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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00697515
First received: June 11, 2008
Last updated: December 6, 2011
Last verified: December 2011
  Purpose

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


Condition Intervention Phase
ADHD
Drug: LDX
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Permanent Product Measure of Performance (PERMP) Total Score Over the Treatment Day in the Crossover Phase [ Time Frame: 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7, 14, 21 and 28 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7, 14, 21 and 28 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 26 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 26 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 26 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 26 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 7, 14, 21 and 28 days ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Electrocardiogram Results (QTcF Interval) at 7 Days in the Crossover Phase [ Time Frame: Baseline and 7 days ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 142
Study Start Date: July 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: Placebo Drug: Placebo
Placebo administered once-daily for one week during the adult workplace environment setting

Detailed Description:

This study has both an optimization and double-blind period

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697515

Locations
United States, Arkansas
Clinical Study Centers, LLC
Little Rock, Arkansas, United States, 72205
United States, California
University of CA, Irvine Child Development Center
Irvine, California, United States, 92612
United States, Kansas
Vince & Associates Clinical Research
Overland Park, Kansas, United States, 66212
United States, Nevada
Center for Psychiatry & Behavioral Medicine, Inc
Las Vegas, Nevada, United States, 89128
United States, Texas
Bayou City Research, LTD
Houston, Texas, United States, 77007
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Tim Wigal, PhD University of CA, Irvine Child Development Center
  More Information

Additional Information:
Publications:
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. Wigal T, Brams M, Gasior M, et al. Behavioral and Brain Functions, 2010; 6:34
Brown TE, Brams M, Gasior M, et al. Clinical utility of ADHD symptom thresholds to assess normalization of executive function with lisdexamfetamine dimesylate treatment in adults. Current Medical Research & Opinion 2011;27(S2):23-33.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00697515     History of Changes
Other Study ID Numbers: SPD489-316
Study First Received: June 11, 2008
Results First Received: November 20, 2009
Last Updated: December 6, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Dyskinesias
Mental Disorders
Mental Disorders Diagnosed in Childhood
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Dextroamphetamine
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014