Safety and Efficacy of ABT-089 in Pediatric Attention-Deficit/Hyperactivity Disorder: Results from Two Randomized Placebo-Controlled Clinical Trials - 10/08/11
, Laura M. Gault, M.D., Ph.D. b, Ann Childress, M.D. d, Christopher J. Kratochvil, M.D. e, Lindsey Bensman, B.S. b, Coleen M. Hall, M.S. b, Evelyn Olson, B.S. b, Weining Z. Robieson, Ph.D. b, Tushar S. Garimella, Ph.D. b, Walid M. Abi-Saab, M.D. c, George Apostol, M.D. c, Mario D. Saltarelli, M.D., Ph.D. b
Correspondence to: Dr. Timothy E. Wilens, Massachusetts General Hospital, Pediatric Psychopharmacology Unit, 55 Fruit Street, YAW 6A, Boston, MA 02114Résumé |
Objective |
To assess the safety and efficacy of ABT-089, a novel ⍺4β2 neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD).
Method |
Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years of age were conducted. Study 1 (n = 274) assessed six treatment groups over 8 weeks: 4 once-daily (QD) ABT-089 doses (0.085−0.700 mg/kg), QD atomoxetine, and placebo. Study 2 (n = 119) assessed three treatment groups over 6 weeks: 2 QD ABT-089 doses (0.7 mg/kg, 1.4 mg/kg) and placebo. The primary efficacy variable was the investigator-administered Attention-Deficit/Hyperactivity Disorder Rating Scale–IV: Home Version (ADHD-RS-IV [HV]) Total Score. Safety was assessed by adverse event (AE) monitoring, laboratory tests, vital signs, physical examinations, and electrocardiogram measures.
Results |
There was no statistically significant difference between ABT-089 and placebo in mean change from baseline to final evaluation of ADHD-RS-IV (HV) Total Score or other outcome measures at any dose in either study. In Study 1, atomoxetine showed statistically significant improvement for the primary and most secondary endpoints. ABT-089 was generally safe and well tolerated, with no statistically significant difference between any ABT-089 dose and placebo in the overall incidence of any specific AE, and no clinically significant changes in other safety measures.
Conclusions |
ABT-089 did not show efficacy on the primary efficacy variable, the ADHD-RS-IV (HV) Total Score, or other measures of ADHD symptomatology in children with ADHD, and had a safety profile similar to placebo. These results contrast with published reports of efficacy of nicotinic modulators in adults with ADHD.
Clinical Trial Registry Information- M06-888 (Study 1): A Safety and Efficacy Study of ABT-089 in Children With Attention-Deficit/Hyperactivity Disorder (ADHD), URL: www.clinicaltrials.gov, unique identifier: NCT00528697. M10-345 (Study 2): Safety and Tolerability Study of ABT-089 in Children With Attention-Deficit/Hyperactivity Disorder (ADHD), URL: www.clinicaltrials.gov, unique identifier: NCT00640419.
Le texte complet de cet article est disponible en PDF.Key Words : ADHD, pharmacologic treatment, ⍺4β2, neuronal nicotinic receptor
Plan
| Supplemental material cited in this article is available online. |
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| These studies are funded by Abbott. |
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| The authors thank the study subjects and their parents for participating in these studies, and the following contributors: Study 1 (M06-888): Edward A. Cherlin, M.D., of Valley Clinical Research, Inc.; Andrea Corsino, R.N., M.S.N., of Consultants in Neurology, Ltd.; Judith C. Fallon, M.D., of NeuroScience, Inc.; James Grimm, M.D., of the Oregon Center for Clinical Investigators; David G. Krefetz, D.O., M.D., of CRI Worldwide; Alan J. Levine, M.D., of Alpine Clinical Research Center; Leslie vH. Taylor, M.D., of the Dean Foundation for Health Research and Education; Daniel Wynn, M.D., of Consultants in Neurology, Ltd.; Study 2 (M10-345): Michael S. Greenbaum, M.D., of Capstone Clinical Research; R. Bart Sangal, M.D., of the Attention Disorders Institute; Louise Thurman, M.D., M.P.H., of the IPS Research Company; both studies: Valerie Arnold, M.D., of the University of Tennessee Center for Health Science; Beal Essink, M.D., of the Oregon Center for Clinical Investigators; Linda S. Harper, M.D., and J. Mark Joyce of Clinical Neuroscience Solutions, Inc.; and Bradley D. Vince, D.O., of Vince and Associates Clinical Research. Statistical experts were Weining Z. Robieson, Ph.D. (M06-888) and Coleen M. Hall, M.S. (M10-345), of Abbott. Medical writing support was provided in the development of this manuscript by Regula E. Egli, Ph.D., of Abbott. |
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| Disclosures: Dr. Wilens receives research support from Abbott, McNeil, Eli Lilly and Co., the National Institutes of Health - National Institute on Drug Abuse, Merck, and Shire. He has served on the speakers' bureau for Eli Lilly and Co., McNeil, Novartis, and Shire. He has served as a consultant for Abbott, AstraZeneca, McNeil, Eli Lilly and Co., the National Institutes of Health, National Institute on Drug Abuse, Novartis, Merck, and Shire. He receives royalties from Guilford Press. Dr. Childress has served as a consultant for and on the advisory boards for Novartis and Shire. She receives research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Co., Johnson and Johnson, McNeil Pediatrics, Division of Ortho-McNeil-Janssen Pharmaceuticals, Next Wave Pharmaceuticals, Novartis, Sepracor, and Shire. She serves on the speakers' bureau for Bristol-Myers Squibb, Novartis, and Shire. Dr. Kratochvil receives research support from the National Institute of Mental Health, Eli Lilly and Co., Abbott, and Somerset. He serves as a consultant for Eli Lilly and Co., Abbott, Neuroscience Education Institute, MedAvante, AstraZeneca, and Pfizer. He is the Editor of the Brown University Child and Adolescent Psychopharmacology Update, and member of the REACH Institute Primary Pediatric Psychopharmacology Steering Committee. He receives study drug for an National Institute of Mental Health-funded study from Eli Lilly and Co., and Abbott Laboratories. Drs. Gault, Robieson, Garimella, and Saltarelli, and Ms. Bensman, Ms. Hall, and Ms. Olson are employees of Abbott, and hold Abbott stock options and/or stock. Dr. Saltarelli is an Abbott patent holder. Drs. Abi-Saab and Apostol were employees of Abbott when the studies were performed, and hold Abbott stock. Dr. Abi-Saab is an Abbott patent holder. |
Vol 50 - N° 1
P. 73 - janvier 2011 Retour au numéro
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