Persistence of Effect and Safety of Valbenazine for the Treatment of Tardive Dyskinesia

Study Overview
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Brief Summary
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This is a Phase 4, randomized, double-blind, placebo-controlled study to evaluate the persistence of effect of valbenazine 40 mg and 80 mg.

Official Title
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A Phase 4, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study to Evaluate the Persistence of Effect and Safety of Valbenazine for the Treatment of Tardive Dyskinesia

Conditions
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Tardive Dyskinesia (TD)

Intervention / Treatment
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* Drug: Valbenazine
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment, and follow-up periods of the study. Have one of the following clinical diagnoses for at least 3 months before screening: Schizophrenia, Schizoaffective Disorder, or Mood Disorder Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months before screening. Be on stable doses if using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder. Subjects with bipolar disorder must be on stable doses of a mood stabilizer. Be in general good health. Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol. Exclusion Criteria: Have an active, clinically significant unstable medical condition within 1 month before screening. Have a known history of substance (drug) dependence, or substance or alcohol abuse. Have a significant risk of suicidal or violent behavior. Have been hospitalized for psychiatric disorder within 6 months before Day 1. Have a known history of neuroleptic malignant syndrome. Have a known history of long QT syndrome or cardiac arrhythmia. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed). Are currently taking tetrabenazine or deutetrabenazine, or have used valbenazine (INGREZA) within 30 days of screening. Have received an investigational drug within 30 days before Day 1 or plan to use an investigational drug (other than NBI-98854) during the study. Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline. Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors (eg, tetrabenazine, deutetrabenazine). Are currently pregnant or breastfeeding. Have HIV or hepatitis B.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label Valbenazine<br>Participants received valbenazine 40 mg once daily for 1 week, then 80 mg once daily for the remainder of the 8-week open label period. | Drug: Valbenazine<br>* vesicular monoamine transporter 2 (VMAT2) inhibitor<br>* Other names: Ingrezza, NBI-98854;|
| Placebo Comparator: Placebo-controlled Placebo<br>Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. | Drug: Placebo oral capsule<br>* non-active dosage form<br>|
| Experimental: Placebo-controlled Valbenazine<br>Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks. | Drug: Valbenazine<br>* vesicular monoamine transporter 2 (VMAT2) inhibitor<br>* Other names: Ingrezza, NBI-98854;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Randomization (Week 8) in Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score at Week 16 | The AIMS rates 10 items of involuntary movement, each item ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Items assess facial, oral, extremity, and trunk movements, as well as self-awareness of abnormal movements. The AIMS Dyskinesia Total Score is the sum of items 1-7 and ranges from 0 to 28, with higher scores indicating more severe dyskinesia. Least-squares mean were estimated using a mixed-effects model for repeated measures. | Week 8, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Health State Index Score at Week 16 | The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The health state index score is based on the results of the individual health profiles using the United States value set and ranges from -0.573 to 1.0, with higher scores indicating higher health utility. | Baseline, Week 16 | 
| Change From Baseline in the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) at Week 16 | The EQ-5D-5L assesses general health-related quality of life. The second portion of the scale is a self-perceived health score assessed using a VAS that ranges from 0 (the worst imaginable health) to 100 (the best imaginable health). | Baseline, Week 16 |