Addressing Involuntary Movements in Tardive Dyskinesia (AIM-TD): Effect of Fixed-Dose Deutetrabenazine by Baseline Comorbidities

Objective: To assess the efficacy and safety of deutetrabenazine in patients with TD as a function of underlying disease. Background: TD, an involuntary movement disorder, results from exposure to dopamine-receptor antagonists that are typically prescribed for psychiatric illnesses. In AIM-TD, clinically significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores were seen with deutetrabenazine 24 mg/day and 36 mg/day treatment at Week 12 compared with placebo. Design/Methods: AIM-TD is a 12-week, Phase III, randomized, double-blind, placebo-controlled study that evaluated the efficacy, safety, and tolerability of fixed-dose regimens (12 mg/day, 24 mg/day, and 36 mg/day) of deutetrabenazine for the treatment of moderate–severe TD. Change in AIMS scores from baseline to Week 12, treatment success (“much improved” or “very much improved”) at Week 12 based on the Clinical Global Impression of Change (CGIC), and adverse events (AEs) were analyzed based on baseline psychiatric illness type (schizophrenia/schizoaffective disorder or bipolar disorder/depression/other). Results: At Week 12, deutetrabenazine 24 mg/day and 36 mg/day demonstrated clinically meaningful improvements from baseline in AIMS scores for patients with baseline bipolar disorder/depression/other (least-squares [LS] mean: −3.1 [SE: 0.73] and −3.6 [0.61], respectively; placebo: −0.5 [0.63]), and patients with schizophrenia/schizoaffective disorder (LS mean: −3.2 [0.59]; −3.0 [0.59], respectively; placebo: −1.9 [0.56]) compared with placebo. Deutetrabenazine 24 mg/day and 36 mg/day had higher odds of treatment success on CGIC in patients with bipolar disorder/depression/other (odds ratio [OR]: 2.69; P =0.110 and 5.26; P =0.010, respectively) compared with placebo. Deutetrabenazine 24 mg/day had higher odds of treatment success on CGIC in patients with baseline schizophrenia/schizoaffective disorder (OR: 2.57; P =0.073), while 36 mg/day did not (OR: 0.88; P =0.833); AE rates, including neuropsychiatric AEs, were similar in all groups, regardless of underlying disease type. Conclusions: Deutetrabenazine provided clinically meaningful improvements in AIMS scores and CGIC regardless of psychiatric illness type, with a favorable safety/tolerability profile. Study Supported by: This study was funded by Teva Branded Pharmaceutical Products Ru0026D, Inc. Petach Tikva, Israel Disclosure: Dr. Anderson has received personal compensation for activities with LEGATO-HD, AIM-TD, ARM-TD studies. Pride-HD, First-HD, ARC-HD, and Teva CNSu003e Dr. Factor has received personal compensation for activities with Lundbeck, TEVA, Neurocrine, Avanir, Cynapsus, and Adamas as a consultant and from Uptodate as a speaker. Dr. Factor has received research support from Ipsen, Auspex/Teva, US World Meds, Pharm-Olam, Cynapsus Therapeutics, Solstice, CHDI Foundation, Michael J. Fox Foundation, NIH and Medtronic. Dr. Davis has received personal compensation for activities with Teva Pharmaceuticals as an employee. Dr. Hauser has received personal compensation for activities with Guidepoint Global, SAI-Mmed Partners, Scienomics Group, Gerson Lehrman Group, LCN Consulting, Putnam Associates, National Parkinson Foundation, eResearch Technology, Inc., Lundbeck LLC, Krog u0026 Partners, and Cynapsus as a consultant. Dr. Hauser has received licensing fee payments from the University of South Florida. Dr. Hauser has received research support from Abbvie Pharmaceutical Research and Development, Acadia Pharmaceuticals, Astra Zeneca, Biotie Therapies, Acorda Therapeutics, Inc., Civitas, Impax Pharmaceuticals, and Kyowa Kirin Pharma. Dr. Isojarvi has received personal compensation for activities with Lundbeck LLC as an employee. Dr. Jimenez -hahed has received personal compensation for activities with Teva, St. Jude Medical and Medtronic as a consultant. Dr. Jimenez Shahed has received research support from Avid Radiopharmaceuticals, Acadia Pharmaceuticals and St. Jude Medical. Dr. Stamler has received personal compensation for activities with Auspex Pharma as an employee. Dr. Ondo has received personal compensation for activities with TEVA, UCB Pharma, Lundbeck Research USA, Inc, ACADIA, and IMPAX as speaker and consultant. Dr. Fernandez has received personal compensation for activities with Prime Education Inc, Carling Communications, Medscape, Biogen, GE Health Care, Lundbeck, Merz Pharmaceuticals and Pfizer Pharmaceuticals. Dr. Fernandez has received personal compensation for activities in an editorial capacity for the MDS Web Site. Dr. Fernandez has received royalty payments from Demos Publishing. Dr. Fernandez has received research support from Abbvie, Acadia, Auspex/Teva, Biotie/Acorda Therapeutics, Civitas, Kyowa/Prostrakan, Michael J. Fox Foundation, Movement Disorders Society, NIH/NINDS, Parkinson Study Group, Rhythm, Synosia, and Teva.