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

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.

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

CNS Spectrums ◽

10.1017/s1092852918000433 ◽

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.

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Long-Term Safety and Efficacy of Deutetrabenazine in Younger and Older Patients With Tardive Dyskinesia

CNS Spectrums ◽

10.1017/s1092852920002527 ◽

2021 ◽

Vol 26 (2) ◽

pp. 157-158

Author(s):

Martha Sajatovic ◽

Amanda Wilhelm ◽

Stacy Finkbeiner ◽

Hadas Barkay ◽

Nayla Chaijale ◽

...

Keyword(s):

Tardive Dyskinesia ◽

Older Patients ◽

Involuntary Movement ◽

Treatment Success ◽

Incidence Rates ◽

Limited Information ◽

Open Label ◽

Open Label Extension ◽

Pharmaceutical Industries ◽

Global Impression Of Change

AbstractBackgroundTardive dyskinesia (TD) is an involuntary movement disorder that is more prevalent in older patients. However, there is limited information on TD treatment for this population. In two 12-week pivotal trials (ARM-TD and AIM-TD), TD patients demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) score with deutetrabenazine versus placebo.MethodsPatients who completed ARM-TD or AIM-TD enrolled in an open-label extension (OLE) study. This post hoc analysis assessed change and percent change from baseline in AIMS score, response rates for ≥50% AIMS improvement, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety in younger (<55 years) and older (≥55 years) patients.ResultsThis analysis included 119 younger and 218 older patients enrolled in the OLE. Data presented at Week 145 (mean±SE): total deutetrabenazine dose was 39.4±1.39mg/day and 39.5±1.04mg/day in younger and older patients, respectively. Changes from baseline in AIMS score were –6.7±0.62 and –6.5±0.47, respectively (percent changes of –61.4%±4.10% and –54.6%±3.01%). The majority of younger and older patients achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%) and achieved ≥50% AIMS response (76% and 62%). Deutetrabenazine was generally well tolerated in both groups. Exposure-adjusted incidence rates (incidence/patient-years) were <0.01 and 0.02 for akathisia, 0.07 (both) for somnolence and sedation, 0.04 and 0.11 for parkinson-like events, and 0.06 and 0.09 for depression in younger and older patients, respectively.ConclusionsDeutetrabenazine treatment was associated with sustained improvements in AIMS score and was well tolerated in both younger and older TD patients.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

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Minimal Clinically Important Difference in AIMS Score Based on CGIC and PGIC in Patients With Tardive Dyskinesia Treated With Deutetrabenazine

CNS Spectrums ◽

10.1017/s1092852920002552 ◽

2021 ◽

Vol 26 (2) ◽

pp. 159-159

Author(s):

Hadas Barkay ◽

Robert A. Hauser ◽

Amanda Wilhelm ◽

Maria Wieman ◽

Mark Forrest Gordon ◽

...

Keyword(s):

Tardive Dyskinesia ◽

Minimal Clinically Important Difference ◽

Involuntary Movement ◽

Treatment Success ◽

Meaningful Improvement ◽

Clinically Important Difference ◽

Pharmaceutical Industries ◽

The Difference ◽

Global Impression Of Change ◽

Treatment Improvement

AbstractBackgroundDeutetrabenazine is FDA approved for tardive dyskinesia (TD) based on two 12-week, placebo-controlled studies evaluating safety and efficacy in patients with baseline Abnormal Involuntary Movement Scale (AIMS) score ≥6. Deutetrabenazine reduced overall AIMS scores compared with placebo in ARM-TD (–3.0 vs –1.6, P=0.019) and AIM-TD (24 mg/day, –3.2 vs –1.4, P=0.003; 36 mg/day, –3.3 vs –1.4, P=0.001). This analysis assessed Minimal Clinically Important Difference (MCID) in AIMS score in patients with TD treated with deutetrabenazine.MethodsMCID is the smallest change from baseline in AIMS score that is meaningful for patients. MCID analyses were performed based on Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) as anchors described by Hauser et al., where MCID is the difference between patients treated with deutetrabenazine who were minimally improved and patients treated with placebo who were unchanged. Additional MCID definitions were explored: difference between patients who demonstrated treatment improvement versus those who did not (Method 2); difference between patients who demonstrated treatment success versus those who did not (Method 3).Results295 patients were analyzed. Based on PGIC, the suggested MCID was –2.8. Results were similar for Method 2 (75% of patients had treatment improvement; MCID = –2.8) and Method 3 (38% of patients had treatment success; MCID = –2.6). Based on CGIC, the suggested MCID was –2.6. Results were similar for Method 2 (76% of patients had treatment improvement; MCID = –2.8) and Method 3 (41% of patients had treatment success; MCID = –3.0). Therefore, the suggested MCID for deutetrabenazine is –3.ConclusionsThe MCID for change in AIMS score based on PGIC and CGIC for deutetrabenazine was –3 regardless of the analytical method. Findings suggest an AIMS score reduction of ~3 is associated with clinically meaningful improvement in TD symptoms.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

