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Triple-Bead Mixed Amphetamine Salts (SPD465), a Novel, Enhanced Extended-Release Amphetamine Formulation for the Treatment of Adults With ADHD: A Randomized, Double-Blind, Multicenter, Placebo-Controlled StudyThomas J. Spencer, M.D.; Lenard A. Adler, M.D.; Richard H. Weisler, M.D.; and Sharon H. Youcha, M.D.Introduction: The efficacy and safety of triple-bead mixed amphetamine salts (MAS), an oral, once-daily, enhanced extended-release amphetamine formulation designed for a duration of action up to 16 hours, were evaluated in adults with attention-deficit/hyperactivity disorder (ADHD). Method: In this phase 3, 7-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, dose-optimization study of 272 adults with ADHD (DSM-IV-TR criteria), subjects (aged 18 to 55 years) were randomly assigned to triple-bead MAS (starting dose 12.5 mg) or placebo. The primary outcome measure was change in ADHD Rating Scale-IV (ADHD-RS-IV). Secondary outcome measures included Clinical Global Impressions (CGI) scale, Time-Sensitive ADHD Symptom Scale (TASS) (measuring extended duration), Brown Attention-Deficit Disorder Scale (BADDS) (measuring executive function), Adult ADHD Impact Module (AIM-A) (measuring quality of life [QOL]), and ADHD-RS-IV hyperactivity-impulsivity and inattentiveness subscales. Adverse events (AEs), vital signs, electrocardiograms (ECGs), and laboratory data were collected. The trial was conducted from January 2005 to June 2005. Results: Triple-bead MAS resulted in significantly greater improvement versus placebo in mean ADHD-RS-IV total score change (p < .0001), CGI-Improvement (p < .0001), TASS total score at 13-16 hours postdose (p = .002), BADDS total score (p < .0001), all AIM-A domains (p <= .01), and ADHD-RS-IV subscales (p < .01), demonstrating extended duration of efficacy and improvements in executive function and QOL. The most common treatment-emergent AEs included insomnia, dry mouth, decreased appetite and weight, and headache. Most treatment-emergent AEs were mild or moderate in severity. Conclusions: Triple-bead MAS was significantly more effective than placebo in treating adult ADHD. The extended duration of action up to 16 hours and significant improvements in executive function and QOL address unique treatment needs of adults with ADHD. Treatment-emergent AEs with triple-bead MAS were consistent with amphetamine treatment. Trial Registration: clinicaltrials.gov Identifier: NCT00150579 (J Clin Psychiatry 2008;69:1437-1448. Online Ahead of Print September 9, 2008.) Received May 8, 2007; accepted June 25, 2008. From the Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston (Dr. Spencer); Department of Psychiatry, New York University School of Medicine, New York (Dr. Adler); Department of Psychiatry, Duke University Medical Center, Raleigh, N.C. and Department of Psychiatry, University of North Carolina-Chapel Hill (Dr. Weisler); and Shire Development Inc., Wayne, Pa. (Dr. Youcha). Supported by funding from Shire Development Inc. These data were presented at the 160th annual meeting of the American Psychiatric Association, May 23, 2007, San Diego, Calif. Acknowledgments are listed at the end of this article. Financial disclosure is listed at the end of this article. Corresponding author and reprints: Thomas J. Spencer, M.D., Massachusetts General Hospital, Pediatric Psychopharmacology Research Unit, 55 Fruit St., Warren 705, Boston, MA 02114 (e-mail: spencer@helix.mgh.harvard.edu). |