Trial Outcomes & Findings for Safety and Tolerability Study of NBI-98854 for the Treatment of Tardive Dyskinesia (NCT NCT02405091)

Last Updated: 2018-11-30

Results Overview

Number of participants monitored for long-term safety through reporting of treatment-emergent adverse events and monitoring of vital signs, clinical laboratory values, and ECG. Summaries of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

167 participants

Primary outcome timeframe

52 weeks

Results posted on

2018-11-30

Participant Flow

This study enrolled participants with clinical diagnoses of schizophrenia or schizoaffective disorder or mood disorder with neuroleptic-induced tardive dyskinesia (TD) from 45 centers in North America and Puerto Rico.

Participant milestones

Participant milestones
Measure	Valbenazine 40mg Participants received valbenazine 40mg capsule once daily for up to 48 weeks.	Valbenazine 80mg Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks.	Valbenazine 80/40mg Participants received valbenazine 40mg once daily for 4 weeks, then 80 mg. Participants who were unable to tolerate the 80 mg dose had a dose decrease to 40 mg capsule once daily for up to 44 weeks.
Overall Study STARTED	49	107	11
Overall Study COMPLETED	20	74	9
Overall Study NOT COMPLETED	29	33	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Valbenazine 40mg Participants received valbenazine 40mg capsule once daily for up to 48 weeks.	Valbenazine 80mg Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks.	Valbenazine 80/40mg Participants received valbenazine 40mg once daily for 4 weeks, then 80 mg. Participants who were unable to tolerate the 80 mg dose had a dose decrease to 40 mg capsule once daily for up to 44 weeks.
Overall Study Adverse Event	16	10	0
Overall Study Protocol Violation	1	0	0
Overall Study Noncompliance	1	6	2
Overall Study Withdrawal by Subject	4	8	0
Overall Study Death	0	1	0
Overall Study Lost to Follow-up	5	6	0
Overall Study Physician Decision	2	2	0

Baseline Characteristics

Date of diagnosis was not available for some participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Valbenazine 40mg n=45 Participants Participants received valbenazine 40mg once daily for up to 48 weeks.	Valbenazine 80mg n=107 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks.	Valbenazine 80/40mg n=11 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80 mg. Participants who were unable to tolerate the 80 mg dose had a dose decrease to 40 mg capsule once daily for up to 44 weeks.	Total n=163 Participants Total of all reporting groups
Age, Continuous	56.8 years n=45 Participants	57.8 years n=107 Participants	56.3 years n=11 Participants	57.4 years n=163 Participants
Sex: Female, Male Female	24 Participants n=45 Participants	48 Participants n=107 Participants	5 Participants n=11 Participants	77 Participants n=163 Participants
Sex: Female, Male Male	21 Participants n=45 Participants	59 Participants n=107 Participants	6 Participants n=11 Participants	86 Participants n=163 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=45 Participants	48 Participants n=107 Participants	1 Participants n=11 Participants	56 Participants n=163 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=45 Participants	59 Participants n=107 Participants	10 Participants n=11 Participants	107 Participants n=163 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=45 Participants	0 Participants n=107 Participants	0 Participants n=11 Participants	0 Participants n=163 Participants
Race/Ethnicity, Customized Asian	1 Participants n=45 Participants	0 Participants n=107 Participants	0 Participants n=11 Participants	1 Participants n=163 Participants
Race/Ethnicity, Customized Black or African American	16 Participants n=45 Participants	31 Participants n=107 Participants	1 Participants n=11 Participants	48 Participants n=163 Participants
Race/Ethnicity, Customized Caucasian	26 Participants n=45 Participants	74 Participants n=107 Participants	10 Participants n=11 Participants	110 Participants n=163 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=45 Participants	1 Participants n=107 Participants	0 Participants n=11 Participants	2 Participants n=163 Participants
Race/Ethnicity, Customized Other: Latina	1 Participants n=45 Participants	0 Participants n=107 Participants	0 Participants n=11 Participants	1 Participants n=163 Participants
Race/Ethnicity, Customized Other: Mulatto	0 Participants n=45 Participants	1 Participants n=107 Participants	0 Participants n=11 Participants	1 Participants n=163 Participants
BMI at Screening	27.80 kg/m^2 n=45 Participants	28.95 kg/m^2 n=107 Participants	27.45 kg/m^2 n=11 Participants	28.53 kg/m^2 n=163 Participants
Primary Psychiatric Diagnosis Schizophrenia/schizoaffective	37 Participants n=45 Participants	76 Participants n=107 Participants	6 Participants n=11 Participants	119 Participants n=163 Participants
Primary Psychiatric Diagnosis Mood disorder	8 Participants n=45 Participants	31 Participants n=107 Participants	5 Participants n=11 Participants	44 Participants n=163 Participants
Age at Diagnosis Age at Schizophrenia/Schizoaffective Diagnosis	30.9 years n=32 Participants • Date of diagnosis was not available for some participants.	28.0 years n=69 Participants • Date of diagnosis was not available for some participants.	26.2 years n=5 Participants • Date of diagnosis was not available for some participants.	28.8 years n=106 Participants • Date of diagnosis was not available for some participants.
Age at Diagnosis Age at Mood Disorder Diagnosis	40.6 years n=8 Participants • Date of diagnosis was not available for some participants.	36.9 years n=30 Participants • Date of diagnosis was not available for some participants.	28.3 years n=4 Participants • Date of diagnosis was not available for some participants.	36.8 years n=42 Participants • Date of diagnosis was not available for some participants.
Age at Tardive Dyskinesia Diagnosis	47.8 years n=38 Participants • Date of diagnosis was not available for some participants.	49.2 years n=81 Participants • Date of diagnosis was not available for some participants.	44.3 years n=10 Participants • Date of diagnosis was not available for some participants.	48.4 years n=129 Participants • Date of diagnosis was not available for some participants.
Screening BPRS Total Score	29.2 score on a scale n=45 Participants	27.3 score on a scale n=107 Participants	28.4 score on a scale n=11 Participants	27.9 score on a scale n=163 Participants
Baseline AIMS Dyskinesia Total Score	14.2 score on a scale STANDARD_DEVIATION 5.5 • n=45 Participants	15.0 score on a scale STANDARD_DEVIATION 4.5 • n=107 Participants	12.8 score on a scale STANDARD_DEVIATION 4.6 • n=11 Participants	14.6 score on a scale STANDARD_DEVIATION 4.8 • n=163 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: Safety analysis set: includes all participants who were enrolled in the study and received study drug, with the following two exclusions: (a) participants who withdrew from the study and returned all previously dispensed study drug with all doses present, and (b) participants who had no post-baseline data collected

