Safety and Tolerability Study of NBI-98854 for the Treatment of Tardive Dyskinesia

Study Overview
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Brief Summary
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Phase 3, open-label, study to evaluate the safety and tolerability of NBI-98854 administered once daily (qd) for a total of 48 weeks of treatment. This study will enroll approximately 150 medically stable male and female subjects with clinical diagnoses of schizophrenia or schizoaffective disorder with neuroleptic-induced TD or mood disorder with neuroleptic-induced TD.

Official Title
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A Phase 3, Open-Label, Safety and Tolerability Study of NBI-98854 for the Treatment of Tardive Dyskinesia

Conditions
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Tardive Dyskinesia

Intervention / Treatment
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* Drug: NBI-98854


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. Female subjects must not be pregnant. Have one of the following clinical diagnoses for at least 3 months prior to screening: Schizophrenia or Schizoaffective Disorder, or Mood Disorder Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months prior to screening. Have moderate or severe TD If using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder, be on stable doses. Be in general good health. Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol. Have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids. Exclusion Criteria Have an active, clinically significant unstable medical condition within 1 month prior to screening. Have a known history of substance dependence, substance (drug) or alcohol abuse. Have a significant risk of suicidal or violent behavior. Have a known history of neuroleptic malignant syndrome. Have a known history of long QT syndrome or cardiac tachy-arrhythmia. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed). Have received an investigational drug within 30 days before screening 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 tetrabenazine. Are currently pregnant or breastfeeding.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Group 1<br>Fixed dose of NBI-98854 administered once daily for 48 weeks | Drug: NBI-98854<br> <br> |
| Experimental: Dose Group 2<br>Fixed dose of NBI-98854 administered once daily up to 48 weeks | Drug: NBI-98854<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Monitored for Long-Term Safety of Valbenazine | Number of participants monitored for long-term safety through reporting of treatment-emergent adverse events and monitoring of vital signs, clinical laboratory values, and ECG. Summaries of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 48; On-site AIMS Raters | Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by On-Site AIMS video raters. The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity. | Baseline and Week 48 | 
| Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; Central AIMS Video Raters | Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by the blinded, Central AIMS Video Raters. The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity. | Baseline, Change from Baseline at Week 8, and Change from Baseline at Week 52 | 
| Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; On-Site AIMS Raters | Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by On-Site AIMS raters. The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity. | Baseline, Change from Baseline at Week 8, and Change from Baseline at Week 52 | 
| Clinical Global Impression - Global Improvement of Tardive Dyskinesia (CGI-TD) at Week 48 | Clinician's perspective of the participant's overall improvement of TD symptoms since initiation of study drug dosing. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse). | Week 48 |