Deutetrabenazine Treatment Response by Concomitant Dopamine-Receptor Antagonists in the Phase III, Randomized, Double-Blind, Placebo-Controlled AIM-TD Trial in Tardive Dyskinesia (TD) (P2.016)

Objective: To determine the impact of dopamine-receptor antagonist (DRA) use at baseline on the efficacy, safety, and tolerability of deutetrabenazine in patients with TD. Background: TD results from DRA exposure. Continued administration of DRAs may mask and eventually worsen symptoms. Treating TD without disrupting treatment for any underlying psychiatric condition is optimal. Clinically significant reductions in involuntary movements with deutetrabenazine treatment were seen the AIM-TD study. Design/Methods: In AIM-TD, patients meeting study criteria were randomized (1:1:1:1) to receive fixed-dose deutetrabenazine (12 mg/day, 24 mg/day, 36 mg/day) or placebo. Randomization was stratified on baseline DRA use (currently taking or not). The primary endpoint of mean change in Abnormal Involuntary Movement Scale (AIMS) score from baseline to Week 12 was analyzed, taking into consideration patients’ use of DRAs at baseline. Results: Mean change in AIMS score at Week 12 in patients taking DRA at baseline was −3.4 points for 36 mg/day (n=35; treatment difference −1.7, P =0.017), −3.3 points for 24 mg/day (n=37; −1.5, P =0.036), and −2.1 points for 12 mg/day (n=45; −0.2, P =0.745), compared with −1.7 points in placebo (n=45). Mean change in AIMS at Week 12 in patients not taking DRAs at baseline was −3.3 points for 36 mg/day (n=20; −3.0, P =0.006), −3.2 points for 24 mg/day (n=12; −3.0, P =0.013), and −2.8 points for 12 mg/day (n=15; −2.4, P =0.048), compared with −0.1 points in placebo (n=13). The overall incidence of adverse events was similar to placebo in all groups, regardless of baseline DRA use. Conclusions: Regardless of DRA use, fixed-dose regimens of deutetrabenazine provided clinically significant reductions in abnormal involuntary movements of TD, and showed a favorable safety/tolerability profile. Greater reductions were observed in patients not taking DRAs, possibly due to masking of TD symptoms by DRAs. Study Supported by: This study was funded by Teva Branded Pharmaceutical Products Ru0026D, Inc. Petach Tikva, Israel Disclosure: 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. 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. Dr. Stamler has received personal compensation for activities with Auspex Pharma as an employee. Dr. Davis has received personal compensation for activities with Teva Pharmaceuticals as an employee. 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. 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. Ondo has received personal compensation for activities with TEVA, UCB Pharma, Lundbeck Research USA, Inc, ACADIA, and IMPAX as speaker and consultant. 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