Bipolar Disorder, Major Depressive Disorder, Schizoaffective Disorder, Schizophrenia, Tardive Dyskinesia
Conditions
Brief summary
This study will evaluate the effectiveness of valbenazine on patient- and clinician-reported outcomes assessing health-related quality of life, functioning, and treatment effect in participants with tardive dyskinesia (TD) who are receiving valbenazine for up to 24 weeks.
Interventions
DRUGValbenazine
Valbenazine capsules for oral administration
Sponsors
Neurocrine Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * At least 18 years of age * Have one of the following clinical diagnoses: schizophrenia or schizoaffective disorder, bipolar disorder, or major depressive disorder * Have a clinical diagnosis of neuroleptic-induced TD * Medication(s) for schizophrenia or schizoaffective disorder, bipolar disorder, or major depressive disorder and other protocol-allowed concurrent medications must be at a stable dose and expected to remain stable during the study * Participants must be outpatients and have a stable psychiatric status Key
Exclusion criteria
* Have comorbid abnormal involuntary movement(s) (for example, Parkinsonism, akathisia) that is more prominent than TD * Have an active, clinically significant unstable medical condition in the judgement of the investigator, or have any laboratory value outside the normal range that is considered by the investigator to be clinically significant at the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Tardive Dyskinesia Impact Scale (TDIS) Total Score at Week 24 | Baseline, Week 24 | The TDIS assesses the impact of impairment and disability associated with dyskinesia. It defines impact of tardive dyskinesia (TD) in terms of 6 scales: Mouth/Throat Function (3 items), Dexterity (2 items), Mobility (2 items), Pain (1 item), Emotional (2 items), and Social (1 item). Each item measured the impact of dyskinetic movements in terms of difficulty or frequency over the last 7 days on a 5-point scale, with scores ranging from 0 to 4. Response options for the difficulty items ranged from not at all (0) to extremely (4); those for the frequency items ranged from never (0) to all of the time (4). The TDIS total score was the sum of the scores of TDIS Items 1 to 11. Total scores ranged from 0 to 44, with higher scores representing greater TD impact. |
| Change From Baseline in the Sheehan Disability Scale (SDS) Items 1, 2, and 3 Score at Week 24 | Baseline, Week 24 | The SDS included 3 self-rated items designed to measure how work, social life, and family life are impaired by current psychiatric symptoms. Each item includes an 11-point analog scale that uses visual-spatial, numeric, and verbal descriptive anchors to represent the degree of disruption from 0 (none at all) to 10 (extremely). Participants who had not worked for pay or attended school in the previous 7 days for reasons unrelated to TD did not respond to Item 1 and were therefore excluded from the analysis of that item. |
| Change From Baseline in the Euro Quality of Life Visual Analogue Scale (EQ-VAS) Score at Week 24 | Baseline, Week 24 | Participants rated their overall health on a 0 to 100 hash-marked, vertical EQ-VAS where 0 represents 'The worst health you can imagine' and 100 represents 'The best health you can imagine.' An increase from baseline indicates an increase in overall health. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change (PGI-C) Score at Week 24 | Week 24 | Participants rated the change in their TD symptoms from the initiation of study treatment dosing by choosing one of 7 responses (1=very much improved, 2=much improved, 3=minimally improved, 4=not changed, 5=minimally worse, 6=much worse, and 7=very much worse). Number of participants with PGI-C score responses are reported. |
| Change From Baseline in the Clinical Global Impression of Severity - Tardive Dyskinesia (CGI-TD-S) Score at Week 24 | Baseline, Week 24 | The CGI-TD-S is based on a 7-point scale (range; 1=normal, not at all ill to 7=among the most extremely ill patients), was used to rate the overall global severity of TD. |
| Change From Baseline in the Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score at Week 24 | Baseline, Week 24 | The AIMS dyskinesia total score was defined as the sum of the scores of AIMS items 1 through 7. The scores for each item ranged from 0 (no dyskinesia) to 4 (severe dyskinesia). If any of the seven items had a missing value, the total score for that participant/visit was set equal to missing. The AIMS dyskinesia total score can therefore range from 0 to 28, with higher scores indicating greater severity. |
Countries
United States
Participant flow
Pre-assignment details
Results are reported for the overall population as a single arm irrespective of dose, as pre-specified in the protocol. Individual participants could receive different dose levels over the duration of the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Valbenazine Participants received valbenazine oral capsules qd at a dose of either 40 mg, 60 mg or 80 mg for up to 24 weeks. | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other Than Specified | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Valbenazine |
|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 11.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 17 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 38 Participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 59 |
| other Total, other adverse events | 6 / 59 |
| serious Total, serious adverse events | 6 / 59 |
Outcome results
Primary
Change From Baseline in the Euro Quality of Life Visual Analogue Scale (EQ-VAS) Score at Week 24
Participants rated their overall health on a 0 to 100 hash-marked, vertical EQ-VAS where 0 represents 'The worst health you can imagine' and 100 represents 'The best health you can imagine.' An increase from baseline indicates an increase in overall health.
Time frame: Baseline, Week 24
Population: The Full Analysis Set included all enrolled participants with at least one baseline efficacy data point for any measure and at least one postbaseline efficacy data point for any measure. Here, Overall Number of Participants Analyzed = the number of participants evaluable at the timepoint assessed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valbenazine | Change From Baseline in the Euro Quality of Life Visual Analogue Scale (EQ-VAS) Score at Week 24 | 13.1 score on a scale |
Primary
Change From Baseline in the Sheehan Disability Scale (SDS) Items 1, 2, and 3 Score at Week 24
The SDS included 3 self-rated items designed to measure how work, social life, and family life are impaired by current psychiatric symptoms. Each item includes an 11-point analog scale that uses visual-spatial, numeric, and verbal descriptive anchors to represent the degree of disruption from 0 (none at all) to 10 (extremely). Participants who had not worked for pay or attended school in the previous 7 days for reasons unrelated to TD did not respond to Item 1 and were therefore excluded from the analysis of that item.
