Trial Outcomes & Findings for Persistence of Effect and Safety of Valbenazine for the Treatment of Tardive Dyskinesia (NCT NCT03891862)
NCT ID: NCT03891862
Last Updated: 2021-04-20
Results Overview
The AIMS rates 10 items of involuntary movement, each item ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Items assess facial, oral, extremity, and trunk movements, as well as self-awareness of abnormal movements. The AIMS Dyskinesia Total Score is the sum of items 1-7 and ranges from 0 to 28, with higher scores indicating more severe dyskinesia. Least-squares mean were estimated using a mixed-effects model for repeated measures.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
135 participants
Primary outcome timeframe
Week 8, Week 16
Results posted on
2021-04-20
Participant Flow
The study enrolled male and female participants, 18 to 85 years of age, from 28 centers in the United States. Participants must have clinical diagnoses of schizophrenia or schizoaffective disorder with neuroleptic-induced tardive dyskinesia (TD) or mood disorder with neuroleptic-induced TD and have moderate or severe TD as assessed by an external Abnormal Involuntary Movement Scale (AIMS) Reviewer. The first and last participant was enrolled on 18 March 2019 and 3 September 2019, respectively.
After receiving valbenazine 40 mg for the first week followed by valbenazine 80 mg for 7 weeks during the open-label period, participants were randomly assigned to either placebo or to continue to receive valbenazine 80 mg.
Participant milestones
| Measure |
Open-label Valbenazine
Participants received valbenazine 40 mg once daily for 1 week, then 80 mg once daily for the remainder of the 8-week open label period.
|
Placebo-controlled Placebo
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Placebo-controlled Valbenazine
Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
|---|---|---|---|
|
Open-label Period
STARTED
|
135
|
0
|
0
|
|
Open-label Period
Safety Analysis Set
|
132
|
0
|
0
|
|
Open-label Period
COMPLETED
|
119
|
0
|
0
|
|
Open-label Period
NOT COMPLETED
|
16
|
0
|
0
|
|
Placebo-controlled Period and Follow-up
STARTED
|
0
|
59
|
59
|
|
Placebo-controlled Period and Follow-up
Persistence of Effect Analysis Set
|
0
|
58
|
59
|
|
Placebo-controlled Period and Follow-up
Completed Placebo-controlled Period
|
0
|
53
|
56
|
|
Placebo-controlled Period and Follow-up
COMPLETED
|
0
|
53
|
55
|
|
Placebo-controlled Period and Follow-up
NOT COMPLETED
|
0
|
6
|
4
|
Reasons for withdrawal
| Measure |
Open-label Valbenazine
Participants received valbenazine 40 mg once daily for 1 week, then 80 mg once daily for the remainder of the 8-week open label period.
|
Placebo-controlled Placebo
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Placebo-controlled Valbenazine
Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
|---|---|---|---|
|
Open-label Period
Adverse Event
|
2
|
0
|
0
|
|
Open-label Period
Protocol Violation
|
5
|
0
|
0
|
|
Open-label Period
Withdrawal by Subject
|
6
|
0
|
0
|
|
Open-label Period
Death
|
1
|
0
|
0
|
|
Open-label Period
Lost to Follow-up
|
2
|
0
|
0
|
|
Placebo-controlled Period and Follow-up
Adverse Event
|
0
|
1
|
1
|
|
Placebo-controlled Period and Follow-up
Protocol Violation
|
0
|
2
|
1
|
|
Placebo-controlled Period and Follow-up
Withdrawal by Subject
|
0
|
1
|
2
|
|
Placebo-controlled Period and Follow-up
Lost to Follow-up
|
0
|
2
|
0
|
Baseline Characteristics
Persistence of Effect and Safety of Valbenazine for the Treatment of Tardive Dyskinesia
Baseline characteristics by cohort
| Measure |
Placebo-controlled Placebo
n=58 Participants
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Placebo-controlled Valbenazine
n=59 Participants
Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Total
n=117 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.2 Years
STANDARD_DEVIATION 8.3 • n=99 Participants
|
58.0 Years
STANDARD_DEVIATION 8.0 • n=107 Participants
|
58.6 Years
STANDARD_DEVIATION 8.1 • n=206 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=99 Participants
|
30 Participants
n=107 Participants
|
57 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=99 Participants
|
29 Participants
n=107 Participants
|
60 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
32 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
64 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=99 Participants
|
27 Participants
n=107 Participants
|
53 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
21 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
36 Participants
n=99 Participants
|
43 Participants
n=107 Participants
|
79 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Abnormal Involuntary Movement Scale at Study Baseline
|
10.3 Score on scale
STANDARD_DEVIATION 3.7 • n=99 Participants
|
11.0 Score on scale
STANDARD_DEVIATION 4.1 • n=107 Participants
|
10.7 Score on scale
STANDARD_DEVIATION 3.9 • n=206 Participants
|
PRIMARY outcome
Timeframe: Week 8, Week 16Population: Persistence of effect analysis set, which includes all randomized participants who received at least one dose of randomized study drug and have at least one AIMS assessment during the placebo-controlled period. Participants who do not have an AIMS assessment at a scheduled or mapped early termination visit are not included in the analysis.
