A Phase 3 Study of NBI-98854 for the Treatment of Tardive Dyskinesia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, and tolerability of NBI-98854 administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.

Detailed Description
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This is a Phase 3, randomized, double-blind, placebo-controlled, parallel, fixed-dose study to evaluate the efficacy, safety, and tolerability of two doses of NBI-98854 (40 mg and 80 mg) compared to placebo, administered once daily. The study design includes a double-blind, placebo-controlled treatment period for 6 weeks and a double-blind NBI-98854 treatment period for an additional 42 weeks, for a total of 48 weeks of treatment. Final follow-up assessments will be conducted 4 weeks after the last dose of the study drug.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel, Fixed-Dose Study to Assess the Efficacy, Safety, and Tolerability 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
* Drug: Placebo


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 good general health. Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol. Have a negative drug screen for amphetamines,barbiturates, benzodiazepines, 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, or 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 of screening (some exceptions allowed) Have received an investigational drug within 30 days prior to 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. Have had previous exposure with NBI-98854 or had previously participated in an NBI-98854 clinical study. 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NBI-98854 40 mg<br>NBI-98854 administered as one (1) 40 mg capsule and one (1) placebo capsule, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose. | Drug: NBI-98854<br>* NBI-98854 40 mg capsules<br>Drug: Placebo<br>* NBI-98854 placebo capsules<br>|
| Experimental: NBI-98854 80 mg<br>Subjects randomized to the NBI-98854 80 mg dose will receive NBI-98854 40 mg for the first week (administered as one (1) 40 mg capsule and one (1) placebo capsule), followed by NBI-98854 80 mg administered as two (2) 40 mg capsules, taken by mouth, every morning between 7:00am - 10:00am for 5 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose. | Drug: NBI-98854<br>* NBI-98854 40 mg capsules<br>Drug: Placebo<br>* NBI-98854 placebo capsules<br>|
| Experimental: Placebo<br>Placebo administered as two (2) placebo capsules, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and be randomized to either a 40 mg or 80 mg dose. Subjects re-randomized to receive NBI-98854 80 mg will receive 40 mg for the first week. | Drug: NBI-98854<br>* NBI-98854 40 mg capsules<br>Drug: Placebo<br>* NBI-98854 placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6 | Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by 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 and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression of Change - TD (CGI-TD) at Week 6 | Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse). | Week 6 | 
| Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Responder Analysis at Week 6 | Percentage of AIMS responders (subjects who had at least a 50 percent reduction in AIMS score from baseline) | Week 6 |