Time frame: Baseline, Week 24
Population: The Full Analysis Set included all enrolled participants with at least one baseline efficacy data point for any measure and at least one postbaseline efficacy data point for any measure. Here, Overall Number of Participants Analyzed = the number of participants evaluable at the timepoint assessed. Number Analyzed = participants evaluable for specified SDS item.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Valbenazine | Change From Baseline in the Sheehan Disability Scale (SDS) Items 1, 2, and 3 Score at Week 24 | Item 1: Work/School Impairment | -1.2 score on a scale |
| Valbenazine | Change From Baseline in the Sheehan Disability Scale (SDS) Items 1, 2, and 3 Score at Week 24 | Item 2: Social Life Impairment | -2.3 score on a scale |
| Valbenazine | Change From Baseline in the Sheehan Disability Scale (SDS) Items 1, 2, and 3 Score at Week 24 | Item 3: Family Life/Home Responsibilities | -1.6 score on a scale |
Primary
Change From Baseline in the Tardive Dyskinesia Impact Scale (TDIS) Total Score at Week 24
The TDIS assesses the impact of impairment and disability associated with dyskinesia. It defines impact of tardive dyskinesia (TD) in terms of 6 scales: Mouth/Throat Function (3 items), Dexterity (2 items), Mobility (2 items), Pain (1 item), Emotional (2 items), and Social (1 item). Each item measured the impact of dyskinetic movements in terms of difficulty or frequency over the last 7 days on a 5-point scale, with scores ranging from 0 to 4. Response options for the difficulty items ranged from not at all (0) to extremely (4); those for the frequency items ranged from never (0) to all of the time (4). The TDIS total score was the sum of the scores of TDIS Items 1 to 11. Total scores ranged from 0 to 44, with higher scores representing greater TD impact.
Time frame: Baseline, Week 24
Population: The Full Analysis Set included all enrolled participants with at least one baseline efficacy data point for any measure and at least one postbaseline efficacy data point for any measure. Here, Overall Number of Participants Analyzed = the number of participants evaluable at the timepoint assessed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valbenazine | Change From Baseline in the Tardive Dyskinesia Impact Scale (TDIS) Total Score at Week 24 | -8.0 score on a scale |
Secondary
Change From Baseline in the Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score at Week 24
The AIMS dyskinesia total score was defined as the sum of the scores of AIMS items 1 through 7. The scores for each item ranged from 0 (no dyskinesia) to 4 (severe dyskinesia). If any of the seven items had a missing value, the total score for that participant/visit was set equal to missing. The AIMS dyskinesia total score can therefore range from 0 to 28, with higher scores indicating greater severity.
Time frame: Baseline, Week 24
Population: The Full Analysis Set included all enrolled participants with at least one baseline efficacy data point for any measure and at least one postbaseline efficacy data point for any measure. Here, Overall Number of Participants Analyzed = the number of participants evaluable at the timepoint assessed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valbenazine | Change From Baseline in the Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score at Week 24 | -6.8 score on a scale |
Secondary
Change From Baseline in the Clinical Global Impression of Severity - Tardive Dyskinesia (CGI-TD-S) Score at Week 24
The CGI-TD-S is based on a 7-point scale (range; 1=normal, not at all ill to 7=among the most extremely ill patients), was used to rate the overall global severity of TD.
Time frame: Baseline, Week 24
Population: The Full Analysis Set included all enrolled participants with at least one baseline efficacy data point for any measure and at least one postbaseline efficacy data point for any measure. Here, Overall Number of Participants Analyzed = the number of participants evaluable at the timepoint assessed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valbenazine | Change From Baseline in the Clinical Global Impression of Severity - Tardive Dyskinesia (CGI-TD-S) Score at Week 24 | -1.47 score on a scale |
Secondary
Patient Global Impression of Change (PGI-C) Score at Week 24
Participants rated the change in their TD symptoms from the initiation of study treatment dosing by choosing one of 7 responses (1=very much improved, 2=much improved, 3=minimally improved, 4=not changed, 5=minimally worse, 6=much worse, and 7=very much worse). Number of participants with PGI-C score responses are reported.
Time frame: Week 24
Population: The Full Analysis Set included all enrolled participants with at least one baseline efficacy data point for any measure and at least one postbaseline efficacy data point for any measure. Here, Overall Number of Participants Analyzed = the number of participants evaluable at the timepoint assessed.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Valbenazine | Patient Global Impression of Change (PGI-C) Score at Week 24 | 3 = Minimally Improved | 10 Participants |
| Valbenazine | Patient Global Impression of Change (PGI-C) Score at Week 24 | 4 = Not Changed | 2 Participants |
| Valbenazine | Patient Global Impression of Change (PGI-C) Score at Week 24 | 5 = Minimal Worse | 1 Participants |
| Valbenazine | Patient Global Impression of Change (PGI-C) Score at Week 24 | 6 = Much Worse | 0 Participants |
| Valbenazine | Patient Global Impression of Change (PGI-C) Score at Week 24 | 7 = Very Much Worse | 0 Participants |
| Valbenazine | Patient Global Impression of Change (PGI-C) Score at Week 24 | 1 = Very Much Improved | 13 Participants |
| Valbenazine | Patient Global Impression of Change (PGI-C) Score at Week 24 | 2 = Much Improved | 19 Participants |