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Randomized controlled trial of deutetrabenazine for tardive dyskinesia

Neurology ◽

10.1212/wnl.0000000000003960 ◽

2017 ◽

Vol 88 (21) ◽

pp. 2003-2010 ◽

Cited By ~ 82

Author(s):

Hubert H. Fernandez ◽

Stewart A. Factor ◽

Robert A. Hauser ◽

Joohi Jimenez-Shahed ◽

William G. Ondo ◽

...

Keyword(s):

Tardive Dyskinesia ◽

Primary Endpoint ◽

Rating Scale ◽

Involuntary Movement ◽

Controlled Trial ◽

Treatment Success ◽

Eligibility Criteria ◽

Double Blind ◽

Abnormal Movements ◽

Global Impression Of Change

Objective:To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD).Methods:One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment. Primary endpoint was the change in AIMS score from baseline to week 12. Secondary endpoints included treatment success at week 12 on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change.Results:For the primary endpoint, deutetrabenazine significantly reduced AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard error] −3.0 [0.45] vs −1.6 [0.46],p= 0.019). Treatment success on CGIC (48.2% vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs 6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs 1.7%, respectively). In addition, no worsening in parkinsonism, as measured by the Unified Parkinson's Disease Rating Scale motor subscale, was noted from baseline to week 12 in either group.Conclusions:In patients with TD, deutetrabenazine was well tolerated and significantly reduced abnormal movements.Classification of evidence:This study provides Class I evidence that in patients with TD, deutetrabenazine reduces AIMS scores.

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35 Long-term Improvements in Site-Rated Outcomes with Deutetrabenazine Treatment in Patients with Tardive Dyskinesia

CNS Spectrums ◽

10.1017/s1092852919000294 ◽

2019 ◽

Vol 24 (1) ◽

pp. 193-194

Author(s):

Karen E. Anderson ◽

David Stamler ◽

Mat D. Davis ◽

Nicholas Gross ◽

Robert A. Hauser ◽

...

Keyword(s):

New York ◽

Clinical Practice ◽

Tardive Dyskinesia ◽

Real World ◽

Treatment Success ◽

Open Label ◽

Double Blind ◽

Abnormal Movements ◽

Global Impression Of Change

AbstractBackgroundTardive dyskinesia (TD) is an often-irreversible movement disorder that may intensify the stigma of patients with psychiatric disorders and worsen quality of life. In two randomized, double-blind, placebo (PBO)-controlled, 12-week trials, ARM-TD and AIM-TD (‘parent studies’), deutetrabenazine (DTB) demonstrated statistically significant improvements in centrally read Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with PBO and was generally well tolerated.Study ObjectiveTo evaluate the long-term efficacy of DTB in an open-label safety study following double-blind treatment using site-rated efficacy measures: AIMS, the Clinical Global Impression of Change (CGIC) and the Patient Global Impression of Change (PGIC), which may be used in real-world clinical practice settings.MethodPatients with TD who completed the parent studies were eligible to enter this open-label, long-term extension (OLE) after completing the 1-week washout period and final evaluation in the blinded portion of the trial. This extension comprised a 6-week titration period followed by a long-term maintenance phase. Patients began DTB at 12mg/day, titrating up to a maximum total dose of 48mg/day based on dyskinesia control and tolerability. Efficacy endpoints included in this analysis are the change in site-rated AIMS score (items 1–7) from parent study baseline, and the proportion of patients who were “Much Improved” or “Very Much Improved” (treatment success) on the CGIC and PGIC from OLE baseline.ResultsAt the end of the parent studies (Week 12), patients treated with DTB had experienced greater mean (standard error) improvements in site-rated AIMS score (–5.0[0.40]) than patients given PBO (–3.2[0.47]). With long-term DTB treatment, both groups experienced improvements in site-rated AIMS scores (prior DTB, –7.9[0.62]; prior placebo, –6.6[0.64]) compared with parent study baseline. Similarly, at the end of the parent studies, a greater proportion of patients treated with DTB had treatment success on the CGIC (DTB, 51%; PBO, 32%) and the PGIC (DTB, 46%; PBO: 33%); whereas at Week 54 of the OLE study, treatment success on CGIC and PGIC were similar in both the CGIC (prior DTB: 66%; prior PBO: 68%) and PGIC (prior DTB: 62%; prior PBO: 62%) groups. DTB was generally well tolerated.ConclusionsPatients treated with DTB showed improvements in abnormal movements, as measured by site-rated AIMS, CGIC, and PGIC scores, which may be used in real-world clinical practice settings. These results corroborate the previously reported efficacy of DTB as observed in the 12-week, double-blind ARM-TD and AIM-TD trials, in which central raters were used to evaluate AIMS scores.Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USAFunding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

