Trial Outcomes & Findings for NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder (NCT NCT01393600)

Last Updated: 2017-08-10

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

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

Day 15 and 29, averaged

Results posted on

2017-08-10

Participant Flow

This study enrolled patients with a clinical diagnosis of schizophrenia or schizoaffective disorder with moderate or severe symptoms of tardive dyskinesia (TD) from 10 centers in the United States. The last patient completed in February 2012.

Participant milestones

Participant milestones
Measure	Placebo, Then Valbenazine 12.5 mg Participants first received Placebo (matching valbenazine solution) once daily from Day 1 to 14, then they received valbenazine 12.5 mg solution once daily from Day 15 to 28.	Valbenazine 12.5 mg, Then Placebo Participants first received valbenazine 12.5 mg solution once daily from Day 1 to 14, then they received Placebo (matching valbenazine solution) once daily from Day 15 to 28.	Placebo, Then Valbenazine 50 mg Participants first received Placebo (matching valbenazine solution) once daily from Day 1 to 14, then they received valbenazine 50 mg solution once daily from Day 15 to 28.	Valbenazine 50 mg, Then Placebo Participants first received valbenazine 50 mg solution once daily from Day 1 to 14, then they received Placebo (matching valbenazine solution) once daily from Day 15 to 28.
Treatment Period 1 (Day 1 to 14) STARTED	9	8	10	10
Treatment Period 1 (Day 1 to 14) COMPLETED	9	7	9	9
Treatment Period 1 (Day 1 to 14) NOT COMPLETED	0	1	1	1
Treatment Period 2 (Day 15 to 28) STARTED	9	7	9	9
Treatment Period 2 (Day 15 to 28) COMPLETED	9	7	7	8
Treatment Period 2 (Day 15 to 28) NOT COMPLETED	0	0	2	1
Follow-up Period (Day 29 to 35) STARTED	9	7	7	8
Follow-up Period (Day 29 to 35) COMPLETED	9	7	6	8
Follow-up Period (Day 29 to 35) NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Valbenazine 12.5 mg, Then Placebo Participants first received valbenazine 12.5 mg solution once daily from Day 1 to 14, then they received Placebo (matching valbenazine solution) once daily from Day 15 to 28.	Placebo, Then Valbenazine 50 mg Participants first received Placebo (matching valbenazine solution) once daily from Day 1 to 14, then they received valbenazine 50 mg solution once daily from Day 15 to 28.	Valbenazine 50 mg, Then Placebo Participants first received valbenazine 50 mg solution once daily from Day 1 to 14, then they received Placebo (matching valbenazine solution) once daily from Day 15 to 28.
Treatment Period 1 (Day 1 to 14) Protocol Violation	1	0	0
Treatment Period 1 (Day 1 to 14) Withdrawal by Subject	0	1	0
Treatment Period 1 (Day 1 to 14) Adverse Event	0	0	1
Treatment Period 2 (Day 15 to 28) Withdrawal by Subject	0	0	1
Treatment Period 2 (Day 15 to 28) Lost to Follow-up	0	1	0
Treatment Period 2 (Day 15 to 28) Physician Decision	0	1	0
Follow-up Period (Day 29 to 35) Withdrawal by Subject	0	1	0

Baseline Characteristics

NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Subjects n=37 Participants All randomized subjects who received at least one dose of study drug.
Age, Continuous	51.1 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Race/Ethnicity, Customized Black	12 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	15 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	10 Participants n=5 Participants
Body Mass Index	29.9 kg/m^2 n=5 Participants
Age of Schizophrenia/Schizoaffective Disorder Diagnosis	25.8 years n=5 Participants
Age at TD Diagnosis	41.7 years n=5 Participants

PRIMARY outcome

Timeframe: Day 15 and 29, averaged

Population: Intent to treat (ITT) analysis set (all subjects who received at least 8 doses of study drug during Treatment Period 1 and had an AIMS dyskinesia total score value for Day 15).

Outcome measures

Outcome measures
Measure	Placebo n=33 Participants Placebo (matching valbenazine solution)	Valbenazine 12.5 mg n=17 Participants Valbenazine 12.5 mg solution	Valbenazine 50 mg n=15 Participants Valbenazine 50 mg solution	Valbenazine 50mg Participants who received valbenazine 50mg solution once daily from Day 1 to 14 and participants who received valbenazine 50mg solution from Day 15 to 28.
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score	9.9 units on a scale Standard Error 0.7	9.1 units on a scale Standard Error 1.2	8.8 units on a scale Standard Error 1.2	—

SECONDARY outcome

Timeframe: Day 15 and 29, averaged

Population: Intent to treat (ITT) analysis set (all subjects who received at least 8 doses of study drug during Treatment Period 1 and had an AIMS dyskinesia total score value for Day 15).

