6 results
Reliability of the Clinician’s Tardive Inventory (CTI)
- Richard M. Trosch, Cynthia L. Comella, Stanley N. Caroff, William G. Ondo, Alicia C. Shillington, Brandon J. LaChappelle, Robert A. Hauser, Christof U. Correll, Joseph H. Friedman
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, p. 219
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Objectives
Currently utilized clinician-rated symptom scales for tardive dyskinesia (TD) have not kept up with the expanding spectrum of TD phenomenology. The objective of this study was to develop and test the reliability of a new instrument, the CTI.
MethodsA movement disorder neurologist devised the outline of the scale. A steering committee (four neurologists and two psychiatrists) provided revisions until consensus was reached. The resulting instrument assesses frequency of abnormal movements of the eye/eyelid/face, tongue/mouth, jaw, limb/trunk, complex movements (e.g., handwringing, self-caressing), and vocalizations. The CTI rates symptoms from 0–3 with 0 = absent, 1 = infrequent/intermittent or only present with activating maneuvers, 2 = frequent intermittent, brief periods without movements, 3 = constant or nearly constant. Functional impairments including activities of daily living (ADL), social impairment, symptom bother, and harm are rated 0–3 with 0 = patient is unaware or unaffected, 1 = symptoms mildly impact patient, 2 = symptoms moderately impact patient, 3 = symptoms severely impact patient. Following institutional review board approval, the CTI underwent inter-rater and test-retest reliability testing. Videos of patient TD examinations were obtained and reviewed by two movement disorder specialists to confirm the diagnosis of TD by consensus and the adequacy to demonstrate a TD-consistent movement. Vignettes were created to include patients’ symptom descriptions and functional, social, or occupational impairments/limitations. Four clinicians rated each video/vignette. Selected videos/vignettes were also subject to an intra-rater retest. Interrater agreement was analyzed via 2-way random-effects interclass correlation (ICC) and test-retest agreement assessment utilizing Kendall’s tau-b.
Results45 video/vignettes were assessed for interrater reliability, and 16 for test-retest reliability. ICCs for movement frequency were as follows: abnormal eye movement .89; abnormal tongue/mouth movement .91; abnormal jaw movement .89; abnormal limb movement .76; complex movement .87; abnormal vocalization .77; and functional impairments including harm .82; social embarrassment .88; ADLs .83; and symptom bother .92. Retests were conducted on mean (SD) 15 (3) days later with scores ranging from .66–.87.
ConclusionsThe CTI is a new instrument with good reliability in assessing TD symptoms and functional impacts. Future validation study is warranted.
FundingNeurocrine Biosciences
45 Long-term Treatment with Deutetrabenazine Is Associated with Continued Improvement in Tardive Dyskinesia: Results from an Open-label Extension Study
- Robert A. Hauser, Hubert H. Fernandez, David Stamler, Mat D. Davis, Stewart A. Factor, Joohi Jimenez-Shahed, William G. Ondo, L. Fredrik Jarskog, Scott W. Woods, Mark S. LeDoux, David R. Shprecher, Karen E. Anderson
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, pp. 200-201
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Study Objective
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
BackgroundIn the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
MethodPatients with TD 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 and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
Results343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
ConclusionsPatients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
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 S. LeDoux, David R. Shprecher, Karen E. Anderson
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, p. 201
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Study Objective
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
BackgroundIn 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.
MethodPatients 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).
Results343 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.
ConclusionsThese 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,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
158 Long-Term Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia: Results From an Open-Label, Long-Term Study
- Karen E. Anderson, Mat D. Davis, Stewart A. Factor, Robert A. Hauser, L. Fredrik Jarskog, Joohi Jimenez-Shahed, Rajeev Kumar, Stanislaw Ochudlo, William G. Ondo, Hubert H. Fernandez
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- Journal:
- CNS Spectrums / Volume 23 / Issue 1 / February 2018
- Published online by Cambridge University Press:
- 15 June 2018, p. 97
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Introduction
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.
ObjectiveTo evaluate the long-term safety/tolerability and efficacy of deutetrabenazine in patients with TD. Week 54 open-labelresults are reported in this interim analysis.
MethodsPatients with TD 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. Safetymeasures included incidence of adverse events (AEs), serious AEs (SAEs), drug-related AEs, and AEs leading to withdrawal, dose reduction, or dose suspension. This analysis reports results up to Week 54.
Results304 patients enrolled in the extension study. There were 215 patient-years of exposure in this analysis, and exposure-adjusted incidence rates (EAIRs) of AEs (incidence/patient-years) were comparable to or lower than those observed with short-term deutetrabenazine treatment and placebo. The frequency of SAEs (EAIR 0.14) was similar to rates observed with short-termplacebo (EAIR 0.33) and deutetrabenazine (EAIR range 0.06–0.33) treatment. AEs leading to study discontinuation (EAIR 0.08), dose reduction (EAIR 0.17), and dose suspension (EAIR 0.09) were uncommon.
