Back to resultsA Phase 3 Study of NBI-98854 for the Treatment of Tardive Dyskinesia (KINECT 3)
Primary Purpose
Tardive Dyskinesia
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
NBI-98854
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tardive Dyskinesia
Eligibility Criteria
Inclusion Criteria:
- 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.
- Female subjects must not be pregnant.
- Have one of the following clinical diagnoses for at least 3 months prior to screening: Schizophrenia or Schizoaffective Disorder, or Mood Disorder.
- Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months prior to screening.
- Have moderate or severe TD.
- If using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder, be on stable doses.
- Be in good general health.
- Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
- Have a negative drug screen for amphetamines,barbiturates, benzodiazepines, phencyclidine, cocaine, opiates, or cannabinoids
Exclusion Criteria:
- Have an active, clinically significant unstable medical condition within 1 month prior to screening.
- Have a known history of substance dependence, or substance (drug) or alcohol abuse
- Have a significant risk of suicidal or violent behavior.
- Have a known history of neuroleptic malignant syndrome.
- Have a known history of long QT syndrome or cardiac tachy-arrhythmia.
- Have a cancer diagnosis within 3 years of screening (some exceptions allowed)
- Have received an investigational drug within 30 days prior to screening or plan to use an investigational drug (other than NBI-98854) during the study.
- Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline.
- Have an allergy, hypersensitivity, or intolerance to tetrabenazine.
- Have had previous exposure with NBI-98854 or had previously participated in an NBI-98854 clinical study.
- Are currently pregnant or breastfeeding.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
NBI-98854 40 mg
NBI-98854 80 mg
Placebo
Arm Description
NBI-98854 administered as one (1) 40 mg capsule and one (1) placebo capsule, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Subjects randomized to the NBI-98854 80 mg dose will receive NBI-98854 40 mg for the first week (administered as one (1) 40 mg capsule and one (1) placebo capsule), followed by NBI-98854 80 mg administered as two (2) 40 mg capsules, taken by mouth, every morning between 7:00am - 10:00am for 5 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Placebo administered as two (2) placebo capsules, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and be randomized to either a 40 mg or 80 mg dose. Subjects re-randomized to receive NBI-98854 80 mg will receive 40 mg for the first week.
Outcomes
Primary Outcome Measures
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
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 Outcome Measures
Clinical Global Impression of Change - 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).
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Responder Analysis at Week 6
Percentage of AIMS responders (subjects who had at least a 50 percent reduction in AIMS score from baseline)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02274558
Brief Title
A Phase 3 Study of NBI-98854 for the Treatment of Tardive Dyskinesia
Acronym
KINECT 3
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel, Fixed-Dose Study to Assess the Efficacy, Safety, and Tolerability of NBI-98854 for the Treatment of Tardive Dyskinesia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
July 2016 (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 administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.
Detailed Description
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel, fixed-dose study to evaluate the efficacy, safety, and tolerability of two doses of NBI-98854 (40 mg and 80 mg) compared to placebo, administered once daily. The study design includes a double-blind, placebo-controlled treatment period for 6 weeks and a double-blind NBI-98854 treatment period for an additional 42 weeks, for a total of 48 weeks of treatment. Final follow-up assessments will be conducted 4 weeks after the last dose of the study drug.
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 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
234 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NBI-98854 40 mg
Arm Type
Experimental
Arm Description
NBI-98854 administered as one (1) 40 mg capsule and one (1) placebo capsule, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Arm Title
NBI-98854 80 mg
Arm Type
Experimental
Arm Description
Subjects randomized to the NBI-98854 80 mg dose will receive NBI-98854 40 mg for the first week (administered as one (1) 40 mg capsule and one (1) placebo capsule), followed by NBI-98854 80 mg administered as two (2) 40 mg capsules, taken by mouth, every morning between 7:00am - 10:00am for 5 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Placebo administered as two (2) placebo capsules, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and be randomized to either a 40 mg or 80 mg dose. Subjects re-randomized to receive NBI-98854 80 mg will receive 40 mg for the first week.
