Tardive Dyskinesia
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of two doses (12.5 and 50 mg) of NBI-98854 administered once daily (q.d.) for the treatment of tardive dyskinesia in subjects with schizophrenia or schizoaffective disorder.
Interventions
DRUGNBI-98854
12.5 mg powder in bottle once daily for 14 days
DRUGPlacebo
Solution containing no active substance
Sponsors
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a clinical diagnosis of schizophrenia or schizoaffective disorder and a clinical diagnosis of neuroleptic-induced tardive dyskinesia as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), 333.82 (see Appendix 17.1) for at least 3 months prior to screening. * Be receiving a stable dose of antipsychotic medication for a minimum of 30 days before study start. Subjects who are not using antipsychotic medication must have stable psychiatric status. * Have the doses of concurrent medications and the conditions being treated be stable for a minimum of 30 days before study start and be expected to remain stable during the study. * Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal birth control during the study. * Female subjects must not be pregnant. * Be in good general health and expected to complete the clinical study as designed. * Have a body mass index (BMI) of 18 to 38 kg/m2 (both inclusive). * Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol. * Have a negative urine drug screen (negative for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids) at screening and study start, except for any subject receiving a stable dose of benzodiazepine. * Have a negative alcohol breath test at screening and study start.
Exclusion criteria
* Have an active clinically significant unstable medical condition within 1 month (30 days) prior to screening. * Have a history of substance dependence or substance (drug) or alcohol abuse within the 3 months before study start(nicotine and caffeine dependence are not exclusionary). * Have a known history of neuroleptic malignant syndrome. * Have a significant risk of suicidal or violent behavior. * Receiving any excluded concomitant medication such as reserpine, metoclopramide, stimulants, or tetrabenazine * Receiving medication for the treatment of tardive dyskinesia. * Have a positive human immunodeficiency virus antibody, (HIV-Ab), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody result at screening or have a history of positive result. * Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study. * Have an allergy, hypersensitivity, or intolerance to tetrabenazine. * Have had previous exposure with NBI-98854.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score | Day 15 and 29, averaged | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Global Improvement of TD (CGI-TD) | Day 15 and 29, averaged | 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). |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects All randomized subjects who received at least one dose of study drug. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-up Period (Day 29 to 35) | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Treatment Period 1 (Day 1 to 14) | Adverse Event | 0 | 0 | 0 | 1 |
| Treatment Period 1 (Day 1 to 14) | Protocol Violation | 0 | 1 | 0 | 0 |
| Treatment Period 1 (Day 1 to 14) | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Treatment Period 2 (Day 15 to 28) | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Treatment Period 2 (Day 15 to 28) | Physician Decision | 0 | 0 | 1 | 0 |
| Treatment Period 2 (Day 15 to 28) | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age at TD Diagnosis | 41.7 years |
| Age, Continuous | 51.1 years |
| Age of Schizophrenia/Schizoaffective Disorder Diagnosis | 25.8 years |
| Body Mass Index | 29.9 kg/m^2 |
| Race/Ethnicity, Customized Black | 12 Participants |
| Race/Ethnicity, Customized Caucasian | 15 Participants |
| Race/Ethnicity, Customized Hispanic | 10 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 17 | 0 / 19 |
| other Total, other adverse events | 4 / 35 | 4 / 17 | 6 / 19 |
| serious Total, serious adverse events | 0 / 35 | 1 / 17 | 0 / 19 |
Outcome results
Primary
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score
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.
Time frame: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score | 9.9 units on a scale | Standard Error 0.7 |
| Valbenazine 12.5 mg | Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score | 9.1 units on a scale | Standard Error 1.2 |
| Valbenazine 50 mg | Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score | 8.8 units on a scale | Standard Error 1.2 |
p-value: 0.58895% CI: [-3.3, 1.9]ANOVA
p-value: 0.418495% CI: [-3.8, 1.6]ANOVA
Secondary
Clinical Global Impression - Global Improvement of TD (CGI-TD)
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).
Time frame: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Global Impression - Global Improvement of TD (CGI-TD) | 2.2 units on a scale | Standard Error 0.2 |
| Valbenazine 12.5 mg | Clinical Global Impression - Global Improvement of TD (CGI-TD) | 2.2 units on a scale | Standard Error 0.2 |
| Valbenazine 50 mg | Clinical Global Impression - Global Improvement of TD (CGI-TD) | 3.2 units on a scale | Standard Error 0.3 |
| Valbenazine 50mg | Clinical Global Impression - Global Improvement of TD (CGI-TD) | 2.6 units on a scale | Standard Error 0.3 |
Post Hoc
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score for Combined NBI-98854 Dose Groups (Excluding 1 Site)
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.
Time frame: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Valbenazine 12.5 mg | Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score for Combined NBI-98854 Dose Groups (Excluding 1 Site) | 9.9 units on a scale | Standard Error 1.1 |
| Valbenazine 50 mg | Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score for Combined NBI-98854 Dose Groups (Excluding 1 Site) | 6.1 units on a scale | Standard Error 1.2 |
p-value: 0.676195% CI: [-2.4, 1.6]ANOVA
p-value: 0.001595% CI: [-6.6, -1.8]ANOVA