scholarly journals 123 Long-Term Outcomes with Valbenazine 40 mg/day in Adults With Tardive Dyskinesia

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 279-280
Author(s):  
Craig Chepke ◽  
Stephen R. Marder ◽  
Cynthia L. Comella ◽  
Carlos Singer ◽  
Khodayar Farahmand ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Dose Reduction ◽  
Prolonged Exposure ◽  
Involuntary Movement ◽  
Small Sample ◽  
Long Term Outcomes ◽  
Double Blind ◽  
Study Objective ◽  
40Mg Group

Abstract:Study Objective:Tardive dyskinesia (TD), a persistent and potentially disabling movement disorder, is associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine (VBZ) is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from two long-term phase 3 studies (KINECT 3 [K3], NCT02274558; KINECT 4 [K4], NCT02405091) and a rollover study (1506, NCT02736955), the long-term outcomes of once-daily VBZ on TD were examined in participants who received 40mg or had a dose reduction from 80 to 40mg.Methods:The effects of VBZ 40mg (as well as VBZ 80mg) were evaluated in the following studies: the pivotal K3 study (6 weeks double-blind, placebo controlled), the extension phase of K3 (42 additional weeks of VBZ, 4 week discontinuation), and the open-label K4 study (48 weeks of VBZ, 4 week discontinuation). Completers from K3 extension and K4 were invited to participate in 1506 (up to 72 additional weeks of VBZ or until commercial availability of VBZ). Few participants reached Week 60 (n=4) or Week 72 (n=0) in the 1506 study before termination. Analyses focused on VBZ 40mg in two populations: pooled K3/K4 (participants who received VBZ 40mg throughout K3 or K4 or who had a dose reduction [80/40mg] during K3 or K4); and 1506 (participants who received VBZ 40mg from beginning of K3 or K4 to last visit in 1506 or who had a dose reduction [80/40mg] at any time). Outcomes for the K3/K4 population included mean change from baseline (CFB) in Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48 of K3 or K4. Outcomes for the 1506 population included a Clinical Global Impression of Severity-Tardive Dyskinesia (CGIS-TD) score ≤2 (“normal, not at all ill” or “borderline ill”).Results:In the K3/K4 population, AIMS CFB to Week 48 indicated mean TD improvements in participants who received 40mg continuously (40mg, -5.7 [n=54]) and in those who had a dose reduction to 40mg (80/40mg, -6.2 [n=13]). In addition, a majority of these participants had an AIMS response after 48 weeks of treatment (40mg, 53.7%; 80/40mg, 53.8%). In the 1506 population, the percentage of participants who had a CGIS-TD score ≤2 (rating of “normal, not at all ill” or “borderline ill”) at Week 12 was 63.6% (7/11) in the 40mg group and 30.8% (4/13) in the 80/40mg group. Data from Weeks 24 to 60 of 1506 were limited by the small sample sizes (<10 participants each in 40mg or 80/40mg group at each of these visits).Conclusions:Based on these analyses and results from published studies, VBZ 40mg may be an effective long-term option for some TD patients. Dose reductions from 80 to 40mg, if necessary, did not appear to compromise long-term benefit.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

scholarly journals 151 Confirmed Safety of Deutet.rabenazine for Tardive Dyskinesia in a 3-Year Open-Label Extension Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 296-297 ◽  
Author(s):  
Hubert H. Fernandez ◽  
Hadas Barkay ◽  
Robert A. Hauser ◽  
Stewart A. Factor ◽  
Joohi Jimenez-Shahed ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Dose Reduction ◽  
Involuntary Movement ◽  
Maintenance Phase ◽  
Incidence Rates ◽  
Extension Study ◽  
Total Daily Dose ◽  
Short Term ◽  
Open Label

Abstract:Background:Deutetrabenazine (Austedo) is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The objective of this study was to evaluate the long-term safety and tolerability of deutetrabenazine in patients with TD at 3 years.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 for calculating AE frequencies. This analysis reports results up to Week 158.RESULTS:A total of 343 patients were enrolled (111 received placebo and 232 received deutetrabenazine in the parent studies). At the time of this analysis, 183 patients were still receiving treatment; 259 completed 1 year, 172 completed 2 years, and 41 completed 3 years. There were 623 patient-years of exposure. More than 40% of patients reached the maximum dose. EAIRs of AEs were comparable to or lower than those observed in the ARM-TD and AIM-TD short-term randomized trials of deutetrabenazine vs. placebo. The frequency of SAEs (EAIR 0.10) was similar to that observed with short-term placebo (0.33) and short-term deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.06), dose reduction (0.10), and dose suspension (0.05) were uncommon.CONCLUSION:These results support the safety outcomes observed in the ARM-TD and AIM-TD parent studies and the safety of deutetrabenazine for long-term use in patients with TD.Funding Acknowledgements: This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel

