NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder

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 two doses (12.5 and 50 mg) of NBI-98854 administered once daily (q.d.) for the treatment of tardive dyskinesia in subjects with schizophrenia or schizoaffective disorder.

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Two-Period Cross-Over Study to Evaluate the Efficacy and Safety of NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder

Conditions
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Tardive Dyskinesia

Intervention / Treatment
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* Drug: NBI-98854
* Drug: NBI-98854
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a clinical diagnosis of schizophrenia or schizoaffective disorder and a clinical diagnosis of neuroleptic-induced tardive dyskinesia as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), 333.82 (see Appendix 17.1) for at least 3 months prior to screening. Be receiving a stable dose of antipsychotic medication for a minimum of 30 days before study start. Subjects who are not using antipsychotic medication must have stable psychiatric status. Have the doses of concurrent medications and the conditions being treated be stable for a minimum of 30 days before study start and be expected to remain stable during the study. Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal birth control during the study. Female subjects must not be pregnant. Be in good general health and expected to complete the clinical study as designed. Have a body mass index (BMI) of 18 to 38 kg/m2 (both inclusive). Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol. Have a negative urine drug screen (negative for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids) at screening and study start, except for any subject receiving a stable dose of benzodiazepine. Have a negative alcohol breath test at screening and study start. Exclusion Criteria: Have an active clinically significant unstable medical condition within 1 month (30 days) prior to screening. Have a history of substance dependence or substance (drug) or alcohol abuse within the 3 months before study start(nicotine and caffeine dependence are not exclusionary). Have a known history of neuroleptic malignant syndrome. Have a significant risk of suicidal or violent behavior. Receiving any excluded concomitant medication such as reserpine, metoclopramide, stimulants, or tetrabenazine Receiving medication for the treatment of tardive dyskinesia. Have a positive human immunodeficiency virus antibody, (HIV-Ab), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody result at screening or have a history of positive result. 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 an allergy, hypersensitivity, or intolerance to tetrabenazine. Have had previous exposure with NBI-98854.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NBI-98854 12.5 mg<br>During the Cross-Over Study, subjects will be randomly assigned to receive one of the following treatment sequences: Sequence 1: Placebo once daily dose for Days 1-14 and 12.5 mg NBI-98854 once daily dose for Days 15-28. Sequence 2: 12.5 mg NBI-98854 once daily dose for Days 1-14 and placebo once daily dose for Days 15-28. | Drug: NBI-98854<br>* 12.5 mg powder in bottle once daily for 14 days<br>Drug: Placebo<br>* Solution containing no active substance<br>|
| Experimental: NBI-98854 50 mg<br>During the Cross-Over Study, subjects will be randomly assigned to receive one of the following treatment sequences: Sequence 3: Placebo once daily dose for Days 1-14 and 50 mg NBI-98854 once daily dose for Days 15-28. Sequence 4: 50 mg NBI-98854 once daily dose for Days 1-14 and placebo once daily dose for Days 15-28. | Drug: NBI-98854<br>* 50 mg powder in bottle once daily for 14 days<br>Drug: Placebo<br>* Solution containing no active substance<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 | 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. | Day 15 and 29, averaged | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Global Improvement of TD (CGI-TD) | 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). | Day 15 and 29, averaged |