ConclusionsLong-term treatment with deutetrabenazine was generally safe and well tolerated in patients with TD, and did not result in cumulative toxicity.
Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.
Funding AcknowledgementsThis study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
149 Deutetrabenazine for the Treatment of Tardive Dyskinesia: Results From an Open-Label, Long-Term Study
- Karen E. Anderson, Mat D. Davis, Stewart A. Factor, Robert A. Hauser, L. Fredrik Jarskog, Joohi Jimenez-Shahed, Rajeev Kumar, FRCPC, Stanislaw Ochudlo, William G. Ondo, Hubert H. Fernandez
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- Journal:
- CNS Spectrums / Volume 23 / Issue 1 / February 2018
- Published online by Cambridge University Press:
- 15 June 2018, pp. 92-93
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Introduction
Tardive dyskinesia (TD) is an involuntary movement disorder resulting from exposure to dopamine-receptor antagonists. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.
ObjectiveTo evaluate the efficacy and safety of long-term deutetrabenazine therapy in patients with TD.
MethodsPatients with TD who completed the ARM-TD or AIM-TD studies were eligible to enter this open-label, single-arm, long-term safety study after they completed the 1-week washout period and final evaluation in the blinded portion of the trial. Efficacy endpoints included the change in AIMS score from baseline, and treatment success (defined as “much improved” or “very much improved”) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC). This analysis reports results up to Week 54.
Results304 patients enrolled in the extension study. At Week 54, the mean (standard error) change in AIMS score was –5.1 (0.52). After 6 weeks of deutetrabenazine treatment, the proportion of patients who achieved treatment success was 58% per the CGIC and 53% per the PGIC, and by Week 54 was 72% per the CGIC and 59% per the PGIC, thus demonstrating maintenance or enhancement of benefit over time. Deutetrabenazine was well tolerated for up to 54 weeks, and compared with the ARM-TD and AIM-TD studies, no new safety signals were detected.
Conclusions54 weeks of deutetrabenazine treatment was generally efficacious, safe, and well tolerated in patients with TD.
Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.
Funding AcknowledgementsThis study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
134 Improvements in Clinical Global Impression of Change With Deutetrabenazine Treatment in Tardive Dyskinesia From the ARM-TD and AIM-TD Studies
- Hubert H. Fernandez, Mat D. Davis, Stewart A. Factor, Robert A. Hauser, L. Fredrik Jarskog, Joohi Jimenez-Shahed, Rajeev Kumar, Stanislaw Ochudlo, William G. Ondo, Karen E. Anderson
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- Journal:
- CNS Spectrums / Volume 23 / Issue 1 / February 2018
- Published online by Cambridge University Press:
- 15 June 2018, p. 84
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Introduction
Tardive dyskinesia (TD) is an involuntary movement disorder that is often irreversible, can affect any body region, and can be debilitating. In the ARM-TDand AIM-TD studies, deutetrabenazine treatment demonstrated statistically and clinically significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo (primary endpoint).
ObjectiveTo evaluate the efficacy of deutetrabenazine, as measured by the Clinical Global Impression of Change (CGIC) scale, in patients with TD from the pooled ARM-TDand AIM-TD (24 and 36 mg/day doses) data sets, as compared with the pooled placebo cohort.
MethodsARM-TD and AIM-TD were 12-week, randomized, double-blind, placebo-controlled studies that evaluated the safety and efficacy of deutetrabenazine for thetreatment of TD. The key secondary endpoint of each study was the proportion of patients “much improved” or “very much improved” (treatment success) at Week 12 on theCGIC.
ResultsAt Week 12, the odds of treatment success among patients treated with deutetrabenazine (n=152) was more than double that of patients given placebo (n=107; odds ratio: 2.12; P=0.005). In a categorical analysis of CGIC ratings, patients treated with deutetrabenazine showed greater improvement than patients given placebo (P=0.003). Patients treated with deutetrabenazine also had a significantly better treatment response than those given placebo (least-squares mean CGIC score treatment difference: –0.4; P=0.006).
ConclusionsDeutetrabenazine treatment led to statistically and clinically significant improvements in TD symptoms based on the CGIC result, suggesting that clinicians were able to recognize the benefit in patients treated with deutetrabenazine.
Presented at: The International Congress of Parkinson’s Disease and Movement Disorders; June 4–8, 2017; Vancouver, British Columbia, Canada.
Funding AcknowledgementsThese studies were funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.