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

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 201-201 ◽  
Author(s):  
Hubert H. Fernandez ◽  
David Stamler ◽  
Mat D. Davis ◽  
Stewart A. Factor ◽  
Robert A. Hauser ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Dose Reduction ◽  
Term Treatment ◽  
Extension Study ◽  
Short Term ◽  
Open Label ◽  
Short Term Treatment ◽  
Study Objective ◽  
Long Term Treatment

AbstractStudy ObjectiveTo 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,USAFunding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel

scholarly journals Onset and Resolution of Key Adverse Events in Valbenazine-Treated Patients with Tardive Dyskinesia: Pooled Analyses from Two Long-Term Clinical Trials

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 151-151
Author(s):  
Stephen R. Marder ◽  
Jean-Pierre Lindenmayer ◽  
Chirag Shah ◽  
Tara Carmack ◽  
Angel S. Angelov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Tardive Dyskinesia ◽  
Suicidal Behavior ◽  
Prolonged Exposure ◽  
First Occurrence ◽  
Balance Disorder ◽  
Clinical Interest ◽  
Post Hoc

AbstractObjectiveTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).MethodsParticipants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.ResultsIn the pooled population (N=314), all AEs of potential clinical interest occurred in <10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); >85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).ConclusionsIn long-term clinical trials, the incidence of AEs of potential clinical interest was low (<10%) and most were resolved by end of treatment (>70–100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.FundingNeurocrine Biosciences, Inc.

scholarly journals Congenital Micropenis: Aetiology And Management

2021 ◽  
Author(s):  
Marianna Rita Stancampiano ◽  
Kentaro Suzuki ◽  
Stuart O’Toole ◽  
Gianni Russo ◽  
Gen Yamada ◽  
...  
Keyword(s):  
Racial Differences ◽  
Small Sample Size ◽  
Small Sample ◽  
Long Term Outcomes ◽  
Penile Length ◽  
Appearance Quality ◽  
Wide Range ◽  
The Impact

Abstract In the newborn, penile length is determined by a number of androgen dependent and independent factors. The current literature suggests that there are inter-racial differences in stretched penile length in the newborn and although congenital micropenis should be defined as a stretched penile length of less than 2.5SDS of the mean for the corresponding population and gestation, a pragmatic approach would be to evaluate all boys with a stretched penile length below 2 cm, as congenital micropenis can be a marker for a wide range of endocrine conditions. However, it remains unclear as to whether the state of micropenis, itself, is associated with any long-term consequences. There is a lack of systematic studies comparing the impact of different therapeutic options on long-term outcomes, in terms of genital appearance, quality of life and sexual satisfaction. To date, research has been hampered by a small sample size and inclusion of a wide range of heterogeneous diagnoses; for these reasons, condition specific outcomes have been difficult to compare between studies. Lastly, there is a need for a greater collaborative effort in collecting standardized data so that all real-world or experimental interventions performed at an early age can be studied systematically into adulthood.

Long-Term Outcomes and Factors Related to the Prognosis of Pure Ovarian Dysgerminoma: A Retrospective Study of 107 Cases

2021 ◽  
pp. 1-8
Author(s):  
Tianyun Xu ◽  
Fei Sun ◽  
Yanfang Li
Keyword(s):  
Retrospective Study ◽  
Survival Rate ◽  
Disease Free Survival ◽  
Small Sample ◽  
Stage I ◽  
Long Term Outcomes ◽  
Free Survival ◽  
Disease Free Survival Rate ◽  
Disease Free

<b><i>Objective:</i></b> The aim of this study was to evaluate the long-term outcomes and the factors related to patient prognosis. <b><i>Materials and Methods:</i></b> We retrospectively analyzed patients treated at the Department of Gynecology, Sun Yat-sen University Cancer Center, between January 1, 1968, and December 12, 2018. <b><i>Results:</i></b> A total of 107 patients were identified. Of all patients, 79 (73.8%) presented with stage I disease, 14 (13.1%) stage II, 13 (12.2%) stage III, and 1 (0.9%) stage IV. All patients received surgery, with 70 (65.4%) undergoing fertility-sparing surgery (FS) and 37 (34.6%) nonfertility-sparing surgery (NFS). Ninety patients received postoperative chemotherapy. Nine of the 43 cases with a lymphadenectomy had metastasis (20.9%). The median follow-up time was 132 months (range, 1–536 months). The overall 5-year and 10-year survival was 95.1% and 91.7%, respectively. The 10-year survival rate for stage I and II–IV patients was 96.1% and 79.1%, respectively (<i>p</i> = 0.008). For the patients undergoing FS and NFS, the 10-year disease-free survival rate was 82.3% and 88.0%, respectively (<i>p</i> = 0.403). The 10-year disease-free survival rate for patients with or without lymphadenectomy was 95.1% and 78.4%, respectively (<i>p</i> = 0.040), and it was 92.5% and 76.0%, respectively (<i>p</i> = 0.041), for those with or without omentectomy. Fifteen patients relapsed, and 4 of them (26.7%) had recurrence in the lymph nodes. Eleven of the 15 relapsed patients (73.3%) had been successfully salvaged. <b><i>Limitations:</i></b> As a study of a rare disease, our analysis was limited by its small sample size and the deemed disadvantage of a retrospective study. <b><i>Conclusion:</i></b> Excellent treatment results can be achieved in dysgerminoma patients who received proper treatment. Lymphadenectomy may improve patient survival. Relapsed patients can also be successfully salvaged.

scholarly journals 139 Early Response with Valbenazine and Long-Term Symptom Reduction in Patients with Tardive Dyskinesia: Post Hoc Analysis of the KINECT 3 Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 288-289
Author(s):  
Stanley N. Caroff ◽  
Jean-Pierre Lindenmayer ◽  
Stephen R. Marder ◽  
Stewart A. Factor ◽  
Khodayar Farahmand ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Early Response ◽  
Term Treatment ◽  
Score Change ◽  
Double Blind ◽  
Early Improvement ◽  
Long Term Treatment ◽  
Post Hoc ◽  
Improvement Score

Abstract:Study Objective:Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from a long-term study (KINECT 3; NCT02274558), the effects of once-daily valbenazine (40 mg, 80 mg) on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS) in participants who were early responders based on subjective measures, including patient self-report (Patient Global Impression of Change [PGIC]) or clinician judgment (Clinical Impression of Change-Tardive Dyskinesia [CGI-TD]).Methods:Data from KINECT 3 (6-week double-blind, placebo-controlled [DBPC] period; 42-week double-blind extension) were analyzed post hoc. Long-term outcomes included mean change from baseline to Week 48 in AIMS total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48. These AIMS outcomes were assessed in participants who achieved early improvement, defined as a PGIC or CGI-TD score of ≤3 (“minimally improved” or better) at Week 2 (first post-baseline visit of the DBPC period). Participants who initially received placebo were not included in the analyses.Results:In participants who received only valbenazine (40 or 80 mg) during KINECT 3 and had available Week 2 assessment, 50% (72/143) had early PGIC improvement (score ≤3) and 43% (61/142) had early CGI-TD improvement (score ≤3). Baseline characteristics were generally similar between participants who achieved early PGIC or CGI-TD improvement and those who did not. Based on available assessments at Week 48, mean AIMS total score change from baseline in participants with early PGIC improvement was similar to those who did not reach the early PGIC improvement threshold (-4.1 [n=35] vs -3.5 [n=41]). Mean AIMS total score change from baseline in participants with early CGI-TD improvement was similar to those who did not achieve early CGI-TD improvement (-4.2 [n=31] vs -3.5 [n=45]). AIMS response at Week 48 was also similar in those who achieved early PGIC and CGI-TD improvement (40% and 42%, respectively) compared to those who did not achieve early PGIC and CGI-TD improvement (39% and 38%, respectively).Conclusions:Results from this long-term valbenazine trial indicate that many participants achieved at least minimal patient- and clinician-reported improvement at Week 2. AIMS outcomes at Week 48 demonstrated long-term reductions in TD severity regardless of early response. More research is needed to understand the association between early improvement and long-term treatment effects, but early non-improvement based on subjective measures may not be predictive of long-term treatment failure.Presented:International Congress of Parkinson’s Disease and Movement Disorders; September 22-26, 2019; Nice, France.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

scholarly journals 149 Deutetrabenazine for the Treatment of Tardive Dyskinesia: Results From an Open-Label, Long-Term Study