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Deutetrabenazine Reduces Severe Tardive Dyskinesia Movements in a 3-year Open-Label Extension Trial

CNS Spectrums ◽

10.1017/s1092852920002497 ◽

2021 ◽

Vol 26 (2) ◽

pp. 156-156

Author(s):

Nayla Chaijale ◽

Joseph Bona ◽

Hadas Barkay ◽

Amanda Wilhelm ◽

Mark Forrest Gordon

Keyword(s):

Tardive Dyskinesia ◽

Treatment Guidelines ◽

Involuntary Movement ◽

Open Label ◽

Percent Change ◽

Open Label Extension ◽

Pharmaceutical Industries ◽

Clinically Significant ◽

Post Hoc ◽

Lost To Follow Up

AbstractBackgroundThere are no established treatment guidelines for tardive dyskinesia (TD) based on movement severity. The 12-week ARM-TD and AIM-TD studies in TD patients with baseline Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7) ≥6 showed clinically significant improvements in AIMS score with deutetrabenazine versus placebo. Patients who completed these studies were eligible for the open-label extension (OLE) trial. This post-hoc analysis evaluated deutetrabenazine in TD patients with severe movements.MethodsSubgroups were defined by upper quartile of baseline total AIMS score (local rating). Endpoints were: change and percent change from baseline in AIMS score, and percent of patients achieving ≥50% AIMS reduction from baseline.Results337 patients were analyzed. The upper quartile of baseline total AIMS score was 14. Subgroups were defined as >14 and ≤14 at baseline, respectively (n=64 vs 273); data are presented at Week 145 (n=40 vs 120). Mean treatment duration was 880.5 and 760.8 days. Mean±SE daily doses were 41.1±1.6mg and 38.9±1.0mg. Mean±SE change from baseline in AIMS score was –11.0±0.8 versus –5.1±0.3; percent change from baseline was –60.1%±3.6% versus –55.9%±3.0%. More patients with AIMS score >14 had ≥50% AIMS reduction (73% vs 65%). Less patients discontinued (38% vs 51%); reasons included withdrawal by subject (16% vs 25%), adverse event (3% vs 11%), and lost to follow-up (6% vs 7%). Withdrawal due to lack of efficacy was uncommon (5% vs 2%).ConclusionsPatients with baseline total AIMS score >14 had clinically meaningful reductions in AIMS score, suggesting deutetrabenazine has long-term benefit in these patients.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

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Long-Term Deutetrabenazine Treatment Is Associated With Continued Improvement in Tardive Dyskinesia in the Completed 3-Year Open-Label Extension Study

CNS Spectrums ◽

10.1017/s1092852920002606 ◽

2021 ◽

Vol 26 (2) ◽

pp. 162-162

Author(s):

Robert A. Hauser ◽

Hadas Barkay ◽

Hubert H. Fernandez ◽

Stewart A. Factor ◽

Joohi Jimenez-Shahed ◽

...

Keyword(s):

Tardive Dyskinesia ◽

Involuntary Movement ◽

Treatment Success ◽

Incidence Rates ◽

Open Label ◽

Long Term Treatment ◽

Open Label Extension ◽

Pharmaceutical Industries ◽

Experienced Treatment

AbstractBackgroundThe 12-week ARM-TD and AIM-TD studies in tardive dyskinesia (TD) patients showed statistically significant improvements in TD symptoms with deutetrabenazine. The completed open-label extension (OLE) study (SD-809-C−20) evaluated long-term efficacy and safety of deutetrabenazine in TD.MethodsPatients who completed ARM-TD or AIM-TD enrolled in the OLE study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score was assessed by local site raters. Treatment success was evaluated locally as patients being “much improved” or “very much improved” on Clinical Global Impression of Change (CGIC).Results343 patients enrolled in the OLE study; 6 patients were excluded from analyses. At Week 54 (n=249; dose [mean±SE]: 38.7±0.66mg/day), mean change from baseline in AIMS score was –4.8±0.28; 66% of patients experienced treatment success. At Week 106 (n=194; dose: 39.3±0.75mg/day), mean change from baseline in AIMS score was –5.4±0.33; 65% of patients experienced treatment success. At Week 145 (n=160; dose: 39.4±0.83mg/day), mean change from baseline in AIMS score was –6.6±0.37; 73% of patients experienced treatment success. Treatment was generally well tolerated across 723 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) for akathisia/restlessness were 0.01, somnolence/sedation were 0.07, and symptoms which may represent parkinsonism or depression were 0.08 each.ConclusionsPatients who received long-term treatment with deutetrabenazine achieved sustained improvement in AIMS scores. Findings from this open-label trial with response-driven dosing suggest the possibility of increasing benefit over time.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