Outcome measures

Outcome measures
Measure	Valbenazine 40mg n=45 Participants Participants received valbenazine 40mg once daily for up to 48 weeks.	Valbenazine 80mg n=107 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks.	Valbenazine 80/40mg n=11 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg. Participants who were unable to tolerate the 80mg dose had a dose decrease to 40mg capsule once daily for up to 44 weeks.
Number of Participants Monitored for Long-Term Safety of Valbenazine	45 Participants	107 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline and Week 48

Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by On-Site 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

Outcome measures
Measure	Valbenazine 40mg n=20 Participants Participants received valbenazine 40mg once daily for up to 48 weeks.	Valbenazine 80mg n=74 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks.	Valbenazine 80/40mg n=9 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg. Participants who were unable to tolerate the 80mg dose had a dose decrease to 40mg capsule once daily for up to 44 weeks.
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 48; On-site AIMS Raters	-10.2 score on a scale Standard Error 1.2	-11.0 score on a scale Standard Error 0.5	-7.2 score on a scale Standard Error 2.2

SECONDARY outcome

Timeframe: Baseline, Change from Baseline at Week 8, and Change from Baseline at Week 52

Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by the 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

Outcome measures
Measure	Valbenazine 40mg n=45 Participants Participants received valbenazine 40mg once daily for up to 48 weeks.	Valbenazine 80mg n=107 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks.	Valbenazine 80/40mg n=11 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg. Participants who were unable to tolerate the 80mg dose had a dose decrease to 40mg capsule once daily for up to 44 weeks.
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; Central AIMS Video Raters At Baseline	10.2 score on a scale Standard Error 0.6	10.0 score on a scale Standard Error 0.4	9.3 score on a scale Standard Error 0.8
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; Central AIMS Video Raters Change from Baseline at Week 8	-4.5 score on a scale Standard Error 0.7	-3.5 score on a scale Standard Error 0.4	-4.9 score on a scale Standard Error 1.2
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; Central AIMS Video Raters Change from Baseline at Week 52	-1.8 score on a scale Standard Error 1.0	-3.3 score on a scale Standard Error 0.5	0.2 score on a scale Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline, Change from Baseline at Week 8, and Change from Baseline at Week 52

Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by On-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.

Outcome measures

Outcome measures
Measure	Valbenazine 40mg n=45 Participants Participants received valbenazine 40mg once daily for up to 48 weeks.	Valbenazine 80mg n=107 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks.	Valbenazine 80/40mg n=11 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg. Participants who were unable to tolerate the 80mg dose had a dose decrease to 40mg capsule once daily for up to 44 weeks.
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; On-Site AIMS Raters At Baseline	14.2 score on a scale Standard Error 0.8	15.0 score on a scale Standard Error 0.4	12.8 score on a scale Standard Error 1.4
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; On-Site AIMS Raters Change from Baseline at Week 8	-7.1 score on a scale Standard Error 1.0	-5.4 score on a scale Standard Error 0.5	-7.4 score on a scale Standard Error 1.6
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; On-Site AIMS Raters Change from Baseline at Week 52	-3.8 score on a scale Standard Error 1.2	-4.6 score on a scale Standard Error 0.7	-3.3 score on a scale Standard Error 1.8

