Tardive Dyskinesia
Conditions
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.
Interventions
DRUGMT-5199
MT-5199 40 mg capsules
DRUGPlacebo
MT-5199 placebo capsules
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Central Assessment) at Week 6 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With a ≥50% Improvement From Baseline in the AIMS Total Score (Central Assessment) at Week 6 (AIMS Responder) | Week 6 | Percentage of AIMS responders (subjects who had at least a 50 percent reduction in AIMS score from baseline) |
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Site Assessment) at Week 6 | Baseline and 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. |
| Clinical Global Impression of Change - TD (CGI-TD) Score at Week 6 | 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). |
Countries
Japan
Participant flow
Recruitment details
This study enrolled schizophrenia/schizoaffective disorder subject with tardive dyskinesia (TD), or bipolar disorder/depressive disorder with TD from 100 centers in Japan.The last patient completed in September 2020.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Double-Blind Placebo-Controlled Period) Subjects received Placebo capsule (matching MT-5199 capsules) once daily for 6 weeks. | 84 |
| MT-5199 40 mg (Double-Blind Placebo-Controlled Period) Subjects received MT-5199 40mg capsule once daily for 6 weeks. | 85 |
| MT-5199 80 mg (Double-Blind Placebo-Controlled Period) Subjects received MT-5199 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks. | 84 |
| Total | 253 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Double-Blind Extension Period | Adverse Event | 0 | 0 | 0 | 15 | 18 |
| Double-Blind Extension Period | Death | 0 | 0 | 0 | 3 | 4 |
| Double-Blind Extension Period | Physician Decision | 0 | 0 | 0 | 3 | 1 |
| Double-Blind Extension Period | Withdrawal by Subject | 0 | 0 | 0 | 24 | 26 |
| Double-Blind Placebo-Controlled Period | Adverse Event | 3 | 5 | 14 | 0 | 0 |
| Double-Blind Placebo-Controlled Period | Incorrect allocation | 0 | 0 | 1 | 0 | 0 |
| Double-Blind Placebo-Controlled Period | Physician Decision | 0 | 2 | 0 | 0 | 0 |
| Double-Blind Placebo-Controlled Period | Withdrawal by Subject | 2 | 8 | 10 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo (Double-Blind Placebo-Controlled Period) | MT-5199 40 mg (Double-Blind Placebo-Controlled Period) | MT-5199 80 mg (Double-Blind Placebo-Controlled Period) | Total |
|---|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 13.4 | 58.6 years STANDARD_DEVIATION 14 | 58.0 years STANDARD_DEVIATION 13.8 | 58.9 years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 85 Participants | 84 Participants | 253 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Japanese | 84 Participants | 85 Participants | 84 Participants | 253 Participants |
| Race/Ethnicity, Customized Non-Japanese | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 48 Participants | 45 Participants | 33 Participants | 126 Participants |
| Sex: Female, Male Male | 36 Participants | 40 Participants | 51 Participants | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 85 | 0 / 84 | 3 / 108 | 4 / 95 |
| other Total, other adverse events | 15 / 84 | 30 / 85 | 44 / 84 | 71 / 108 | 69 / 95 |
| serious Total, serious adverse events | 1 / 84 | 4 / 85 | 1 / 84 | 15 / 108 | 15 / 95 |
Outcome results
Primary
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.
