Confirmed Safety of Deutetrabenazine for Tardive Dyskinesia in a 2-Year Open-Label Extension Study (P4.075)

Objective: To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2 years. Background: In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. Design/Methods: Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week 106). Results: 343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon. Conclusions: These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients. Study Supported by: This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel. Disclosure: Dr. Fernandez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Prime Education, Inc., International Parkinson and Movement Disorders Society, Carling Communications, Medscape (speaker in CME events), AbbVie, Biogen, GE Health Care, Inventiv, Kyowa Hakko Kirin, Lundbeck, Merz Pharmaceuticals, Voyager, Sunovion, Pfizer. Dr. Fernandez has received personal compensation in an editorial capacity for International Parkinson and Movement Disorders Society for serving as Medical Editor of the MDS Web Site. Dr. Fernandez has received research support from AbbVie, Acadia, Teva, Biotie/Acorda Therapeutics, Civitas, Kyowa/Prostrakan, Michael J. Fox Foundation, Movement Disorders Society, NIH/NINDS, Parkinson Study Group, Rhythm, Synosia. Dr. Stamler has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Auspex Pharmaceuticals. Dr. Davis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva Pharmaceutical Industries. Dr Factor has nothing to disclose. Dr. Hauser has nothing to disclose. Dr. Jimenez-Shahed has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva, St. Jude Medical, Medtronic. Dr. Jimenez-Shahed has received research support from Avid Radiopharmaceuticals, Acadia Pharmaceuticals, St. Jude Medical, Biotie, Michael J. Fox Foundation. Dr. Ondo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva, Lundbeck, UCB, US WorldMeds, Acadia. Dr. Ondo has received research support from dbeck, Tremor Research Group, Dystonia Coalition, Restless Leg Syndrome Foundation, Acorda. Dr. Jarskog has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Jarskog has received research support from Auspex/Teva, Boehringer Ingelheim, Otsuka, NIH. Dr. Woods has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Boehringer Ingelheim, Nutria Health. Dr. Woods has received research support from Teva, Pfizer. Dr. LeDoux has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck, Acadia. Consulting: Teva Neuroscience, US WorldMeds, the Mayo Clinic, Starnes-Davis-Florie, Michael J. Fox Foundation, Benign Essential Blepharospasm Research Foundation, Dorothy/Daniel Gerwin Parkinson’s Research Fund, Auspex, Teva, Acorda, CHD. Dr. LeDoux has received personal compensation in an editorial capacity for Elsevier (for editing ‘Animal Models of Movement Disorders’ and ‘Movement Disorders: Genetics and Models’). Dr. Shprecher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva, Lundbeck. Dr. Shprecher has received research support from Arizona Alzheimer’s Consortium, Adamas, Teva, Kyowa, MJFF, Neurocrine, NIH. Dr. Anderson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with North American study Co-Principal Investigator for LEGATO-HD, Global Principal Investigator for AIM-TD, and Global Co-Principal Investigator for ARM-TD. Site Principal Investigator for Pride-HD, First-HD, ARC-HD: Teva. Scientific Advisor, Site Principal I.