Clinical trial NCT01101022: Safety and Efficacy of SPD489 on Executive Function Behaviors in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
Official title: A Phase 4, Randomized, Double-Blind, Multicenter, Placebo-controlled, Parallel Group Study Evaluating the Safety and Efficacy of SPD489 on Executive Function (Self-Regulation) Behaviors in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD) Reporting Clinically Significant Impairment of Real-World Executive Function Behavior.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: ADHD Specifically With Executive Function Impairment
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-04-09
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the efficacy of SPD489 compared to placebo on executive function (self-regulation) behaviors in adults with ADHD who report clinically significant impairment of executive function behavior in their everyday environment, as measured by the self-report Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Global Executive Composite (GEC) T-score.


Eligibility criteria: Inclusion Criteria:

1. Subject must be 18-55 years of age, inclusive at the time of consent.
2. Subject has an established close relationship of at least 6-months duration before screening (Visit -1) with an informant who will be able to observe and be willing to report on the subject's behavior and symptoms in multiple social settings during the course of the study. Informant is defined as a person who has a domicile relationship with the subject. When applicable, the informant should be the subject's spouse/significant other. Additionally, the informant cannot participate as a subject in the study and can only serve as the informant for a single subject.
3. Subject has a lifestyle that in the opinion of the Investigator will enable the subject to complete all study testing and requirements defined in the protocol.
4. Female subjects must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test at screening (Visit -1) and a negative urine pregnancy test at baseline (Visit 0) and agree to comply with any applicable contraceptive requirements of the protocol.
5. Subject meets the 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.
6. Subject has a total score of ≥65 on BRIEF-A GEC T-score by self-report at baseline (Visit 0).
7. Subject has a total score of ≥28 using the Adult ADHD-RS with prompts at baseline (Visit 0).
8. Subject must have a minimum level of intellectual functioning as determined by the Investigator at screening (Visit -1).
9. Subject is able to swallow a capsule.
10. Subject is willing and able to comply with all the testing and requirements defined in this protocol.
11. Subject and informant must be able to provide written, personally signed and dated informed consent to participate in the study in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines and applicable regulations before completing any study related procedures.

Exclusion Criteria

1. 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. Prohibited disorders include those associated with diagnoses including but not limited to any severe comorbid Axis II disorder or severe Axis I disorder (such as Post Traumatic Stress Disorder \[PTSD\], psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder). Other symptomatic manifestations (such as agitated states) that contraindicate treatment with SPD489 or confound efficacy or safety assessments in the opinion of the examining physician are also prohibited. Comorbid psychiatric diagnoses will be established by the psychiatric evaluation that includes the Structured Clinical Interview for DSM-IV-TR disorders (SCID-I).
2. 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.
3. The subject has a body mass index (BMI) of \<18.5 or ≥40.
4. Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments administered in the study or that might increase risk to the subject. Similarly, the subject will be excluded if he or she has any additional condition(s) that in the Investigator's opinion would prohibit the subject from completing the study or would not be in the best interest of the subject. This would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol. Mild, stable asthma is not exclusionary.
5. Subject has a history of seizures (other than infantile febrile seizures), any tic disorder, a current diagnosis and/or a known family history of Tourette's Disorder.
6. 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.
7. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
8. Subject has any clinically significant ECG or clinically significant laboratory abnormality at screening (Visit -1).
9. Subject has current abnormal thyroid function, defined as abnormal screening thyroid stimulating hormone (TSH) and thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
10. Subject has a history of moderate to severe hypertension or has a resting sitting systolic blood pressure \>139mmHg or diastolic blood pressure \>89mmHg. Subjects with well-controlled mild or moderate hypertension on a single antihypertensive agent are allowed. Combination antihypertensive medications are not allowed.
11. Subject is taking any medication that is excluded.
12. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamines.
13. Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the investigational medicinal product.
14. Subject has failed to respond to one or more adequate courses (dose and duration) of amphetamine therapy.
15. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-IV-TR criteria.
16. Subject has a positive urine drug result at screening (Visit -1) (with the exception of subject's current stimulant therapy, if any).
17. Subject has taken an investigational drug or taken part in a clinical trial, including an SPD489 clinical trial, within 30 days prior to screening (Visit -1).
18. Subject has glaucoma.
19. 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 7 days of investigational medicinal product administration). Stable use of bronchodilator inhalers is not exclusionary.
20. Subject is female and pregnant or lactating.
21. Subjects who have previously been randomized into this study and subsequently withdrawn.
22. Subject is well controlled on their current ADHD medication with acceptable tolerability.

