Efficacy and Safety of NBI-98854 in Subjects With Tardive Dyskinesia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and efficacy of three doses (12.5, 25, and 50 mg) of NBI-98854 for the treatment of the symptoms of tardive dyskinesia (TD) in subjects with schizophrenia or schizoaffective disorder.

Detailed Description
-----------------
This is a Phase 2, open-label, dose titration study to assess the efficacy and safety of three once daily (q.d.) doses (12.5, 25, and 50 mg) of NBI-98854 administered once daily for up to 12 days consisting of three treatment periods of 4 days each (Periods 1, 2, and 3). The starting dose will be 12.5 mg q.d. (Period 1), and this dose will be escalated to 25 mg q.d. (Period 2) and then to 50 mg q.d. (Period 3) based upon each subject's ability to tolerate NBI-98854. Progression to the next dose level will be based upon the subject's ability to tolerate the previous dose and the Investigator's review of adverse events and safety data. For subjects who do not tolerate a dose increase, the dose may be decreased to the dose that was previously administered (i.e., 25 mg to 12.5 mg, 50 mg to 25 mg) and continued at that dose for the remainder of the study treatment. Up to 10 medically stable subjects with schizophrenia or schizoaffective disorder who have moderate or severe symptoms of TD will be enrolled as outpatients.

Official Title
-----------------
A Phase 2, Open-Label, Dose Titration Study to Evaluate the Efficacy and Safety of NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder

Conditions
-----------------
Tardive Dyskinesia

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females (non-childbearing potential) aged 18 to 65 years (both inclusive). Have moderate or severe Tardive Dyskinesia symptoms (Total AIMS score of at least 9) Have a clinical diagnosis of schizophrenia or schizoaffective disorder. Receiving a stable dose of antipsychotic medication for a minimum of 30 days or have stable psychiatric status. Doses of concurrent medications and the conditions being treated have been stable for a minimum of 30 days and expected to remain stable during the study. Are in good general health and expected to complete the clinical study as designed. Have a body mass index (BMI) of 18 to 38 kg/m^2. 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 (30 days) prior to screening. Have a history of substance dependence or substance (drug) or alcohol abuse within the 3 months before study start. Have a known history of neuroleptic malignant syndrome. Have a significant risk of suicidal or violent behavior. Receiving medication for the treatment of Tardive Dyskinesia Receiving any excluded concomitant medication as specified in the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: NBI-98854<br>Open-label, dose titration of active drug | Drug: NBI-98854<br>* powder in bottle, prepared doses at 12.5, 25, and 50 mg q.d. administered for up to 12 days consisting of three treatment periods of 4 days each<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Tardive Dyskinesia symptoms | Abnormal Involuntary Movements Scale (AIMS) and Clinical Global Impression - Global Improvement of TD (CGI-TD) scale | 19 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events following dosing with NBI-98854 | Outcome assessment includes monitoring of: Adverse events Clinical laboratory tests Vital signs Physical examinations 12-lead electrocardiogram (ECG) | 19 days | 
| Evaluate pharmacokinetics of three doses of NBI-98854 | Blood samples will be collected and analyzed to evaluate drug and metabolite plasma concentrations. | 19 days |