The AIMS rates 10 items of involuntary movement, each item ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Items assess facial, oral, extremity, and trunk movements, as well as self-awareness of abnormal movements. The AIMS Dyskinesia Total Score is the sum of items 1-7 and ranges from 0 to 28, with higher scores indicating more severe dyskinesia. Least-squares mean were estimated using a mixed-effects model for repeated measures.
Outcome measures
| Measure |
Placebo-controlled Placebo
n=56 Participants
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Placebo-controlled Valbenazine
n=58 Participants
Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
|---|---|---|
|
Change From Randomization (Week 8) in Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score at Week 16
|
0.6 Score on scale
Interval -0.8 to 1.9
|
-1.6 Score on scale
Interval -3.0 to -0.3
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: Includes all participants who received at least one dose of study drug and have at least one postbaseline assessment. Missing data were imputed with last observation carried forward.
The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The health state index score is based on the results of the individual health profiles using the United States value set and ranges from -0.573 to 1.0, with higher scores indicating higher health utility.
Outcome measures
| Measure |
Placebo-controlled Placebo
n=57 Participants
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Placebo-controlled Valbenazine
n=59 Participants
Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
|---|---|---|
|
Change From Baseline in the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Health State Index Score at Week 16
|
0.09 Score on scale
Standard Error 0.03
|
0.16 Score on scale
Standard Error 0.03
|
SECONDARY outcome
Timeframe: Baseline, Week 16Population: Includes all participants who received at least one dose of study drug and have at least one postbaseline assessment. Missing data were imputed with last observation carried forward.
The EQ-5D-5L assesses general health-related quality of life. The second portion of the scale is a self-perceived health score assessed using a VAS that ranges from 0 ("the worst imaginable health") to 100 ("the best imaginable health").
Outcome measures
| Measure |
Placebo-controlled Placebo
n=57 Participants
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Placebo-controlled Valbenazine
n=59 Participants
Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
|---|---|---|
|
Change From Baseline in the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) at Week 16
|
4.5 Score on scale
Standard Error 2.5
|
6.5 Score on scale
Standard Error 2.8
|
Adverse Events
Open-label Valbenazine
Serious events: 3 serious events
Other events: 17 other events
Deaths: 1 deaths
Placebo-controlled Placebo
Serious events: 2 serious events
Other events: 11 other events
Deaths: 0 deaths
Placebo-controlled Valbenazine
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open-label Valbenazine
n=132 participants at risk
Participants received valbenazine 40 mg once daily for 1 week, then 80 mg once daily for the remainder of the 8-week open label period.
|
Placebo-controlled Placebo
n=59 participants at risk
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Placebo-controlled Valbenazine
n=59 participants at risk
Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
|---|---|---|---|
|
Infections and infestations
Cellulitis
|
0.00%
0/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
1.7%
1/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Infections and infestations
Sepsis
|
0.00%
0/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
1.7%
1/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.76%
1/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Metabolism and nutrition disorders
Dehydration
|
0.76%
1/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Nervous system disorders
Syncope
|
0.76%
1/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
1.7%
1/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.00%
0/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
1.7%
1/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
Other adverse events
| Measure |
Open-label Valbenazine
n=132 participants at risk
Participants received valbenazine 40 mg once daily for 1 week, then 80 mg once daily for the remainder of the 8-week open label period.
|
Placebo-controlled Placebo
n=59 participants at risk
Participants received placebo (matching valbenazine) once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
Placebo-controlled Valbenazine
n=59 participants at risk
Participants received valbenazine 80 mg once daily for 8 weeks. Randomization into this arm occurred after open-label treatment with valbenazine once daily for 8 weeks.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.76%
1/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
3.4%
2/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
1.7%
1/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Infections and infestations
Urinary tract infection
|
3.0%
4/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
10.2%
6/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Injury, poisoning and procedural complications
Fall
|
1.5%
2/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
3.4%
2/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Investigations
Blood creatine phosphokinase increased
|
0.76%
1/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
3.4%
2/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Investigations
Blood glucose increased
|
0.00%
0/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
3.4%
2/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Investigations
Weight increased
|
1.5%
2/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
3.4%
2/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.8%
5/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Nervous system disorders
Somnolence
|
3.0%
4/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
0.00%
0/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
|
Psychiatric disorders
Suicidal ideation
|
0.76%
1/132 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
3.4%
2/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
1.7%
1/59 • Open-label valbenazine group: from baseline up to randomization (Week 8). Placebo-controlled placebo and valbenazine groups: from randomization (Week 8) up to Week 20
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Generally, the PI has the right to publish results provided such publication does not violate confidentiality or IP provisions within the contract with the Sponsor. Prior to submission for publication or presentation of results, the PI must provide the Sponsor time for review. The Sponsor can request the PI to withhold or remove information from all publications. For a multi-center study, any publication of results by the PI shall not be made before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER