Accepted for Publication: June 8, 2012.
Published Online: August 13, 2012. doi:10.1001/archneurol.2012.2194
Author Contributions:Study concept and design: Coric, Salloway, Brody, Colby, Albright, Feldman, and Berman. Acquisition of data: Coric, van Dyck, Salloway, Andreasen, Brody, Richter, Soininen, Shiovitz, Pachai, Portelius, Andreasson, Blennow, Soares, Feldman, and Berman. Analysis and interpretation of data: Coric, van Dyck, Salloway, Thein, Shiovitz, Pilcher, Rollin, Dockens, Pachai, Portelius, Blennow, Soares, Feldman, and Berman. Drafting of the manuscript: Coric, Andreasen, Thein, Rollin, Pachai, Andreasson, Soares, Feldman, and Berman. Critical revision of the manuscript for important intellectual content: Coric, van Dyck, Salloway, Brody, Richter, Soininen, Thein, Shiovitz, Pilcher, Colby, Rollin, Dockens, Pachai, Portelius, Blennow, Soares, Albright, Feldman, and Berman. Statistical analysis: Rollin and Pachai. Administrative, technical, and material support: Coric, van Dyck, Andreasen, Brody, Richter, Thein, Colby, Andreasson, Blennow, Feldman, and Berman. Study supervision: Coric, van Dyck, Soininen, Albright, Feldman, and Berman.
Conflict of Interest Disclosures: Dr van Dyck reported serving as a consultant to Bristol-Myers Squibb, Janssen Alzheimer Immunotherapy, Pfizer Inc, GlaxoSmithKline, and Elan Pharmaceuticals. He reported receiving research support from Bristol-Myers Squibb, Elan Pharmaceuticals, Janssen Alzheimer Immunotherapy, Pfizer Inc, Eli Lilly, Baxter Pharmaceuticals, GlaxoSmithKline, Medivation, Inc, and the National Institute of Aging and Alzheimer's Association. Dr Salloway reported serving as a consultant to Elan Pharmaceuticals, Janssen Alzheimer Immunotherapy, Astra-Zeneca, Avid-Lilly, Baxter, Pfizer Inc, Eisai, Athena, and Bristol-Myers Squibb. He reported receiving honoraria from Eisai, Pfizer Inc, Elan Pharmaceuticals, Bristol-Myers Squibb, and Athena Diagnostics. He reported receiving research support from Elan Pharmaceuticals, Janssen Alzheimer Immunotherapy, Bristol-Myers Squibb, Eisai, Pfizer Inc, Medivation, Inc, Genentech, Bayer, GE, NIA Alzheimer's Disease Neuroimaging Initiative, NIA Dominantly Inherited Alzheimer's Network, the Alzheimer's Association, The Norman and Rosalie Fain Family Foundation, the John and Happy White Foundation, and the Champlin Foundation. Dr Brody's institution reported receiving grant and travel support from Bristol-Myers Squibb. Dr Soininen reported receiving grant support from Bristol-Myers Squibb and the Academy of Finland and serving as a consultant to ACImmune. Dr Thein reported receiving grant support from Abbot, Astellas, Biogen Idec, Chiesi, Elan Pharmaceuticals, Genentech, Janssen Alzheimer Immunotherapy, Merck, Eli Lilly, Medivation, Inc, Pfizer Inc, and Toyama. He reported serving as a consultant to Eli Lilly, Guidepoint, Gerson Lehman Group, and Clinical Advisors LLC, and reported receiving travel support to investigator meetings from Bristol-Myers Squibb. Dr Shiovitz reported receiving research support from Abbott, Astellas, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Chiesi, Elan Pharmaceuticals, Forest, Eli Lilly, Eisai, Epix, GlaxoSmithKline, Janssen Alzheimer Immunotherapy, Johnson & Johnson, Lundbeck, Novartis, Merck, Organon, Otsuka, Pfizer Inc, Praecis, sanofi-aventis, Shire, Solvay, Sunovion, Takeda, and Targacept. Dr Portelius reported receiving travel support from Bristol-Myers Squibb. Dr Blennow reported receiving grant support from Bristol-Myers Squibb, serving as a speaker for Janssen Alzheimer Immunotherapy, and sitting on Advisory Boards for Pfizer Inc, Immunogenetics, and Probiodrug.
Funding/Support: This study was supported by Bristol-Myers Squibb.
Additional Contributions: Our deepest appreciation to the patients who participated in this clinical trial. We are grateful for the hard work and efforts of the following principal investigators and their clinical staff: Niels Andreasen, Jeffrey Apter, Vinod Bhatnagar, John Brockington, Mark Brody, Anna Burke, Craig Curtis, Vithalbhai Dhaduk, Martin Farlow, Mildred Farmer, Stephen Flitman, Gary Gerard, Joshua Grill, Lawrence Honig, Saleem Ismail, Marvin Kalafer, Bruce Kohrman, David Margolin, Lennart Minthon, Mahmoud Okasha, Omid Omidvar, Joseph Pittard, Ralph Richter, Juha Rinne, Joel Ross, Marwan Sabbagh, Stephen Salloway, Douglas Scharre, Thomas Shiovitz, Amanda Smith, Hilkka Soininen, John Stoukides, Leslie Taylor, Stephen Thein, Christopher van Dyck, Anders Wallin, Myron Weiner, Richard Weisler, Kerri Louise Wilks, Lene Wermuth, and Tanya Vapnik. We also thank the γ-Secretase Inhibitor Development Team for their outstanding implementation of this study protocol, including Caroline Clairmont, PhD, James Hazel, BSN, RN, Stephen Kaplita, MS, Olive Watson-Coleman, RN, MPH, Tamara Bratt, MHS, Leah Burns, MPH, Randy Slemmon, PhD, Nina Cerruti, BS, Jian Han, PhD, Sandeep Kumar, MD, Sue Behling, BS, MT, ASCP, Christina Smith, PhD, Kathleen Szymczak, BS, Yong Lu, MS, Maria Klockare, BSc, Katherine Ciarlone, Jenny Bjorkvall, BA, Laura Ruggiero, BS, Deborah Howe, BS, Beth Morris, BA, and Patricia Ambrose, MBA. We are grateful to Jun-Sheng Wang, PhD, Malaz AbuTarif, PhD, and Brian McHugh, PhD, for their pharmacokinetic modeling, simulation, and analyses in supporting our dosing strategy. We thank the biomarkers group for their support including Paul Rhyne, PhD, Flora Berisha, MS, and Holly Soares, PhD. We also thank Thomas Blaetter, MD, for his contributions to the study protocol while employed at BMS. Finally, we are appreciative for the scientific guidance and insight provided by Elliot Sigal, MD, PhD, Brian Daniels, MD, Doug Manion, MD, and Jane Tiller, MD. We also acknowledge the editorial and technical support of Brian Atkinson, PhD, Bristol-Myers Squibb.