Trial Outcomes & Findings for NBI-98854 Dose Titration Study for the Treatment of Tardive Dyskinesia (NCT NCT01733121)

Last Updated: 2017-08-10

Results Overview

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

PHASE2

Target enrollment

102 participants

Primary outcome timeframe

Baseline and Week 6

Results posted on

2017-08-10

Participant Flow

This study enrolled patients with schizophrenia or schizoaffective disorder with tardive dyskinesia (TD), a mood disorder with TD, or a GI disorder with TD from 29 centers in the United States and Puerto Rico. The last patient completed in December 2013.

Participant milestones

Participant milestones
Measure	Placebo Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.	Valbenazine Participants could receive valbenazine 25mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks); flexible dose escalation.
Double-Blind Period (Week 0 to 6) STARTED	51	51
Double-Blind Period (Week 0 to 6) COMPLETED	44	46
Double-Blind Period (Week 0 to 6) NOT COMPLETED	7	5
Follow-Up Period (Week 6 to 8) STARTED	44	46
Follow-Up Period (Week 6 to 8) COMPLETED	44	46
Follow-Up Period (Week 6 to 8) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.	Valbenazine Participants could receive valbenazine 25mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks); flexible dose escalation.
Double-Blind Period (Week 0 to 6) Adverse Event	2	0
Double-Blind Period (Week 0 to 6) Non-compliance	3	2
Double-Blind Period (Week 0 to 6) Withdrawal by Subject	1	3
Double-Blind Period (Week 0 to 6) Lost to Follow-up	1	0

Baseline Characteristics

Date of diagnosis was not available for some subjects.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=49 Participants Participants received Placebo capsule (matching valbenazine capsules) daily for 6 weeks.	Valbenazine n=51 Participants Participants received valbenazine 25mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks).	Total n=100 Participants Total of all reporting groups
Age, Continuous	55.6 years n=49 Participants	56.7 years n=51 Participants	56.2 years n=100 Participants
Sex: Female, Male Female	22 Participants n=49 Participants	21 Participants n=51 Participants	43 Participants n=100 Participants
Sex: Female, Male Male	27 Participants n=49 Participants	30 Participants n=51 Participants	57 Participants n=100 Participants
Race/Ethnicity, Customized American Indian/Alaska native	1 Participants n=49 Participants	0 Participants n=51 Participants	1 Participants n=100 Participants
Race/Ethnicity, Customized American Indian/Alaska native, Caucasian	1 Participants n=49 Participants	0 Participants n=51 Participants	1 Participants n=100 Participants
Race/Ethnicity, Customized Black/African American	16 Participants n=49 Participants	18 Participants n=51 Participants	34 Participants n=100 Participants
Race/Ethnicity, Customized Caucasian	30 Participants n=49 Participants	33 Participants n=51 Participants	63 Participants n=100 Participants
Race/Ethnicity, Customized Other/mixed	1 Participants n=49 Participants	0 Participants n=51 Participants	1 Participants n=100 Participants
Body Mass Index	28.19 kg/m^2 n=49 Participants	29.02 kg/m^2 n=51 Participants	28.62 kg/m^2 n=100 Participants
Disease Category Schizophrenia or schizoaffective disorder	30 Participants n=49 Participants	28 Participants n=51 Participants	58 Participants n=100 Participants
Disease Category Mood disorder	18 Participants n=49 Participants	20 Participants n=51 Participants	38 Participants n=100 Participants
Disease Category Gastrointestinal disorder	1 Participants n=49 Participants	3 Participants n=51 Participants	4 Participants n=100 Participants
Age at TD Diagnosis	49.5 years n=36 Participants • Date of diagnosis was not available for some subjects.	48.9 years n=39 Participants • Date of diagnosis was not available for some subjects.	49.2 years n=75 Participants • Date of diagnosis was not available for some subjects.
BPRS Total Score	30.1 units on a scale n=49 Participants	30.1 units on a scale n=51 Participants	30.1 units on a scale n=100 Participants
Baseline AIMS Total Dyskinesia Score	7.9 units on a scale STANDARD_DEVIATION 4.5 • n=44 Participants • Includes subjects with a central video raters' AIMS dyskinesia total score change from baseline value at Week 6	8.0 units on a scale STANDARD_DEVIATION 3.5 • n=45 Participants • Includes subjects with a central video raters' AIMS dyskinesia total score change from baseline value at Week 6	8.0 units on a scale STANDARD_DEVIATION 4.0 • n=89 Participants • Includes subjects with a central video raters' AIMS dyskinesia total score change from baseline value at Week 6

