NBI-98854 Dose Titration Study for the Treatment of Tardive Dyskinesia
Primary Purpose
Tardive Dyskinesia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NBI-98854
NBI-98854
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tardive Dyskinesia
Eligibility Criteria
Inclusion Criteria:
- Have one of the following clinical diagnoses for at least 3 months prior to screening a) schizophrenia or schizoaffective disorder; b) mood disorder; or c) gastrointestinal disorder (e.g., gastroparesis, gastroesophageal reflux disease)
- Have a clinical diagnosis of neuroleptic-induced tardive dyskinesia 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 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
NBI-98854
Placebo
Arm Description
Dose titration to determine a subject's optimal dose in the range of 25 to 75 mg NBI-98854. Dose titration is performed in increments of 25 mg. NBI-98854 administered as one (1) 25 mg capsule, two (2) 25 mg capsules, or one (1) 25 mg capsule and one (1) 50 mg capsule by mouth, taken every morning between 7:00am - 10:00am for 6 weeks.
Capsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules.
Outcomes
Primary Outcome Measures
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
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 Outcome Measures
Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 6
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).
AIMS Dyskinesia Total Score Change From Baseline at Week 6
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.
Full Information
NCT ID
NCT01733121
First Posted
November 20, 2012
Last Updated
July 11, 2017
Sponsor
Neurocrine Biosciences
1. Study Identification
Unique Protocol Identification Number
NCT01733121
Brief Title
NBI-98854 Dose Titration Study for the Treatment of Tardive Dyskinesia
Official Title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Titration Study to Assess the Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Tardive Dyskinesia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neurocrine Biosciences
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of NBI-98854 (titrated to a subject's optimal dose in the range of 25 to 75 mg) administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.
Detailed Description
This is a Phase 2, randomized, double-blind, placebo-controlled, dose-titration study to evaluate the efficacy, safety, and tolerability of NBI-98854 (titrated to subject's optimal dose in the range of 25 to 75 mg) compared to placebo, administered once daily (q.d.) for a total of 6 weeks of treatment. Approximately 90 medically stable male and female subjects with one of the following clinical diagnoses will be enrolled: schizophrenia or schizoaffective disorder with neuroleptic-induced TD; mood disorder with neuroleptic-induced TD; or gastrointestinal disorder with metoclopramide-induced TD.
For subjects randomized to active treatment, the starting dose will be 25 mg NBI 98854, which may be escalated in increments of 25 mg every 2 weeks to a maximum of 75 mg to achieve an optimal dose of NBI-98854 for each subject
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tardive Dyskinesia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NBI-98854
Arm Type
Experimental
Arm Description
Dose titration to determine a subject's optimal dose in the range of 25 to 75 mg NBI-98854. Dose titration is performed in increments of 25 mg. NBI-98854 administered as one (1) 25 mg capsule, two (2) 25 mg capsules, or one (1) 25 mg capsule and one (1) 50 mg capsule by mouth, taken every morning between 7:00am - 10:00am for 6 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Capsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules.
Intervention Type
Drug
Intervention Name(s)
NBI-98854
Intervention Description
25 mg capsule
Intervention Type
Drug
Intervention Name(s)
NBI-98854
Intervention Description
50 mg capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
Description
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 6
Secondary Outcome Measure Information:
Title
Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 6
Description
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
Week 6
Title
AIMS Dyskinesia Total Score Change From Baseline at Week 6
Description
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
Week 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have one of the following clinical diagnoses for at least 3 months prior to screening a) schizophrenia or schizoaffective disorder; b) mood disorder; or c) gastrointestinal disorder (e.g., gastroparesis, gastroesophageal reflux disease)
Have a clinical diagnosis of neuroleptic-induced tardive dyskinesia 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chris O'Brien, MD
Organizational Affiliation
Neurocrine Biosciences
Official's Role
Study Director
Facility Information:
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
City
Oceanside
State/Province
California
ZIP/Postal Code
92056
Country
United States
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60640
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
City
Beachwood
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
City
Conshohocken
State/Province
Pennsylvania
ZIP/Postal Code
19428
Country
United States
City
Phoenixville
State/Province
Pennsylvania
ZIP/Postal Code
19460
Country
United States
City
Bedford
State/Province
Texas
ZIP/Postal Code
76021
Country
United States
City
DeSoto
State/Province
Texas
ZIP/Postal Code
75115
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77008
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Irving
State/Province
Texas
ZIP/Postal Code
75062
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
City
Richland
State/Province
Washington
ZIP/Postal Code
99352
Country
United States
City
Caguas
ZIP/Postal Code
00725
Country
Puerto Rico
12. IPD Sharing Statement
Citations:
PubMed Identifier
31617235
Citation
Sajatovic M, Alexopoulos GS, Burke J, Farahmand K, Siegert S. The effects of valbenazine on tardive dyskinesia in older and younger patients. Int J Geriatr Psychiatry. 2020 Jan;35(1):69-79. doi: 10.1002/gps.5218. Epub 2019 Oct 31.
Results Reference
derived
PubMed Identifier
28404690
Citation
Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites. J Pharmacol Exp Ther. 2017 Jun;361(3):454-461. doi: 10.1124/jpet.116.239160. Epub 2017 Apr 12.
Results Reference
derived
Learn more about this trial
NBI-98854 Dose Titration Study for the Treatment of Tardive Dyskinesia
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