From Baseline in Electrocardiogram Results (QTcF Interval) at 7 Days in the Crossover Phase
Description
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.
Time Frame
Baseline and 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Study Centers, LLC
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of CA, Irvine Child Development Center
City
Irvine
State/Province
California
ZIP/Postal Code
92612
Country
United States
Facility Name
Vince & Associates Clinical Research
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
Facility Name
Center for Psychiatry & Behavioral Medicine, Inc
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Bayou City Research, LTD
City
Houston
State/Province
Texas
ZIP/Postal Code
77007
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20576091
Citation
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.
Results Reference
result
PubMed Identifier
21566420
Citation
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.
Results Reference
result
PubMed Identifier
21973229
Citation
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.
Results Reference
result
PubMed Identifier
20861583
Citation
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.
Results Reference
derived
Links:
URL
http://www.fda.gov/opacom/7alerts.html
Description
FDA recall information
URL
http://www.vyvanse.com/pdf/prescribing_information.pdf
Description
FDA-approved label
Learn more about this trial
Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)
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