Tardive Dyskinesia
Conditions
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.
Interventions
DRUGNBI-98854
Sponsors
Neurocrine Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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; 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. |
| 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. |
| 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). |
Countries
Canada, Puerto Rico, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Valbenazine 40mg Participants received valbenazine 40mg once daily for up to 48 weeks. | 45 |
| Valbenazine 80mg Participants received valbenazine 40mg once daily for 4 weeks, then 80mg once daily for up to 44 weeks. | 107 |
| 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. | 11 |
| Total | 163 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 10 | 0 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 5 | 6 | 0 |
| Overall Study | Noncompliance | 1 | 6 | 2 |
| Overall Study | Physician Decision | 2 | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 8 | 0 |
Baseline characteristics
| Characteristic | Total | Valbenazine 80/40mg | Valbenazine 80mg | Valbenazine 40mg |
|---|---|---|---|---|
| Age at Diagnosis Age at Mood Disorder Diagnosis | 36.8 years | 28.3 years | 36.9 years | 40.6 years |
| Age at Diagnosis Age at Schizophrenia/Schizoaffective Diagnosis | 28.8 years | 26.2 years | 28.0 years | 30.9 years |
| Age at Tardive Dyskinesia Diagnosis | 48.4 years | 44.3 years | 49.2 years | 47.8 years |
| Age, Continuous | 57.4 years | 56.3 years | 57.8 years | 56.8 years |
| Baseline AIMS Dyskinesia Total Score | 14.6 score on a scale STANDARD_DEVIATION 4.8 | 12.8 score on a scale STANDARD_DEVIATION 4.6 | 15.0 score on a scale STANDARD_DEVIATION 4.5 | 14.2 score on a scale STANDARD_DEVIATION 5.5 |
| BMI at Screening | 28.53 kg/m^2 | 27.45 kg/m^2 | 28.95 kg/m^2 | 27.80 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 56 Participants | 1 Participants | 48 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 107 Participants | 10 Participants | 59 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Primary Psychiatric Diagnosis Mood disorder | 44 Participants | 5 Participants | 31 Participants | 8 Participants |
| Primary Psychiatric Diagnosis Schizophrenia/schizoaffective | 119 Participants | 6 Participants | 76 Participants | 37 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 48 Participants | 1 Participants | 31 Participants | 16 Participants |
| Race/Ethnicity, Customized Caucasian | 110 Participants | 10 Participants | 74 Participants | 26 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other: Latina | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other: Mulatto | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Screening BPRS Total Score | 27.9 score on a scale | 28.4 score on a scale | 27.3 score on a scale | 29.2 score on a scale |
| Sex: Female, Male Female | 77 Participants | 5 Participants | 48 Participants | 24 Participants |
| Sex: Female, Male Male | 86 Participants | 6 Participants | 59 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 163 | 0 / 35 | 1 / 107 | 0 / 11 |
| other Total, other adverse events | 0 / 163 | 5 / 35 | 15 / 107 | 1 / 11 |
| serious Total, serious adverse events | 0 / 163 | 3 / 35 | 17 / 107 | 1 / 11 |
Outcome results
Primary
Number of Participants Monitored for Long-Term Safety of Valbenazine
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.
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valbenazine 40mg | Number of Participants Monitored for Long-Term Safety of Valbenazine | 45 Participants |
| Valbenazine 80mg | Number of Participants Monitored for Long-Term Safety of Valbenazine | 107 Participants |
| Valbenazine 80/40mg | Number of Participants Monitored for Long-Term Safety of Valbenazine | 11 Participants |
Secondary
Clinical Global Impression - Global Improvement of Tardive Dyskinesia (CGI-TD) at 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).
Time frame: Week 48
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valbenazine 40mg | Clinical Global Impression - Global Improvement of Tardive Dyskinesia (CGI-TD) at Week 48 | 1.7 score on a scale | Standard Error 0.2 |
| Valbenazine 80mg | Clinical Global Impression - Global Improvement of Tardive Dyskinesia (CGI-TD) at Week 48 | 1.6 score on a scale | Standard Error 0.1 |
| Valbenazine 80/40mg | Clinical Global Impression - Global Improvement of Tardive Dyskinesia (CGI-TD) at Week 48 | 2.3 score on a scale | Standard Error 0.4 |
Secondary
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
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.
Time frame: Baseline and Week 48
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valbenazine 40mg | 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 |
| Valbenazine 80mg | 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 | -11.0 score on a scale | Standard Error 0.5 |
| Valbenazine 80/40mg | 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 | -7.2 score on a scale | Standard Error 2.2 |
Secondary
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; Central AIMS Video Raters
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.
Time frame: Baseline, Change from Baseline at Week 8, and Change from Baseline at Week 52
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valbenazine 40mg | 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 |
| Valbenazine 40mg | 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 |
| Valbenazine 40mg | 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 |
| Valbenazine 80mg | 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 | -3.5 score on a scale | Standard Error 0.4 |
| Valbenazine 80mg | 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 | 10.0 score on a scale | Standard Error 0.4 |
| Valbenazine 80mg | 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 | -3.3 score on a scale | Standard Error 0.5 |
| Valbenazine 80/40mg | 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 | 9.3 score on a scale | Standard Error 0.8 |
| Valbenazine 80/40mg | 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 | 0.2 score on a scale | Standard Error 1.3 |
| Valbenazine 80/40mg | 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 | -4.9 score on a scale | Standard Error 1.2 |
Secondary
Severity of Tardive Dyskinesia (TD) Symptoms Assessed by Abnormal Involuntary Movements Scale (AIMS) Dyskinesia Total Score Change From Baseline; On-Site AIMS Raters
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.
Time frame: Baseline, Change from Baseline at Week 8, and Change from Baseline at Week 52
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Valbenazine 40mg | 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 |
| Valbenazine 40mg | 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 |
| Valbenazine 40mg | 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 |
| Valbenazine 80mg | 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 | -5.4 score on a scale | Standard Error 0.5 |
| Valbenazine 80mg | 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 | 15.0 score on a scale | Standard Error 0.4 |
| Valbenazine 80mg | 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 | -4.6 score on a scale | Standard Error 0.7 |
| Valbenazine 80/40mg | 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 | 12.8 score on a scale | Standard Error 1.4 |
| Valbenazine 80/40mg | 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 | -3.3 score on a scale | Standard Error 1.8 |
| Valbenazine 80/40mg | 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 | -7.4 score on a scale | Standard Error 1.6 |