46 Confirmed Safety of Deutetrabenazine for Tardive Dyskinesia in a 2-Year Open-label Extension Study

Hubert H. Fernandez, David Stamler, Mat D. Davis, Stewart A. Factor, Robert A. Hauser, Joohi Jimenez-Shahed, William G. Ondo, L. Fredrik Jarskog, Scott W. Woods, Mark Ledoux, David R. Shprecher, Karen E. Anderson

Research output: Contribution to journalArticle

Abstract

Study ObjectiveTo evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years. 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. METHOD: 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 12mg/day, titrating up to a maximum total daily dose of 48mg/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 (Week106). 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.Presented at: American Academy of Neurology Annual Meeting; April 21-27, 2018, Los Angeles, California,USAFunding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

Original languageEnglish (US)
Number of pages1
JournalCNS spectrums
Volume24
Issue number1
DOIs
StatePublished - Feb 1 2019

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Safety
Placebos
Psychomotor Agitation
Incidence
Suspensions
deutetrabenazine
Tardive Dyskinesia
Los Angeles
Dyskinesias
Parkinsonian Disorders
Israel
Diarrhea
Therapeutics
Anxiety
Depression
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Fernandez, H. H., Stamler, D., Davis, M. D., Factor, S. A., Hauser, R. A., Jimenez-Shahed, J., ... Anderson, K. E. (2019). 46 Confirmed Safety of Deutetrabenazine for Tardive Dyskinesia in a 2-Year Open-label Extension Study. CNS spectrums, 24(1). https://doi.org/10.1017/S1092852919000397

46 Confirmed Safety of Deutetrabenazine for Tardive Dyskinesia in a 2-Year Open-label Extension Study. / Fernandez, Hubert H.; Stamler, David; Davis, Mat D.; Factor, Stewart A.; Hauser, Robert A.; Jimenez-Shahed, Joohi; Ondo, William G.; Jarskog, L. Fredrik; Woods, Scott W.; Ledoux, Mark; Shprecher, David R.; Anderson, Karen E.

In: CNS spectrums, Vol. 24, No. 1, 01.02.2019.

Research output: Contribution to journalArticle

Fernandez, HH, Stamler, D, Davis, MD, Factor, SA, Hauser, RA, Jimenez-Shahed, J, Ondo, WG, Jarskog, LF, Woods, SW, Ledoux, M, Shprecher, DR & Anderson, KE 2019, '46 Confirmed Safety of Deutetrabenazine for Tardive Dyskinesia in a 2-Year Open-label Extension Study', CNS spectrums, vol. 24, no. 1. https://doi.org/10.1017/S1092852919000397
Fernandez, Hubert H. ; Stamler, David ; Davis, Mat D. ; Factor, Stewart A. ; Hauser, Robert A. ; Jimenez-Shahed, Joohi ; Ondo, William G. ; Jarskog, L. Fredrik ; Woods, Scott W. ; Ledoux, Mark ; Shprecher, David R. ; Anderson, Karen E. / 46 Confirmed Safety of Deutetrabenazine for Tardive Dyskinesia in a 2-Year Open-label Extension Study. In: CNS spectrums. 2019 ; Vol. 24, No. 1.
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abstract = "Study ObjectiveTo evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years. 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. METHOD: 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 12mg/day, titrating up to a maximum total daily dose of 48mg/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 (Week106). 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.Presented at: American Academy of Neurology Annual Meeting; April 21-27, 2018, Los Angeles, California,USAFunding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.",
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T1 - 46 Confirmed Safety of Deutetrabenazine for Tardive Dyskinesia in a 2-Year Open-label Extension Study

AU - Fernandez, Hubert H.

AU - Stamler, David

AU - Davis, Mat D.

AU - Factor, Stewart A.

AU - Hauser, Robert A.

AU - Jimenez-Shahed, Joohi

AU - Ondo, William G.

AU - Jarskog, L. Fredrik

AU - Woods, Scott W.

AU - Ledoux, Mark

AU - Shprecher, David R.

AU - Anderson, Karen E.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Study ObjectiveTo evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years. 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. METHOD: 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 12mg/day, titrating up to a maximum total daily dose of 48mg/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 (Week106). 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.Presented at: American Academy of Neurology Annual Meeting; April 21-27, 2018, Los Angeles, California,USAFunding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

AB - Study ObjectiveTo evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years. 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. METHOD: 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 12mg/day, titrating up to a maximum total daily dose of 48mg/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 (Week106). 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.Presented at: American Academy of Neurology Annual Meeting; April 21-27, 2018, Los Angeles, California,USAFunding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

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