Intervention Type
Drug
Intervention Name(s)
NBI-98854
Intervention Description
NBI-98854 40 mg capsules
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
NBI-98854 placebo capsules
Primary Outcome Measure Information:
Title
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
Description
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
Baseline and Week 6
Secondary Outcome Measure Information:
Title
Clinical Global Impression of Change - 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
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Responder Analysis at Week 6
Description
Percentage of AIMS responders (subjects who had at least a 50 percent reduction in AIMS score from baseline)
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:
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.
Female subjects must not be pregnant.
Have one of the following clinical diagnoses for at least 3 months prior to screening: Schizophrenia or Schizoaffective Disorder, or Mood Disorder.
Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months prior to screening.
Have moderate or severe TD.
If using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder, be on stable doses.
Be in good general health.
Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
Have a negative drug screen for amphetamines,barbiturates, benzodiazepines, phencyclidine, cocaine, opiates, or cannabinoids
Exclusion Criteria:
Have an active, clinically significant unstable medical condition within 1 month prior to screening.
Have a known history of substance dependence, or substance (drug) or alcohol abuse
Have a significant risk of suicidal or violent behavior.
Have a known history of neuroleptic malignant syndrome.
Have a known history of long QT syndrome or cardiac tachy-arrhythmia.
Have a cancer diagnosis within 3 years of screening (some exceptions allowed)
Have received an investigational drug within 30 days prior to screening or plan to use an investigational drug (other than NBI-98854) during the study.
Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline.
Have an allergy, hypersensitivity, or intolerance to tetrabenazine.
Have had previous exposure with NBI-98854 or had previously participated in an NBI-98854 clinical study.
Are currently pregnant or breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chris O'Brien, MD
Organizational Affiliation
Neurocrine Biosciences
Official's Role
Principal Investigator
Facility Information:
City
Little Rock
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Arkansas
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Anaheim
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Glendale
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Irvine
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San Diego
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Bradenton
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Hialeah
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Kissimmee
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Leesburg
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Maitland
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Miami
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Chicago
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Flowood
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Saint Louis
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Lincoln
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Amherst
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Cedarhurst
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Rochester
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Durham
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Pinehurst
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Dayton
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Shaker Heights
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Oklahoma City
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Conshohocken
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Norristown
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Phoenixville
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Scranton
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Charleston
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Memphis
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DeSoto
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Fort Worth
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Irving
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Petersburg
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Spokane
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Vancouver
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London
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Ontario
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Toronto
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Ontario
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Montreal
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Quebec
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Caguas
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Puerto Rico
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San Juan
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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
30695293
Citation
Correll CU, Cutler AJ, Kane JM, McEvoy JP, Liang GS, O'Brien CF. Characterizing Treatment Effects of Valbenazine for Tardive Dyskinesia: Additional Results From the KINECT 3 Study. J Clin Psychiatry. 2018 Dec 18;80(1):18m12278. doi: 10.4088/JCP.18m12278.
Results Reference
derived
PubMed Identifier
29141124
Citation
Factor SA, Remington G, Comella CL, Correll CU, Burke J, Jimenez R, Liang GS, O'Brien CF. The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-Year KINECT 3 Extension Study. J Clin Psychiatry. 2017 Nov/Dec;78(9):1344-1350. doi: 10.4088/JCP.17m11777.
Results Reference
derived
PubMed Identifier
28839342
Citation
Kane JM, Correll CU, Liang GS, Burke J, O'Brien CF. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder. Psychopharmacol Bull. 2017 Aug 1;47(3):69-76.
Results Reference
derived
PubMed Identifier
28839341
Citation
Josiassen RC, Kane JM, Liang GS, Burke J, O'Brien CF. Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. Psychopharmacol Bull. 2017 Aug 1;47(3):61-68.
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
PubMed Identifier
28320223
Citation
Hauser RA, Factor SA, Marder SR, Knesevich MA, Ramirez PM, Jimenez R, Burke J, Liang GS, O'Brien CF. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017 May 1;174(5):476-484. doi: 10.1176/appi.ajp.2017.16091037. Epub 2017 Mar 21.
Results Reference
derived
Learn more about this trial
A Phase 3 Study of NBI-98854 for the Treatment of Tardive Dyskinesia
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