Time frame: Baseline and Week 6
Population: The analysis population (80 in the placebo, 68 in the MT-5199 40 mg, and 57 in the MT-5199 80 mg) consisted of subjects who satisfy all of the following conditions:~* Subjects in the ITT analysis set~* Subjects for whom the Week 6 AIMS total score (central assessment) is available
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo (Double-Blind Placebo-Controlled Period) | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Central Assessment) at Week 6 | -0.1 units on a scale |
| MT-5199 40 mg (Double-Blind Placebo-Controlled Period) | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Central Assessment) at Week 6 | -2.3 units on a scale |
| MT-5199 80 mg (Double-Blind Placebo-Controlled Period) | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Central Assessment) at Week 6 | -3.7 units on a scale |
Comparison: Control for multiplicity was accomplished through the a fixed-sequence testing procedure for Week 6 outcomes:~* AIMS dyskinesia total score mean change from baseline (CFB): MT-5199 80 mg vs. placebo.~* AIMS: MT-5199 40 mg vs. PBO. For a test result in the above list to be considered statistically significant, all of the test results higher in the list must have been significant at the 0.05 level of significance.p-value: <0.00195% CI: [-4.5, -2.6]Mixed-effect Model Repeated Measures
p-value: <0.00195% CI: [-3, -1.3]Mixed-effect Model Repeated Measures
Secondary
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.
Time frame: Baseline and Week 6
Population: The analysis population (80 in the placebo, 68 in the MT-5199 40 mg, and 57 in the MT-5199 80 mg) consisted of subjects who satisfy all of the following conditions:~* Subjects in the ITT analysis set~* Subjects for whom the Week 6 AIMS total score (site assessment) is available
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo (Double-Blind Placebo-Controlled Period) | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Site Assessment) at Week 6 | -2.3 units on a scale |
| MT-5199 40 mg (Double-Blind Placebo-Controlled Period) | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Site Assessment) at Week 6 | -3.8 units on a scale |
| MT-5199 80 mg (Double-Blind Placebo-Controlled Period) | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score (Site Assessment) at Week 6 | -4.7 units on a scale |
p-value: 0.01395% CI: [-2.7, -0.3]Mixed-effect Model Repeated Measures
p-value: <0.00195% CI: [-3.5, -1.1]Mixed-effect Model Repeated Measures
Secondary
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).
Time frame: Week 6
Population: The analysis population (80 in the placebo, 70 in the MT-5199 40 mg, and 60 in the MT-5199 80 mg) consisted of subjects who satisfy all of the following conditions:~* Subjects in the ITT analysis set~* Subjects for whom the Week 6 CGI-TD score is available
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo (Double-Blind Placebo-Controlled Period) | Clinical Global Impression of Change - TD (CGI-TD) Score at Week 6 | 3.4 units on a scale |
| MT-5199 40 mg (Double-Blind Placebo-Controlled Period) | Clinical Global Impression of Change - TD (CGI-TD) Score at Week 6 | 3.0 units on a scale |
| MT-5199 80 mg (Double-Blind Placebo-Controlled Period) | Clinical Global Impression of Change - TD (CGI-TD) Score at Week 6 | 2.8 units on a scale |
p-value: 0.02195% CI: [-0.7, -0.1]ANOVA
p-value: <0.00195% CI: [-1, -0.3]ANOVA
Secondary
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)
Time frame: Week 6
Population: The analysis population (78 in the placebo, 67 in the MT-5199 40 mg, and 53 in the MT-5199 80 mg) consisted of subjects who satisfy all of the following conditions:~* Subjects in the ITT analysis set~* Subjects for whom the Week 6 AIMS total score (central assessment) is available and the baseline AIMS total score (central assessment) is not zero
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Double-Blind Placebo-Controlled Period) | Percentage of Subjects With a ≥50% Improvement From Baseline in the AIMS Total Score (Central Assessment) at Week 6 (AIMS Responder) | 10.3 percentage of AIMS responders |
| MT-5199 40 mg (Double-Blind Placebo-Controlled Period) | Percentage of Subjects With a ≥50% Improvement From Baseline in the AIMS Total Score (Central Assessment) at Week 6 (AIMS Responder) | 23.9 percentage of AIMS responders |
| MT-5199 80 mg (Double-Blind Placebo-Controlled Period) | Percentage of Subjects With a ≥50% Improvement From Baseline in the AIMS Total Score (Central Assessment) at Week 6 (AIMS Responder) | 47.2 percentage of AIMS responders |
p-value: 0.027Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel