Trial Outcomes & Findings for A Phase 3 Study of NBI-98854 for the Treatment of Tardive Dyskinesia (NCT NCT02274558)
NCT ID: NCT02274558
Last Updated: 2017-07-11
Results Overview
Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by blinded central AIMS video 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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
234 participants
Primary outcome timeframe
Baseline and Week 6
Results posted on
2017-07-11
Participant Flow
This study enrolled patients with schizophrenia or schizoaffective disorder with tardive dyskinesia (TD) or mood disorder with TD from 63 centers in North America and Puerto Rico. The last patient completed in August 2016.
Participant milestones
| Measure |
Placebo-Controlled Placebo
Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.
|
Placebo-Controlled Valbenazine 40mg
Participants received valbenazine 40mg capsule once daily for 6 weeks.
|
Placebo-Controlled Valbenazine 80mg
Participants received valbenazine 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
78
|
76
|
80
|
|
Overall Study
Included in the Safety Analysis Set
|
76
|
72
|
79
|
|
Overall Study
COMPLETED
|
71
|
63
|
71
|
|
Overall Study
NOT COMPLETED
|
7
|
13
|
9
|
Reasons for withdrawal
| Measure |
Placebo-Controlled Placebo
Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.
|
Placebo-Controlled Valbenazine 40mg
Participants received valbenazine 40mg capsule once daily for 6 weeks.
|
Placebo-Controlled Valbenazine 80mg
Participants received valbenazine 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
4
|
2
|
|
Overall Study
Non-compliance
|
2
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
5
|
4
|
|
Overall Study
Death
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
1
|
|
Overall Study
Physician Decision
|
0
|
2
|
1
|
Baseline Characteristics
Date of diagnosis was not available for some subjects.
Baseline characteristics by cohort
| Measure |
Placebo-Controlled Placebo
n=76 Participants
Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.
|
Placebo-Controlled Valbenazine 40mg
n=72 Participants
Participants received valbenazine 40mg capsule once daily for 6 weeks.
|
Placebo-Controlled Valbenazine 80mg
n=79 Participants
Participants received valbenazine 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks.
|
Total
n=227 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57.0 years
n=76 Participants
|
55.3 years
n=72 Participants
|
56.0 years
n=79 Participants
|
56.1 years
n=227 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=76 Participants
|
30 Participants
n=72 Participants
|
40 Participants
n=79 Participants
|
104 Participants
n=227 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=76 Participants
|
42 Participants
n=72 Participants
|
39 Participants
n=79 Participants
|
123 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=76 Participants
|
1 Participants
n=72 Participants
|
1 Participants
n=79 Participants
|
2 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native, Caucasian
|
0 Participants
n=76 Participants
|
1 Participants
n=72 Participants
|
1 Participants
n=79 Participants
|
2 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=76 Participants
|
1 Participants
n=72 Participants
|
0 Participants
n=79 Participants
|
1 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
29 Participants
n=76 Participants
|
26 Participants
n=72 Participants
|
32 Participants
n=79 Participants
|
87 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
43 Participants
n=76 Participants
|
41 Participants
n=72 Participants
|
44 Participants
n=79 Participants
|
128 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=76 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=79 Participants
|
1 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
Other: Arabic
|
1 Participants
n=76 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=79 Participants
|
1 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
Other: Hispanic
|
0 Participants
n=76 Participants
|
0 Participants
n=72 Participants
|
1 Participants
n=79 Participants
|
1 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
Other: Mexican
|
1 Participants
n=76 Participants
|
1 Participants
n=72 Participants
|
0 Participants
n=79 Participants
|
2 Participants
n=227 Participants
|
|
Race/Ethnicity, Customized
Other: Mixed
|
1 Participants
n=76 Participants
|
1 Participants
n=72 Participants
|
0 Participants
n=79 Participants
|
2 Participants
n=227 Participants
|
|
Body Mass Index
|
28.03 kg/m^2
n=76 Participants
|
28.64 kg/m^2
n=72 Participants
|
27.78 kg/m^2
n=79 Participants
|
28.13 kg/m^2
n=227 Participants
|
|
Psychiatric Diagnosis Category
Schizophrenia/Schizoaffective disorder
|
50 Participants
n=76 Participants
|
48 Participants
n=72 Participants
|
52 Participants
n=79 Participants
|
150 Participants
n=227 Participants
|
|
Psychiatric Diagnosis Category
Mood disorder
|
26 Participants
n=76 Participants
|
24 Participants
n=72 Participants
|
27 Participants
n=79 Participants
|
77 Participants
n=227 Participants
|
|
Age at TD Diagnosis
|
49.4 years
n=54 Participants • Date of diagnosis was not available for some subjects.
|
47.8 years
n=50 Participants • Date of diagnosis was not available for some subjects.
|
47.6 years
n=58 Participants • Date of diagnosis was not available for some subjects.
|
48.2 years
n=162 Participants • Date of diagnosis was not available for some subjects.
|
|
BPRS Total Score
|
29.3 units on a scale
n=76 Participants
|
30.6 units on a scale
n=72 Participants
|
29.1 units on a scale
n=79 Participants
|
29.7 units on a scale
n=227 Participants
|
|
Baseline AIMS Total Dyskinesia Score
|
9.9 units on a scale
STANDARD_DEVIATION 4.3 • n=76 Participants
|
9.7 units on a scale
STANDARD_DEVIATION 4.1 • n=72 Participants
|
10.4 units on a scale
STANDARD_DEVIATION 3.6 • n=79 Participants
|
10.0 units on a scale
STANDARD_DEVIATION 4.0 • n=227 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 6Population: Intent to treat (ITT) analysis set (all subjects in the safety analysis set who have a baseline (Day -1) AIMS dyskinesia total score value and at least one post-randomization AIMS dyskinesia total score value reported during the placebo-controlled treatment period).
Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by blinded central AIMS video 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.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.
|
Valbenazine 80mg
n=70 Participants
Participants received valbenazine 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks.
|
Valbenazine 40mg
n=63 Participants
Participants received valbenazine 40mg capsule once daily for 6 weeks.
|
|---|---|---|---|
|
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
|
-0.1 scores on a scale
Standard Error 0.4
|
-3.2 scores on a scale
Standard Error 0.4
|
-1.9 scores on a scale
Standard Error 0.4
|
SECONDARY outcome
Timeframe: Week 6Population: Intent to treat (ITT) analysis set (all subjects in the safety analysis set who have a baseline (Day -1) AIMS dyskinesia total score value and at least one post-randomization AIMS dyskinesia total score value reported during the placebo-controlled treatment period).
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).
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.
|
Valbenazine 80mg
n=63 Participants
Participants received valbenazine 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks.
|
Valbenazine 40mg
n=70 Participants
Participants received valbenazine 40mg capsule once daily for 6 weeks.
|
|---|---|---|---|
|
Clinical Global Impression of Change - TD (CGI-TD) at Week 6
|
3.2 scores on a scale
Standard Error 0.1
|
2.9 scores on a scale
Standard Error 0.1
|
2.9 scores on a scale
Standard Error 0.1
|
SECONDARY outcome
Timeframe: Week 6Population: Intent to treat (ITT) analysis set (all subjects in the safety analysis set who have a baseline (Day -1) AIMS dyskinesia total score value and at least one post-randomization AIMS dyskinesia total score value reported during the placebo-controlled treatment period).
Percentage of AIMS responders (subjects who had at least a 50 percent reduction in AIMS score from baseline)
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.
|
Valbenazine 80mg
n=63 Participants
Participants received valbenazine 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks.
|
Valbenazine 40mg
n=70 Participants
Participants received valbenazine 40mg capsule once daily for 6 weeks.
|
|---|---|---|---|
|
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Responder Analysis at Week 6
|
6 Participants
|
15 Participants
|
28 Participants
|
Adverse Events
Placebo
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Valbenazine 40mg
Serious events: 4 serious events
Other events: 9 other events
Deaths: 0 deaths
Valbenazine 80mg
Serious events: 6 serious events
Other events: 5 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Placebo
n=76 participants at risk
Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.
|
Valbenazine 40mg
n=72 participants at risk
Participants received valbenazine 40mg capsule once daily for 6 weeks.
|
Valbenazine 80mg
n=79 participants at risk
Participants received valbenazine 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks.
|
|---|---|---|---|
|
General disorders
Sudden Death
|
0.00%
0/76 • up to 6 weeks
|
0.00%
0/72 • up to 6 weeks
|
1.3%
1/79 • Number of events 1 • up to 6 weeks
|
|
Hepatobiliary disorders
Hepatitis acute
|
0.00%
0/76 • up to 6 weeks
|
0.00%
0/72 • up to 6 weeks
|
1.3%
1/79 • Number of events 1 • up to 6 weeks
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/76 • up to 6 weeks
|
1.4%
1/72 • Number of events 1 • up to 6 weeks
|
0.00%
0/79 • up to 6 weeks
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/76 • up to 6 weeks
|
1.4%
1/72 • Number of events 1 • up to 6 weeks
|
0.00%
0/79 • up to 6 weeks
|
|
Psychiatric disorders
Bipolar I disorder
|
0.00%
0/76 • up to 6 weeks
|
1.4%
1/72 • Number of events 1 • up to 6 weeks
|
0.00%
0/79 • up to 6 weeks
|
|
Psychiatric disorders
Depression
|
0.00%
0/76 • up to 6 weeks
|
0.00%
0/72 • up to 6 weeks
|
1.3%
1/79 • Number of events 1 • up to 6 weeks
|
|
Psychiatric disorders
Hostility
|
0.00%
0/76 • up to 6 weeks
|
1.4%
1/72 • Number of events 1 • up to 6 weeks
|
0.00%
0/79 • up to 6 weeks
|
|
Psychiatric disorders
Mental status changes
|
1.3%
1/76 • Number of events 1 • up to 6 weeks
|
1.4%
1/72 • Number of events 1 • up to 6 weeks
|
0.00%
0/79 • up to 6 weeks
|
|
Psychiatric disorders
Schizoaffective disorder
|
1.3%
1/76 • Number of events 1 • up to 6 weeks
|
0.00%
0/72 • up to 6 weeks
|
1.3%
1/79 • Number of events 1 • up to 6 weeks
|
|
Psychiatric disorders
Schizophrenia
|
1.3%
1/76 • Number of events 1 • up to 6 weeks
|
1.4%
1/72 • Number of events 1 • up to 6 weeks
|
0.00%
0/79 • up to 6 weeks
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/76 • up to 6 weeks
|
0.00%
0/72 • up to 6 weeks
|
1.3%
1/79 • Number of events 1 • up to 6 weeks
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/76 • up to 6 weeks
|
0.00%
0/72 • up to 6 weeks
|
1.3%
1/79 • Number of events 1 • up to 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/76 • up to 6 weeks
|
1.4%
1/72 • Number of events 1 • up to 6 weeks
|
0.00%
0/79 • up to 6 weeks
|
Other adverse events
| Measure |
Placebo
n=76 participants at risk
Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.
|
Valbenazine 40mg
n=72 participants at risk
Participants received valbenazine 40mg capsule once daily for 6 weeks.
|
Valbenazine 80mg
n=79 participants at risk
Participants received valbenazine 40mg capsule once daily for 1 week, then 80mg capsule once daily for 5 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Dry mouth
|
1.3%
1/76 • Number of events 1 • up to 6 weeks
|
6.9%
5/72 • Number of events 5 • up to 6 weeks
|
0.00%
0/79 • up to 6 weeks
|
|
Nervous system disorders
Somnolence
|
3.9%
3/76 • Number of events 3 • up to 6 weeks
|
5.6%
4/72 • Number of events 4 • up to 6 weeks
|
5.1%
4/79 • Number of events 4 • up to 6 weeks
|
|
Psychiatric disorders
Suicidal ideation
|
5.3%
4/76 • Number of events 4 • up to 6 weeks
|
4.2%
3/72 • Number of events 3 • up to 6 weeks
|
1.3%
1/79 • Number of events 1 • up to 6 weeks
|
Additional Information
Neurocrine Medical Information
Neurocrine Biosciences, Inc.
Phone: 877-641-3461
Email: [email protected]
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