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Efficacy of opicapone in Parkinson’s disease patients with ‘early’ motor fluctuations: Patient and clinical global impression of change from the BIPARK-I double-blind experience

Journal of the Neurological Sciences ◽

10.1016/j.jns.2019.10.1151 ◽

2019 ◽

Vol 405 ◽

pp. 191-192

Author(s):

F. Rocha ◽

F. Stocchi ◽

A. Lees ◽

J. Ferreira ◽

W. Poewe ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Global Impression ◽

Motor Fluctuations ◽

Double Blind ◽

Global Impression Of Change

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141 The Effects of Valbenazine on Tardive Dyskinesia: Subgroup Analyses of 3 Randomized, Double-Blind, Placebo-Controlled Trials

CNS Spectrums ◽

10.1017/s1092852918000366 ◽

2018 ◽

Vol 23 (1) ◽

pp. 88-88

Author(s):

Jonathan Meyer ◽

Gary Remington ◽

Ali Norbash ◽

Joshua Burke ◽

Scott Siegert ◽

...

Keyword(s):

Tardive Dyskinesia ◽

Involuntary Movement ◽

Controlled Trials ◽

Cyp2d6 Genotype ◽

Double Blind ◽

Double Blind Placebo ◽

Score Improvement ◽

Subgroup Analyses ◽

History Of ◽

Intent To Treat

AbstractStudy ObjectivesThe approval of valbenazine (INGREZZA; VBZ) for the treatment of tardive dyskinesia (TD) in adults was based on results from double-blind, placebo (PBO)-controlled trials. These studies demonstrated the efficacy of once-daily VBZ based on intent-to-treat analyses. However, because many different types ofpatients can develop TD, subgroup analyses describing treatment outcomes by various patient factors were also conducted.MethodsData were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558), with outcomes analyzed by VBZ dose (80 mg, 40 mg) and PBO. Descriptive analyses conducted using the Abnormal Involuntary Movement Scale (AIMS) total score included: mean change from baseline to Week 6; and AIMS response, defined as 50% improvement from baseline to Week 6. Subgroups were defined as follows: age (<55 years, ≥55 years), sex (male, female), psychiatric diagnosis (schizophrenia/schizoaffective disorder, mood disorder), CYP2D6 genotype (poor metabolizer [PM], non-PM), body mass index (BMI) (<18.5, 18.5 to <25, 25 to <30, ≥30 kg/m2), concomitant antipsychotic (yes, no); type of antipsychotic (atypical, typical/both); lifetime history of suicidality (yes, no); concomitant anticholinergic (yes, no); TD duration (<7 years, ≥7 years).ResultsThe pooled population included 373 participants (VBZ 80 mg, n=101; VBZ 40 mg, n=114; PBO, n=158). Mean improvements from baseline to Week 6 in AIMS total score were greater overall with VBZ compared to PBO. Within subgroup categories, AIMS score improvement with VBZ 80 mg (recommended dose) was greater in CYP2D6 PMs (n=17; 80 mg, -6.8; 40 mg, 2.4; PBO, 0.5), participants taking no concomitant antipsychotics (n=64; 80 mg, -4.9; 40 mg, -3.0; PBO, 0.0), and overweight participants (BMI 25 to <30 kg/m2, n=115; 80 mg, -4.2; 40 mg, 2.7; PBO, -0.7). Overweight participants also had the highest AIMS response rates at Week 6 (80 mg, 57.7%; 40 mg, 31.6%; PBO, 11.8%), followed by participants taking typical/both antipsychotics (n=67; 80 mg, 57.1%; 40 mg, 20.0%; PBO, 25.0%), and those taking anticholinergics (n=126; 80 mg, 52.9%; 40 mg, 22.7%; PBO, 6.3%).ConclusionThese preliminary analyses indicate that TD improvements were generally greater with VBZ than PBO across most subgroups. However, the small sizes of some subgroups may need to be considered when interpreting results. Additional analyses within subgroup categories are ongoing and will be presented at the meeting.Funding AcknowledgementsThis study was funded by Neurocrine Biosciences, Inc.

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

CNS Spectrums ◽

10.1017/s1092852920000413 ◽

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.

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