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Per protocol analysis set (subjects in the ITT analysis set that had an evaluable, blinded, central video raters' AIMS dyskinesia total score change from baseline value at Week 6, had a quantifiable NBI-98782 plasma concentration at Week 6 \[for subjects in the NBI-98854 group\], and had no efficacy-related important protocol deviations)

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.	Valbenazine n=32 Participants Participants first received valbenazine 25mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks).
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6	-0.3 units on a scale Standard Error 1.1	-3.4 units on a scale Standard Error 1.2

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.	Valbenazine n=32 Participants Participants first received valbenazine 25mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks).
Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 6	3.1 units on a scale Interval 2.5 to 3.6	2.2 units on a scale Interval 1.6 to 2.9

SECONDARY outcome

Timeframe: Week 6

Population: Intent to Treat (ITT) analysis set (all subjects in the safety analysis set with an evaluable, blinded, central video raters' AIMS dyskinesia total score change from baseline value at one or more scheduled assessment times during the double-blind treatment period)

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.	Valbenazine n=45 Participants Participants first received valbenazine 25mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks).
AIMS Dyskinesia Total Score Change From Baseline at Week 6	-0.2 units on a scale Interval -2.4 to 2.0	-2.6 units on a scale Interval -4.9 to -0.3

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received Placebo capsule (matching valbenazine capsules) once daily for 6 weeks.	Valbenazine n=45 Participants Participants first received valbenazine 25mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks).
Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 6	3.1 units on a scale Interval 2.5 to 3.6	2.2 units on a scale Interval 1.7 to 2.8

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 11 other events

Deaths: 1 deaths

Valbenazine

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=49 participants at risk Participants received Placebo capsule (matching valbenazine capsules) daily for 6 weeks followed by 2 weeks posttreatment period.	Valbenazine n=51 participants at risk Participants first received valbenazine 5mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks) followed by 2 weeks posttreatment period.
Renal and urinary disorders Urinary retention	2.0% 1/49 • Number of events 1 • up to 8 weeks	0.00% 0/51 • up to 8 weeks
Nervous system disorders Convulsion	2.0% 1/49 • Number of events 2 • up to 8 weeks	0.00% 0/51 • up to 8 weeks
Cardiac disorders Myocardial infarction	2.0% 1/49 • Number of events 1 • up to 8 weeks	0.00% 0/51 • up to 8 weeks

Other adverse events

Other adverse events
Measure	Placebo n=49 participants at risk Participants received Placebo capsule (matching valbenazine capsules) daily for 6 weeks followed by 2 weeks posttreatment period.	Valbenazine n=51 participants at risk Participants first received valbenazine 5mg once daily for 2 weeks, then 50mg once daily for 2 weeks, then 75mg once daily for 2 weeks (a total of 6 weeks) followed by 2 weeks posttreatment period.
Gastrointestinal disorders Constipation	6.1% 3/49 • Number of events 3 • up to 8 weeks	3.9% 2/51 • Number of events 2 • up to 8 weeks
Gastrointestinal disorders Dry mouth	0.00% 0/49 • up to 8 weeks	5.9% 3/51 • Number of events 3 • up to 8 weeks
Gastrointestinal disorders Nausea	4.1% 2/49 • Number of events 2 • up to 8 weeks	5.9% 3/51 • Number of events 3 • up to 8 weeks
Gastrointestinal disorders Vomiting	0.00% 0/49 • up to 8 weeks	5.9% 3/51 • Number of events 3 • up to 8 weeks
General disorders Fatigue	4.1% 2/49 • Number of events 2 • up to 8 weeks	9.8% 5/51 • Number of events 5 • up to 8 weeks
Infections and infestations Urinary tract infection	6.1% 3/49 • Number of events 3 • up to 8 weeks	3.9% 2/51 • Number of events 2 • up to 8 weeks
Metabolism and nutrition disorders Decreased appetite	0.00% 0/49 • up to 8 weeks	7.8% 4/51 • Number of events 4 • up to 8 weeks
Nervous system disorders Headache	4.1% 2/49 • Number of events 2 • up to 8 weeks	9.8% 5/51 • Number of events 5 • up to 8 weeks
Nervous system disorders Somnolence	2.0% 1/49 • Number of events 1 • up to 8 weeks	5.9% 3/51 • Number of events 3 • up to 8 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