Safety and Efficacy of SPD489 on Executive Function Behaviors in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)

NCT ID: NCT01101022

Last Updated: 2021-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-19
• Study Completion Date: 2010-11-29

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.

Conditions

ADHD Specifically With Executive Function Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

SPD489

Group Type: ACTIVE_COMPARATOR

SPD489

Intervention Type: DRUG

1 capsule per day (30, 50 or 70 mg), daily throughout the double-blind treatment period (10 weeks)

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

1 capsule per day, daily throughout the double-blind treatment period (10 weeks)

Interventions

SPD489

1 capsule per day (30, 50 or 70 mg), daily throughout the double-blind treatment period (10 weeks)

Intervention Type: DRUG

Placebo

1 capsule per day, daily throughout the double-blind treatment period (10 weeks)

Intervention Type: OTHER

Other Intervention Names

Vyvanse

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Clinical Study Centers, LLC

Little Rock, Arkansas, United States

Peninsula Research Assoc, Inc

Rolling Hills Estates, California, United States

PCSD Feighner Research

San Diego, California, United States

Florida Clinical Research Center, LLC

Bradenton, Florida, United States

Gulfcoast Clinical Research Center

Fort Myers, Florida, United States

Dr. George Joseph, MD and Associates PA

Jacksonville Beach, Florida, United States

Florida Clinical Research Center, LLC

Maitland, Florida, United States

CNS Healthcare

Orlando, Florida, United States

Janus Center For Psychiatric Research

West Palm Beach, Florida, United States

Atlanta Center For Medical Research

Atlanta, Georgia, United States

Northwest Behavioral Research Center

Marietta, Georgia, United States

Capstone Clinical Research

Libertyville, Illinois, United States

AMR-BABER Research Inc.

Naperville, Illinois, United States

Psychiatric Associates

Overland Park, Kansas, United States

Vince and Associates Clinical Research, Inc.

Overland Park, Kansas, United States

Four Rivers Clinical Research

Paducah, Kentucky, United States

Mark Hertzman MD, PC

Rockville, Maryland, United States

Rochester Center for Behavioral Medicine

Rochester Hills, Michigan, United States

The Behavioral Medicine Clinic of NW Michigan, PC

Traverse City, Michigan, United States

Midwest Research Group

Saint Charles, Missouri, United States

Center for Psychiatry and Behavioral Medicine, Inc.

Las Vegas, Nevada, United States

Center for Emotional Fitness

Cherry Hill, New Jersey, United States

Bioscience Research, LLC

Mount Kisco, New York, United States

Mental Health and Addictive Disorders Research Program

New York, New York, United States

Triangle Neuropsychiatry

Durham, North Carolina, United States

Richard H. Weisler, MD, Pa & Associates

Raleigh, North Carolina, United States

Oregon Center for Clinical Investigations, Inc.

Portland, Oregon, United States

Occi, Inc (Oregon Center For Clinical Investigations, Inc.)

Salem, Oregon, United States

FutureSearch Trials, LP

Austin, Texas, United States

Bayou City Research, Ltd.

Houston, Texas, United States

Red Oak Psychiatry Associates P.A.

Houston, Texas, United States

John M. Turnbow, MD, PA

Lubbock, Texas, United States

Vermont Clinical Study Center

Burlington, Vermont, United States

Neuropsychiatric Associates

Woodstock, Vermont, United States

Neuroscience, Inc

Herndon, Virginia, United States

Eastside Therapeutic Resource

Kirkland, Washington, United States

Summit Research Network, LLC

Seattle, Washington, United States

Rockwood Clinic

Spokane, Washington, United States

Dean Foundation for Health, Research and Education

Middleton, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 23945447 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32470230 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24106804 (View on PubMed)

Other Identifiers

SPD489-403

Identifier Type: -

Identifier Source: org_study_id