Addressing Involuntary Movements in Tardive Dyskinesia (AIM-TD): Efficacy, Safety, and Tolerability of Fixed-Dose Deutetrabenazine for the Treatment of Moderate to Severe Tardive Dyskinesia (TD) (S56.007)

Objective: To evaluate the efficacy, safety, and tolerability of deutetrabenazine in patients with TD. Background: AIM-TD is the second large 12-week, Phase III, randomized, double-blind, placebo-controlled, parallel-group study of deutetrabenazine in moderate–severe TD. In the previous Phase II/III, randomized, placebo-controlled trial, ARM-TD, deutetrabenazine significantly improved TD compared with placebo on the Abnormal Involuntary Movement Scale (AIMS) (−3.0 vs −1.6, P =0.019) and was generally well tolerated. Design/Methods: Patients with moderate–severe TD (items 1–7) were randomized 1:1:1:1 to receive one of three fixed-dose regimens of deutetrabenazine (12 mg/day, 24 mg/day, 36 mg/day) or placebo. The primary efficacy endpoint was change in AIMS from baseline to Week 12 for patients with a blinded central video AIMS rating ≥6 at baseline. The key secondary endpoint was treatment success (proportion of patients who were “much improved” or “very much improved”) on the Clinical Global Impression of Change (CGIC) at Week 12. Adverse events (AEs), clinical labs, and 12-lead ECGs were monitored. Results: The mean AIMS score from baseline to Week 12 improved by −3.3 points for deutetrabenazine 36 mg/day (treatment difference −1.9, P =0.001), −3.2 points for 24 mg/day (−1.8, P =0.003), and −2.1 points for 12 mg/day (−0.7, P =0.217) compared with −1.4 points in placebo. On the CGIC, treatment success was achieved in 44% of patients taking 36 mg/day ( P =0.059) and 49% taking 24 mg/day ( P =0.014) versus 26% taking placebo. The AE incidence in deutetrabenazine-treated patients (47.1%) was similar to the placebo group (47.2%); most AEs were mild or moderate. Discontinuations for AEs and serious AEs occurred at similar rates between groups. Conclusions: Deutetrabenazine at 24 mg/day and 36 mg/day provided clinically significant benefits, including reduction in abnormal involuntary movements on AIMS. Improvements were appreciated by clinicians, shown by improvements on the CGIC. Fixed-dose deutetrabenazine was generally well tolerated. 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. 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. 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. 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.