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 92-93
Author(s):  
Karen E. Anderson ◽  
Mat D. Davis ◽  
Stewart A. Factor ◽  
Robert A. Hauser ◽  
L. Fredrik Jarskog ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Involuntary Movement ◽  
Treatment Success ◽  
Open Label ◽  
Dopamine Receptor Antagonists ◽  
Long Term Study ◽  
Patient Global Impression ◽  
Pharmaceutical Industries ◽  
Global Impression Of Change

AbstractIntroductionTardive 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.

scholarly journals 116 An Experimental Study to Assess the Professional and Social Consequences of Tardive Dyskinesia

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 275-276 ◽  
Author(s):  
Rajeev Ayyagari ◽  
Debbie Goldschmidt ◽  
Fan Mu ◽  
Stanley N. Caroff ◽  
Benjamin Carroll
Keyword(s):  
Tardive Dyskinesia ◽  
Involuntary Movement ◽  
Population Sample ◽  
Group Versus ◽  
Test Group ◽  
Categorical Variables ◽  
Control Group ◽  
Study Objective ◽  
Social Lives ◽  
The Impact

Abstract:Study Objective:Evaluate the impact of orofacial tardive dyskinesia (TD) symptoms on the professional and social lives of patients with TD.Background:TD, a movement disorder affecting the face and extremities, may arise in patients taking antipsychotics. The impact of social stigma on the professional and social lives of patients with orofacial manifestations of TD has not been thoroughly examined.Methods:This study is an experimental, randomized digital survey of a general population sample. Three component surveys were developed, corresponding to employment, dating, and friendship domains. For each domain, participants were randomized 1:1 into either a test group (who viewed a video of a scripted interview with a standardized patient actor depicting TD movements) or a control group (who viewed the same actors but without TD movements), and asked about their impressions of the video subject. Actor simulations were validated by physicians familiar with TD and rehearsed to simulate a total Abnormal Involuntary Movement Scale score between 6 and 10. Statistical comparison was made using Wilcoxon sign-rank or chi-squared tests for continuous and categorical variables, respectively.Results:A total of 800 respondents completed each survey. In all domains, respondents had more-negative perceptions of actors portraying TD movements than of the same actors without movements. Regarding employment, 34.8% fewer respondents in the test group versus the control group agreed that the actor would be suitable for client-facing jobs (P<0.001). Regarding dating, the proportions of respondents who agreed that they would like to continue talking to the actor and who would be interested in meeting them for coffee/drink were 25.0% and 27.2% lower, respectively, in the test group than in the control group (P<0.001). Regarding friendship, the proportions of respondents who rated the actor as interesting and who would be interested in friendship with them were 18.8% and 16.5% lower, respectively, in the test group than in the control group (P<0.001).Conclusions:Actors simulating orofacial TD movements were perceived to be statistically significantly less likely to move forward in a job interview, be considered as a potential romantic partner, or be a new friend. This is the first study to quantify the stigma faced by people with TD in a variety of professional and social situations.Funding Acknowledgements:This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

scholarly journals 134 Improvements in Clinical Global Impression of Change With Deutetrabenazine Treatment in Tardive Dyskinesia From the ARM-TD and AIM-TD Studies

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 84-84
Author(s):  
Hubert H. Fernandez ◽  
Mat D. Davis ◽  
Stewart A. Factor ◽  
Robert A. Hauser ◽  
L. Fredrik Jarskog ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Clinical Global Impression ◽  
Involuntary Movement ◽  
Treatment Success ◽  
Body Region ◽  
Double Blind ◽  
Categorical Analysis ◽  
Pharmaceutical Industries ◽  
Clinically Significant ◽  
Global Impression Of Change

AbstractIntroductionTardive 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.

scholarly journals 158 Long-Term Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia: Results From an Open-Label, Long-Term Study

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 97-97
Author(s):  
Karen E. Anderson ◽  
Mat D. Davis ◽  
Stewart A. Factor ◽  
Robert A. Hauser ◽  
L. Fredrik Jarskog ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Involuntary Movement ◽  
Incidence Rates ◽  
Extension Study ◽  
Total Daily Dose ◽  
Open Label ◽  
Long Term Study ◽  
Long Term Treatment ◽  
Pharmaceutical Industries

AbstractIntroductionIn 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.

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