Clinical trial NCT00697515: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: ADHD
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-06-16
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Permanent Product Measure of Performance (PERMP) Total Score Over the Treatment Day in the Crossover Phase
timeFrame: 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7
Secondary outcomes:
measure: PERMP Total Score by Timepoint in the Crossover Phase
timeFrame: 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7
measure: PERMP Score for the Number of Math Problems Attempted by Timepoint in the Crossover Phase
timeFrame: 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7
measure: PERMP Score for the Number of Math Problems Answered Correctly by Timepoint in the Crossover Phase
timeFrame: 2, 4, 8, 10, 12 and 14 hours post-dose on Day 7
measure: 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
timeFrame: Baseline and 7, 14, 21 and 28 days
measure: ADHD-RS With Prompts Total Score in the Crossover Phase
timeFrame: 7 days
measure: Assessment of Clinical Global Impression-Severity of Illness (CGI-S) in the Dose Optimization Phase
timeFrame: Baseline
measure: Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) in the Dose Optimization Phase
timeFrame: 7, 14, 21 and 28 days
measure: Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) in the Crossover Phase
timeFrame: 7 days
measure: Change From Baseline in the Brown Attention Deficit Disorder Scale (BADDS) Total Scores at 26 Days in the Dose Optimization Phase
timeFrame: Baseline and 26 days
measure: Level of Satisfaction With Study Treatment on Medication Satisfaction Questionnaire (MSQ) in the Dose Optimization Phase
timeFrame: 26 days
measure: Change From Baseline in Adult ADHD Impact Module (AIM-A) Question 1 Score at 26 Days in the Dose Optimization Phase
timeFrame: Baseline and 26 days
measure: Change From Baseline in AIM-A Question 4 Score at 26 Days in the Dose Optimization Phase
timeFrame: Baseline and 26 days
measure: Change From Baseline in Systolic Blood Pressure at Up to 28 Days in the Dose Optimization Phase
timeFrame: Baseline and 7, 14, 21 and 28 days
measure: Change From Baseline in Diastolic Blood Pressure at Up to 28 Days in the Dose Optimization Phase
timeFrame: Baseline and 7, 14, 21 and 28 days
measure: Change From Baseline in Pulse Rate at Up to 28 Days in the Dose Optimization Phase
timeFrame: Baseline and 7, 14, 21 and 28 days
measure: Change From Baseline in Electrocardiogram Results (QTcF Interval) at 7 Days in the Crossover Phase
timeFrame: Baseline and 7 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Clinical Study Centers, LLC
state: Arkansas
city: Irvine
country: United States
facility: University of CA, Irvine Child Development Center
state: California
city: Overland Park
country: United States
facility: Vince & Associates Clinical Research
state: Kansas
city: Las Vegas
country: United States
facility: Center for Psychiatry & Behavioral Medicine, Inc
state: Nevada
city: Houston
country: United States
facility: Bayou City Research, LTD
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.