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=16 Participants Placebo (matching valbenazine solution)	Valbenazine 12.5 mg n=17 Participants Valbenazine 12.5 mg solution	Valbenazine 50 mg n=17 Participants Valbenazine 50 mg solution	Valbenazine 50mg n=15 Participants Participants who received valbenazine 50mg solution once daily from Day 1 to 14 and participants who received valbenazine 50mg solution from Day 15 to 28.
Clinical Global Impression - Global Improvement of TD (CGI-TD)	2.2 units on a scale Standard Error 0.2	2.2 units on a scale Standard Error 0.2	3.2 units on a scale Standard Error 0.3	2.6 units on a scale Standard Error 0.3

POST_HOC outcome

Timeframe: Day 15 and 29, averaged

Population: Intent to treat (ITT) analysis set (all subjects who received at least 8 doses of study drug during Treatment Period 1 and had an AIMS dyskinesia total score value for Day 15).

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Placebo (matching valbenazine solution)	Valbenazine 12.5 mg n=15 Participants Valbenazine 12.5 mg solution	Valbenazine 50 mg n=10 Participants Valbenazine 50 mg solution	Valbenazine 50mg Participants who received valbenazine 50mg solution once daily from Day 1 to 14 and participants who received valbenazine 50mg solution from Day 15 to 28.
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score for Combined NBI-98854 Dose Groups (Excluding 1 Site)	10.3 units on a scale Standard Error 0.9	9.9 units on a scale Standard Error 1.1	6.1 units on a scale Standard Error 1.2	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

NBI-98854 12.5 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

NBI-98854 50 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=35 participants at risk Placebo (matching NBI-98854 solution) for 28 days followed by 7 days of posttreatment.	NBI-98854 12.5 mg n=17 participants at risk NBI-98854 12.5 mg solution for 28 days followed by 7 days of posttreatment.	NBI-98854 50 mg n=19 participants at risk NBI-98854 50 mg solution for 28 days followed by 7 days of posttreatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/35 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	0.00% 0/19 • up to 35 days

Other adverse events

Other adverse events
Measure	Placebo n=35 participants at risk Placebo (matching NBI-98854 solution) for 28 days followed by 7 days of posttreatment.	NBI-98854 12.5 mg n=17 participants at risk NBI-98854 12.5 mg solution for 28 days followed by 7 days of posttreatment.	NBI-98854 50 mg n=19 participants at risk NBI-98854 50 mg solution for 28 days followed by 7 days of posttreatment.
Eye disorders Vision blurred	0.00% 0/35 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Gastrointestinal disorders Diarrhoea	5.7% 2/35 • Number of events 4 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	0.00% 0/19 • up to 35 days
Gastrointestinal disorders Vomiting	0.00% 0/35 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	0.00% 0/19 • up to 35 days
General disorders Fatigue	5.7% 2/35 • Number of events 2 • up to 35 days	0.00% 0/17 • up to 35 days	0.00% 0/19 • up to 35 days
Infections and infestations Furuncle	0.00% 0/35 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Infections and infestations Gastroenteritis viral	0.00% 0/35 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Investigations Blood creatine phosphokinase increased	0.00% 0/35 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Investigations Urine analysis abnormal	0.00% 0/35 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	0.00% 0/19 • up to 35 days
Musculoskeletal and connective tissue disorders Back pain	5.7% 2/35 • Number of events 2 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	0.00% 0/19 • up to 35 days
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/35 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	0.00% 0/19 • up to 35 days
Nervous system disorders Akathisia	0.00% 0/35 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Nervous system disorders Headache	5.7% 2/35 • Number of events 5 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	0.00% 0/19 • up to 35 days
Nervous system disorders Paraesthesia	0.00% 0/35 • up to 35 days	5.9% 1/17 • Number of events 1 • up to 35 days	0.00% 0/19 • up to 35 days
Nervous system disorders Sedation	2.9% 1/35 • Number of events 1 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Nervous system disorders Somnolence	0.00% 0/35 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Psychiatric disorders Restlessness	0.00% 0/35 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/35 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days
Skin and subcutaneous tissue disorders Pruritis	0.00% 0/35 • up to 35 days	0.00% 0/17 • up to 35 days	5.3% 1/19 • Number of events 1 • up to 35 days

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