SECONDARY outcome

Timeframe: Week 48

Clinician's perspective of the participant's overall improvement of TD symptoms since initiation of study drug dosing. 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	Valbenazine 40mg n=20 Participants Participants received valbenazine 40mg once daily for up to 48 weeks.	Valbenazine 80mg n=74 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks.	Valbenazine 80/40mg n=9 Participants Participants received valbenazine 40mg once daily for 4 weeks, then 80mg. Participants who were unable to tolerate the 80mg dose had a dose decrease to 40mg capsule once daily for up to 44 weeks.
Clinical Global Impression - Global Improvement of Tardive Dyskinesia (CGI-TD) at Week 48	1.7 score on a scale Standard Error 0.2	1.6 score on a scale Standard Error 0.1	2.3 score on a scale Standard Error 0.4

Adverse Events

Valbenazine 40 mg Through Week 4

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Valbenazine 40mg Week 4 Through Week 52

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Valbenazine 80mg Week 4 Through Week 52

Serious events: 17 serious events

Other events: 15 other events

Deaths: 1 deaths

Valbenazine 80/40mg Week 4 Through Week 52

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Valbenazine 40 mg Through Week 4 n=163 participants at risk Participants received valbenazine 40mg capsule once daily for 4 weeks.	Valbenazine 40mg Week 4 Through Week 52 n=35 participants at risk Participants received valbenazine 40mg capsule once daily for up to 44 weeks from Week 4 through Week 48.	Valbenazine 80mg Week 4 Through Week 52 n=107 participants at risk Participants received valbenazine 80mg once daily for up to 44 weeks from Week 4 through Week 48.	Valbenazine 80/40mg Week 4 Through Week 52 n=11 participants at risk Participants who were unable to tolerate the 80mg dose had a dose decrease to 40mg capsule once daily for up to 44 weeks from Week 4 through Week 48.
Infections and infestations Urinary tract infection	0.00% 0/163 • Up to 52 weeks Adverse events were evaluated at regular study visits throughout the study. Events with an onset date during the first four weeks of the NBI-98854 treatment period will be summarized separately from events that occur after the Week 4 visit, as all subjects receive the same dose of 40 mg during the first 4 weeks of treatment. Events with an onset date during the NBI-98854 treatment period after Week 4 will be summarized by treatment group.	8.6% 3/35 • Up to 52 weeks Adverse events were evaluated at regular study visits throughout the study. Events with an onset date during the first four weeks of the NBI-98854 treatment period will be summarized separately from events that occur after the Week 4 visit, as all subjects receive the same dose of 40 mg during the first 4 weeks of treatment. Events with an onset date during the NBI-98854 treatment period after Week 4 will be summarized by treatment group.	8.4% 9/107 • Up to 52 weeks Adverse events were evaluated at regular study visits throughout the study. Events with an onset date during the first four weeks of the NBI-98854 treatment period will be summarized separately from events that occur after the Week 4 visit, as all subjects receive the same dose of 40 mg during the first 4 weeks of treatment. Events with an onset date during the NBI-98854 treatment period after Week 4 will be summarized by treatment group.	9.1% 1/11 • Up to 52 weeks Adverse events were evaluated at regular study visits throughout the study. Events with an onset date during the first four weeks of the NBI-98854 treatment period will be summarized separately from events that occur after the Week 4 visit, as all subjects receive the same dose of 40 mg during the first 4 weeks of treatment. Events with an onset date during the NBI-98854 treatment period after Week 4 will be summarized by treatment group.
Nervous system disorders Headache	0.00% 0/163 • Up to 52 weeks Adverse events were evaluated at regular study visits throughout the study. Events with an onset date during the first four weeks of the NBI-98854 treatment period will be summarized separately from events that occur after the Week 4 visit, as all subjects receive the same dose of 40 mg during the first 4 weeks of treatment. Events with an onset date during the NBI-98854 treatment period after Week 4 will be summarized by treatment group.	5.7% 2/35 • Up to 52 weeks Adverse events were evaluated at regular study visits throughout the study. Events with an onset date during the first four weeks of the NBI-98854 treatment period will be summarized separately from events that occur after the Week 4 visit, as all subjects receive the same dose of 40 mg during the first 4 weeks of treatment. Events with an onset date during the NBI-98854 treatment period after Week 4 will be summarized by treatment group.	5.6% 6/107 • Up to 52 weeks Adverse events were evaluated at regular study visits throughout the study. Events with an onset date during the first four weeks of the NBI-98854 treatment period will be summarized separately from events that occur after the Week 4 visit, as all subjects receive the same dose of 40 mg during the first 4 weeks of treatment. Events with an onset date during the NBI-98854 treatment period after Week 4 will be summarized by treatment group.	0.00% 0/11 • Up to 52 weeks Adverse events were evaluated at regular study visits throughout the study. Events with an onset date during the first four weeks of the NBI-98854 treatment period will be summarized separately from events that occur after the Week 4 visit, as all subjects receive the same dose of 40 mg during the first 4 weeks of treatment. Events with an onset date during the NBI-98854 treatment period after Week 4 will be summarized by treatment group.

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