Safety and Tolerability Study of NBI-98854 for the Treatment of Tardive Dyskinesia

Phase 3

Completed

• Conditions: Tardive Dyskinesia
• Interventions: Drug: NBI-98854

• Registration Number: NCT02405091
• Lead Sponsor: Neurocrine Biosciences

Brief Summary

Phase 3, open-label, study to evaluate the safety and tolerability of NBI-98854 administered once daily (qd) for a total of 48 weeks of treatment. This study will enroll approximately 150 medically stable male and female subjects with clinical diagnoses of schizophrenia or schizoaffective disorder with neuroleptic-induced TD or mood disorder with neuroleptic-induced TD.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-03-27
• Study First Submitted QC: 2015-03-27
• Study First Posted: 2015-04-01
• Primary Completion: 2017-03
• Study Completion: 2017-03
• Results First Submitted: 2018-09-11
• Status Verified: 2018-11
• Results First Submitted QC: 2018-11-29
• Last Update Submitted: 2018-11-29
• Results First Posted: 2018-11-30
• Last Update Posted: 2018-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 167

Inclusion Criteria

1. Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study.
2. Female subjects must not be pregnant.
3. Have one of the following clinical diagnoses for at least 3 months prior to screening: Schizophrenia or Schizoaffective Disorder, or Mood Disorder
4. Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months prior to screening.
5. Have moderate or severe TD
6. If using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder, be on stable doses.
7. Be in general good health.
8. Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
9. Have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids.

Exclusion Criteria

1. Have an active, clinically significant unstable medical condition within 1 month prior to screening.
2. Have a known history of substance dependence, substance (drug) or alcohol abuse.
3. Have a significant risk of suicidal or violent behavior.
4. Have a known history of neuroleptic malignant syndrome.
5. Have a known history of long QT syndrome or cardiac tachy-arrhythmia.
6. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed).
7. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study.
8. Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline.
9. Have an allergy, hypersensitivity, or intolerance to tetrabenazine.
10. Are currently pregnant or breastfeeding.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose Group 1	NBI-98854	Fixed dose of NBI-98854 administered once daily for 48 weeks
Dose Group 2	NBI-98854	Fixed dose of NBI-98854 administered once daily up to 48 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants Monitored for Long-Term Safety of Valbenazine	52 weeks	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.

Secondary Outcome Measures

Name	Time	Method
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	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.
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; On-Site AIMS Raters	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.
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; Central AIMS Video Raters	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.
Clinical Global Impression - Global Improvement of Tardive Dyskinesia (CGI-TD) at Week 48	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).