Primary outcomes:
measure: Change From Baseline in Subject-reported Behavior Rating Inventory of Executive Function - Adult Version Global Executive Composite T-score (BRIEF-A GEC T) at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
Secondary outcomes:
measure: Change From Baseline in Adult ADHD Impact Module (AIM-A) Multi-Item Scales Total Score at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Change From Baseline in Informant-reported BRIEF-A T-scores at up to 10 Weeks
timeFrame: Baseline and up to10 weeks
measure: Change From Baseline in Subject-reported BRIEF-A T-scores at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Change From Baseline in Subject-reported BRIEF-A Clinical Subscales T-scores at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Change From Baseline in Informant-reported BRIEF-A Clinical Subscales T-scores at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) With Adult Prompts Total Score at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Baseline
timeFrame: Baseline
measure: Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at up to 10 Weeks
timeFrame: Up to 10 weeks post-dose
measure: Percent of Participants With Improvement on Clinical Global Impression - Global Improvement (CGI-I) at up to 10 Weeks
timeFrame: Up to 10 weeks post-dose
measure: Change From Baseline in AIM-A Multi-Item Scales of Living With ADHD and General Well-being Score at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Change From Baseline in AIM-A Quality of Life Questions 1 and 4 Scores at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Change From Baseline in Conner's Adult ADHD Rating Scale-Observer: Short Version (CAARS-O:S) ADHD Index T-score at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Change From Baseline in CAARS-O:S Factor-derived Subscale T-scores at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
measure: Change From Baseline in Adult ADHD Quality of Life (AAQoL) Scale Total Score at up to 10 Weeks
timeFrame: Baseline and up to 10 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Clinical Study Centers, LLC
state: Arkansas
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Assoc, Inc
state: California
city: San Diego
country: United States
facility: PCSD Feighner Research
state: California
city: Bradenton
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Fort Myers
country: United States
facility: Gulfcoast Clinical Research Center
state: Florida
city: Jacksonville Beach
country: United States
facility: Dr. George Joseph, MD and Associates PA
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Orlando
country: United States
facility: CNS Healthcare
state: Florida
city: West Palm Beach
country: United States
facility: Janus Center For Psychiatric Research
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center For Medical Research
state: Georgia
city: Marietta
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Libertyville
country: United States
facility: Capstone Clinical Research
state: Illinois
city: Naperville
country: United States
facility: AMR-BABER Research Inc.
state: Illinois
city: Overland Park
country: United States
facility: Psychiatric Associates
state: Kansas
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research, Inc.
state: Kansas
city: Paducah
country: United States
facility: Four Rivers Clinical Research
state: Kentucky
city: Rockville
country: United States
facility: Mark Hertzman MD, PC
state: Maryland
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: Traverse City
country: United States
facility: The Behavioral Medicine Clinic of NW Michigan, PC
state: Michigan
city: Saint Charles
country: United States
facility: Midwest Research Group
state: Missouri
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine, Inc.
state: Nevada
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Mount Kisco
country: United States
facility: Bioscience Research, LLC
state: New York
city: New York
country: United States
facility: Mental Health and Addictive Disorders Research Program
state: New York
city: Durham
country: United States
facility: Triangle Neuropsychiatry
state: North Carolina
city: Raleigh
country: United States
facility: Richard H. Weisler, MD, Pa & Associates
state: North Carolina
city: Portland
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Salem
country: United States
facility: Occi, Inc (Oregon Center For Clinical Investigations, Inc.)
state: Oregon
city: Austin
country: United States
facility: FutureSearch Trials, LP
state: Texas
city: Houston
country: United States
facility: Bayou City Research, Ltd.
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates P.A.
state: Texas
city: Lubbock
country: United States
facility: John M. Turnbow, MD, PA
state: Texas
city: Burlington
country: United States
facility: Vermont Clinical Study Center
state: Vermont
city: Woodstock
country: United States
facility: Neuropsychiatric Associates
state: Vermont
city: Herndon
country: United States
facility: Neuroscience, Inc
state: Virginia
city: Kirkland
country: United States
facility: Eastside Therapeutic Resource
state: Washington
city: Seattle
country: United States
facility: Summit Research Network, LLC
state: Washington
city: Spokane
country: United States
facility: Rockwood Clinic
state: Washington
city: Middleton
country: United States
facility: Dean Foundation for Health, Research and Education
state: Wisconsin
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Adler LA, Dirks B, Deas PF, Raychaudhuri A, Dauphin MR, Lasser RA, Weisler RH. Lisdexamfetamine dimesylate in adults with attention-deficit/ hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013 Jul;74(7):694-702. doi: 10.4088/JCP.12m08144.
citation: Brown TE, Chen J, Robertson B. Relationships Between Executive Function Improvement and ADHD Symptom Improvement With Lisdexamfetamine Dimesylate in Adults With ADHD and Executive Function Deficits: A Post Hoc Analysis. Prim Care Companion CNS Disord. 2020 May 28;22(3):19m02559. doi: 10.4088/PCC.19m02559.
citation: Adler LA, Dirks B, Deas P, Raychaudhuri A, Dauphin M, Saylor K, Weisler R. Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study. BMC Psychiatry. 2013 Oct 9;13:253. doi: 10.1186/1471-244X-13-253.