Safety and Efficacy of Vyvanse in Adults With Attention-Deficit/Hyperactivity Disorder

A Phase 4, Double-Blind, Multi-Center, Placebo-Controlled, Randomized Withdrawal, Safety and Efficacy Study of SPD489 in Adults Aged 18-55 With Attention-Deficit/Hyperactivity Disorder (ADHD)

The primary objective of this study is to evaluate the maintenance of efficacy, as measured by Adult ADHD Rating Scale with Prompts (Adult ADHD-RS with prompts) and Clinical Global Impression - Severity (CGI-S) scores, through a randomized withdrawal design when subjects with ADHD have been on stable treatment with commercial SPD489 for a minimum of 6 months and are maintained on their screening dose of commercial SPD489.

Study Overview

• Status: Completed
• Conditions: Attention-Deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: SPD489 (Lisdexamfetamine dimesylate); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Study Centers, LLC
  • California
    • El Centro, California, United States, 92243
      • Valley Clinical Research, Inc.
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates, Inc
    • San Diego, California, United States, 92108
      • PCSD Feighner Research
    • Wildomar, California, United States, 92595
      • Elite Clinical Trials, Inc.
  • Colorado
    • Highlands Ranch, Colorado, United States, 80130
      • Colorado Clinica Trials, Inc.
  • Florida
    • Bradenton, Florida, United States, 34208
      • Florida Clinical Research Center
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions Inc
    • Lauderhill, Florida, United States, 33319
      • Fidelity Clinical Research, Inc.
    • Orlando, Florida, United States, 32806
      • CNS Healthcare
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • West Palm Beach, Florida, United States, 33407
      • Janus Center For Psychiatric Research
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
    • Roswell, Georgia, United States, 30076
      • Northwest Behavioral Research Center
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Joliet Center for Clinical Research
    • Libertyville, Illinois, United States, 60048
      • Capstone Clinical Research
  • Kansas
    • Newton, Kansas, United States, 67114
      • CIENTIFICA, Inc
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
    • Prairie Village, Kansas, United States, 66206
      • Clinical Trial Technology Inc.
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Pedia Research LLC
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research
  • Maryland
    • Rockville, Maryland, United States, 20852
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
    • Traverse City, Michigan, United States, 49686
      • The Behavioral Medicine Clinic of NW Michigan
    • Troy, Michigan, United States, 48083
      • Behavioral Medical Center-Troy
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Midwest Research Group/ St. Charles Psychiatric Associates
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Premier Psychiatric Research Institute, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry And Behavioral Medicine Inc.
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes, LLC. Princeton Medical Institute
  • New York
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Richard H. Weisler, MD, PA & Associates
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Prarie St. Johns/ Odyssey Research
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • UHCMC/ Discovery and Wellness Center for Children
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73703
      • IPS Research Company
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Calcagno Pediatrics
  • Pennsylvania
    • Colmar, Pennsylvania, United States, 18915
      • Introspect of Buxmont, Ltd.
    • Pittsburgh, Pennsylvania, United States, 15213
      • Youth and Family Research Program
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Carolina Clinical Trials, Inc.
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare
  • Texas
    • Austin, Texas, United States, 78756
      • FutureSearch Trials
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Houston, Texas, United States, 77007
      • Bayou City Reserch, Ltd.
    • Lubbock, Texas, United States, 79423
      • Westex Clinical Investigators
    • San Antonio, Texas, United States, 78247
      • Cerebral Research, LLC
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Vermont Clinical Study Center
    • Woodstock, Vermont, United States, 05091
      • Neuropsychiatric Associates
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Psychiatric Alliance Of The Blue Ridge
    • Midlothian, Virginia, United States, 23112
      • Dominion Clinical Research
  • Washington
    • Bellevue, Washington, United States, 98004
      • Northwest Clinical Research Center
    • Kirkland, Washington, United States, 98033
      • Eastside Therapeutic Resource
