Efficacy and Safety of MT-5199 in Subjects With Tardive Dyskinesia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of MT-5199 administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.

Official Title
-----------------
A Double-Blind, Randomized, Multicenter, Placebo-Controlled, Parallel, Fixed-Dose Study to Evaluate the Efficacy and Safety of MT-5199 for the Treatment in Patients With Tardive Dyskinesia (J-KINECT)

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

Intervention / Treatment
-----------------
* Drug: MT-5199
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have one of the following clinical diagnoses for at least 3 months prior to screening: Schizophrenia or Schizoaffective Disorder, Bipolar Disorder, or Depressive Disorders. Have a clinical diagnosis of neuroleptic-induced TD. Have moderate or severe TD. If using maintenance medication(s) for schizophrenia or schizoaffective disorder, or bipolar disorder, or depressive disorders, be on stable doses. Exclusion Criteria: Have an active, clinically significant unstable medical condition in screening period. Have a significant risk of suicidal or violent behavior. Have a known history of long QT syndrome or cardiac tachy-arrhythmia. Are currently pregnant or breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 85 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT-5199 40 mg (Double-Blind Placebo-Controlled Period)<br>MT-5199 administered as one (1) 40 mg capsule and one (1) placebo capsule, taken by mouth, every morning for 6 weeks. | Drug: MT-5199<br>* MT-5199 40 mg capsules<br>Drug: Placebo<br>* MT-5199 placebo capsules<br>|
| Experimental: MT-5199 80 mg (Double-Blind Placebo-Controlled Period)<br>Subjects randomized to the MT-5199 80 mg dose will receive MT-5199 40 mg for the first week (administered as one (1) 40 mg capsule and one (1) placebo capsule), followed by MT-5199 80 mg administered as two (2) 40 mg capsules, taken by mouth, every morning for 5 weeks. | Drug: MT-5199<br>* MT-5199 40 mg capsules<br>Drug: Placebo<br>* MT-5199 placebo capsules<br>|
| Experimental: Placebo (Double-Blind Placebo-Controlled Period)<br>Placebo administered as two (2) placebo capsules, taken by mouth, every morning for 6 weeks. | Drug: Placebo<br>* MT-5199 placebo capsules<br>|
| Experimental: MT-5199 40 mg (Double-Blind Extension Period)<br>At the end of Week 6, subjects will enter a double-blind extension period for 42 weeks. Subjects who were initially randomized to placebo will be re-randomized (1:1) to receive either MT-5199 40 mg or 80 mg and subjects initially randomized to MT-5199 will continue with their current dose. | Drug: MT-5199<br>* MT-5199 40 mg capsules<br>Drug: Placebo<br>* MT-5199 placebo capsules<br>|
| Experimental: MT-5199 80 mg (Double-Blind Extension Period)<br>At the end of Week 6, subjects will enter a double-blind extension period for 42 weeks. Subjects who were initially randomized to placebo will be re-randomized (1:1) to receive either MT-5199 40 mg or 80 mg and subjects initially randomized to MT-5199 will continue with their current dose. Subjects re-randomized to receive MT-5199 80 mg will receive 40 mg for the first week. | Drug: MT-5199<br>* MT-5199 40 mg capsules<br>Drug: Placebo<br>* MT-5199 placebo capsules<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Central Assessment) 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 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 |
| --- | --- | --- |
| Percentage of Subjects With a ≥50% Improvement From Baseline in the AIMS Total Score (Central Assessment) at Week 6 (AIMS Responder) | Percentage of AIMS responders (subjects who had at least a 50 percent reduction in AIMS score from baseline) | Week 6 | 
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Site Assessment) at Week 6 | Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by blinded 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 and Week 6 | 
| Clinical Global Impression of Change - TD (CGI-TD) Score 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 |