Study concept and design: Cummings, Lyketsos, Peskind, Scharre, Davis, Shin, Tariot, Siffert.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Cummings, Porsteinsson, Nguyen, Siffert.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Davis, Shin, Siffert.
Obtained funding: Siffert.
Administrative, technical, or material support: Nguyen, Shin, Tariot, Siffert.
Study supervision: Cummings, Scharre, Shin, Tariot, Siffert.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Cummings has received in-kind research support from Avid Radiopharmaceuticals and Teva Pharmaceuticals. He has provided consultation to AbbVie, Acadia, ADAMAS, Alzheon, Anavex, AstraZeneca, Avanir, Biogen-Idec, Biotie, Boehringer-Ingelheim, Chase, Eisai, Forum, Genentech, Grifols, Intracellular Therapies, Lilly, Lundbeck, Merck, Neurotrope, Novartis, Nutricia, Otsuka, Pfizer, Prana, QR Pharma, Resverlogix, Roche, Sonexa, Suven, Takeda, and Toyoma companies. He has provided consultation to GE Healthcare and MedAvante and owns stock in ADAMAS, Prana, Sonexa, MedAvante, Neurotrax, and Neurokos. Dr Cummings owns the copyright of the Neuropsychiatric Inventory. Dr Lyketsos reports receiving grant support (research or continuing medical education) from National Institute of Mental Health (NIMH), National Institute on Aging (NIA), Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, GlaxoSmithKline, Eisai, Pfizer, AstraZeneca, Lilly, Ortho-McNeil, Bristol-Myers Squibb, Novartis, National Football League, Elan, and Functional Neuromodulation. He has received payment as consultant or advisor for AstraZeneca, GlaxoSmithKline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Eli Lilly, Pfizer, Genentech, Elan, NFL Players Association, NFL Benefits Office, Avanir, Zinfandel, Bristol-Myers Squibb, AbbVie, Janssen, Orion, Otsuka, Servier, and Astellas and honoraria or travel support from Pfizer, Forest, GlaxoSmithKline, and Health Monitor. Dr Peskind receives research grant support from the Department of Veterans Affairs, NIA, Eli Lilly, and Accera and has received payment as a consultant to Avanir, Eli Lilly, and Takeda. Dr Porsteinsson reports receiving grants to his institution from AstraZeneca, Avanir, Baxter, Biogen, Bristol-Myers Squibb, Eisai, Elan, EnVivo, Genentech/Roche, Janssen Alzheimer Initiative, Medivation, Merck, Pfizer, Toyama, Transition Therapeutics, the National Institutes of Health (NIH), NIMH, NIA, and Department of Defense and being a paid consultant for Elan, Janssen Alzheimer Initiative, Lundbeck, Pfizer, and TransTech Pharma. He holds a membership on data and safety monitoring boards for Quintiles, Functional Neuromodulation, and the New York State Psychiatric Institute and has participated on a speaker’s bureau for Forest and developed educational presentations for CME Inc and PeerView Institute. Dr Mintzer receives grant support from Takeda, Avanir, Genentech, NIA/NIH, Alzheimer’s Disease Neuroimaging Initiative, Elan, Eli Lilly, Grifols, Pfizer, and Roche and is majority owner of BioPharma Connex; BioPharma Connex was involved in facilitating nursing home recruitment for this study. He is also vice president of medical affairs for NeuroQuest. Dr Scharre has received consulting fees from Eli Lilly, Brain Test, Lundbeck, Avanir, and the Alois Alzheimer Foundation and has received grants to his institution for research from Lundbeck, Merck, Eli Lilly, Forum, Brain Test, AstraZeneca, Phylogeny, and Avanir. Dr De La Gandara has received support for clinical trials from Avanir Pharmaceuticals Inc, Elan, Transition Therapeutics, Janssen, Pfizer, Eli Lilly, Avid Pharmaceuticals, Novartis, Eisai, Chase, Gliacure Inc, Bristol-Myers Squibb, Grifols, Merck, GlaxoSmith Kline, Myriad, and Forest. Dr Tariot has received consulting fees from AbbVie, AC Immune, Boehringer-Ingelheim, Chase Pharmaceuticals, CME Inc, Medavante, Otsuka, and Sanofi-Aventis. He has received consulting fees and research support from AstraZeneca, Avanir, Bristol-Myers Squibb, Cognoptix, Janssen, Merck, Roche, and Takeda and research support only from Baxter Healthcare Corp, Functional Neuromodulation, GE, Genentech, Novartis, Pfizer, and Targacept. Dr Tariot has received other research support from the NIA and Arizona Department of Health Services and holds stock options in ADAMAS. Dr Davis has been a paid consultant for Avanir Pharmaceuticals Inc since 2011 and advised in the design, statistical analysis plan, and interpretation of these study data. Dr Davis also consults for Avanir across all other development programs including programs in depression, pain, migraine, and Parkinson disease. Dr Davis is president of CSD Biostatistics Inc, a statistical consulting company providing services to numerous pharmaceutical and other health care companies. Ms Nguyen, Mr Shin, and Dr Siffert are employees of Avanir and may hold stock or options. No other disclosures are reported.
Funding/Support: This study was funded by Avanir Pharmaceuticals Inc.
Role of the Funder/Sponsor: Avanir Pharmaceuticals had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The sponsor had no veto rights regarding the decision to submit the manuscript for publication.
Previous Presentation: The data from this study have been partially presented at the 139th Annual Meeting of the American Neurological Association; Baltimore, Maryland; October 13, 2014; and at the 2015 annual Alzheimer’s Association International Conference; Washington, DC; July 22, 2015.
Additional Contributions: We acknowledge Maurizio Fava, MD, Massachusetts General Hospital (protocol design); Shereen McIntyre, MBA, Avanir (clinical data management and data analysis); Nadine Knowles, BA, Avanir (project management, protocol development, study startup training); Andrea E. Formella, PharmD, BCPP, Avanir (editorial assistance); Shelby L. Woods, Avanir (publication project management); Catherine Trinh Nguyen, BS, BA, Avanir; Jessie C. Nguyen, BS, Avanir (clinical research associate); Viola de Jong, RPH, CCRA, Avanir, Julia Degenhard, NP, Cognitive Research Corp, and Deborah Lees, BSN, Cognitive Research Corp (clinical monitoring of study sites and data monitoring); Gary G. Kay, PhD, Cognitive Research Corp (training of clinical raters); Ammie Z. Hill, MD, MMS Holdings Inc (medical monitor); Harry Haber, MPH, MMS Holdings Inc, and Linda LaMoreaux, MPH, MMS Holdings Inc (statistical analysis). Medical writing assistance was provided by John H. Simmons, MD, Peloton Advantage LLC, and was supported by Avanir. These persons received no compensation apart from usual salary for their contributions. We are grateful to all of the patients, caregivers, and families who volunteered for this study and to the investigators and their teams who made the study conduct possible.