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject must be 18-55 years of age, inclusive at the time of consent.
2. 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.
3. Subject has a documented diagnosis of ADHD or meets DSM-IV-TR™ with adult prompts criteria by history for a primary diagnosis of ADHD prior to treatment.
4. Subject has a Baseline score of <22 using the Adult ADHD-RS with prompts and CGI-S score ≤3.
5. Subject has been on stable treatment with commercial SPD489 (30, 50, or 70mg) for a minimum of at least 6 months preceding the Screening Visit with acceptable tolerability.Prior treatment with commercial SPD489 in the 6 months preceding the Screening Visit must be documented by prescription records, prescribing physician notes, or pharmacy records. Those subjects whose primary care physician (PCP) is someone other than the Principal Investigator (PI) will be required to provide the above documentation to the site.
6. Subject must have a minimum level of intellectual functioning, as determined by the Investigator.
7. Subject is willing and able to comply with all the testing and requirements defined in this protocol.
8. Subject is able to swallow a capsule.
9. Subject must be able to provide written, personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E627 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. Subject is currently considered a suicide risk, has previously made a suicide attempt or has a prior history of, or is currently demonstrating 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, or 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.
9. Subject has current abnormal thyroid function, as 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.
11. Subject is taking any medication that is excluded (Please refer to Table 2).
12. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamines.
13. 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.
14. Subject has a positive urine drug result at Screening (with the exception of subject's current stimulant therapy).
15. Subject has taken an investigational compound that has a central nervous system(CNS) effect or taken part in a clinical trial for ADHD 6 months prior to the Screening Visit.
16. Subject has taken part in an investigational trial within the 30 days prior to the Screening Visit.
17. Subject has glaucoma.
18. Subject is taking other medications that have CNS effects or affect performance, such as chronic use of sedating antihistamines and decongestant sympathomimetics (7 days prior to Screening). Stable use of bronchodilator inhalers is not exclusionary.
19. Subject is female and pregnant or lactating.
20. Subjects who have previously been enrolled into this study and subsequently withdrawn.
21. Subject is not well controlled on SPD489 with acceptable tolerability (Adult ADHD-RS with prompts score ≥22).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 1 capsule (identical to drug capsules) per day for 4 weeks during the double blind period.
Experimental: SPD489	Drug: SPD489 (Lisdexamfetamine dimesylate); 1 capsule (either 30, 50, or 70mg strength) per day for 6 weeks.; Other Names: Vyvanse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Treatment Failures at up to 6 Weeks	Treatment failure defined as > or equal to 50% increase in the ADHD-RS with adult prompts total score and a > or equal to 2 point increase in the CGI-S score.	Up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) With Adult Prompts Total Score at up to 6 Weeks	The 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.	Up to 6 weeks
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at up to 6 Weeks	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)	Up to 6 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Brams M, Weisler R, Findling RL, Gasior M, Hamdani M, Ferreira-Cornwell MC, Squires L. Maintenance of efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: randomized withdrawal design. J Clin Psychiatry. 2012 Jul;73(7):977-83. doi: 10.4088/JCP.11m07430. Epub 2012 Jun 12.
• Weisler RH, Babcock T, Adeyi B, Brams M. Relationship of ADHD symptoms and global illness severity in adults treated with lisdexamfetamine dimesylate. Postgrad Med. 2014 Sep;126(5):31-41. doi: 10.3810/pgm.2014.09.2798.

Helpful Links

• FDA Recall Information
• FDA Approved Label

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2009
• Primary Completion (Actual): July 8, 2010
• Study Completion (Actual): July 8, 2010

Study Registration Dates

• First Submitted: March 19, 2009
• First Submitted That Met QC Criteria: April 6, 2009
• First Posted (Estimate): April 7, 2009

Study Record Updates

• Last Update Posted (Actual): June 22, 2021
• Last Update Submitted That Met QC Criteria: June 9, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: ADHD
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: SPD489-401