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NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder

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ClinicalTrials.gov Identifier: NCT01393600
Recruitment Status : Completed
First Posted : July 13, 2011
Results First Posted : August 10, 2017
Last Update Posted : August 10, 2017
Sponsor:
Information provided by (Responsible Party):
Neurocrine Biosciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Tardive Dyskinesia
Interventions Drug: NBI-98854
Drug: Placebo
Enrollment 37
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.
Pre-assignment Details  
Arm/Group Title Placebo, Then Valbenazine 12.5 mg Valbenazine 12.5 mg, Then Placebo Placebo, Then Valbenazine 50 mg Valbenazine 50 mg, Then Placebo
Hide Arm/Group Description Participants first received Placebo (matching valbenazine solution) once daily from Day 1 to 14, then they received valbenazine 12.5 mg solution once daily from Day 15 to 28. Participants first received valbenazine 12.5 mg solution once daily from Day 1 to 14, then they received Placebo (matching valbenazine solution) once daily from Day 15 to 28. Participants first received Placebo (matching valbenazine solution) once daily from Day 1 to 14, then they received valbenazine 50 mg solution once daily from Day 15 to 28. Participants first received valbenazine 50 mg solution once daily from Day 1 to 14, then they received Placebo (matching valbenazine solution) once daily from Day 15 to 28.
Period Title: Treatment Period 1 (Day 1 to 14)
Started 9 8 10 10
Completed 9 7 9 9
Not Completed 0 1 1 1
Reason Not Completed
Protocol Violation             0             1             0             0
Withdrawal by Subject             0             0             1             0
Adverse Event             0             0             0             1
Period Title: Treatment Period 2 (Day 15 to 28)
Started 9 7 9 9
Completed 9 7 7 8
Not Completed 0 0 2 1
Reason Not Completed
Withdrawal by Subject             0             0             0             1
Lost to Follow-up             0             0             1             0
Physician Decision             0             0             1             0
Period Title: Follow-up Period (Day 29 to 35)
Started 9 7 7 8
Completed 9 7 6 8
Not Completed 0 0 1 0
Reason Not Completed
Withdrawal by Subject             0             0             1             0
Arm/Group Title All Subjects
Hide Arm/Group Description All randomized subjects who received at least one dose of study drug.
Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 37 participants
51.1
(29 to 65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
15
  40.5%
Male
22
  59.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Black
12
  32.4%
Caucasian
15
  40.5%
Hispanic
10
  27.0%
Body Mass Index  
Mean (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 37 participants
29.9
(18.1 to 42.0)
Age of Schizophrenia/Schizoaffective Disorder Diagnosis  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 37 participants
25.8
(8 to 54)
Age at TD Diagnosis  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 37 participants
41.7
(18 to 63)
1.Primary Outcome
Title Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score
Hide 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 Day 15 and 29, averaged
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Valbenazine 12.5 mg Valbenazine 50 mg
Hide Arm/Group Description:
Placebo (matching valbenazine solution)
Valbenazine 12.5 mg solution
Valbenazine 50 mg solution
Overall Number of Participants Analyzed 33 17 15
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
9.9  (0.7) 9.1  (1.2) 8.8  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Valbenazine 12.5 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5880
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-3.3 to 1.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Valbenazine 50 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4184
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-3.8 to 1.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.3
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Clinical Global Impression - Global Improvement of TD (CGI-TD)
Hide 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 Day 15 and 29, averaged
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Valbenazine 12.5mg Placebo Valbenazine 12.5mg Valbenazine 50mg Placebo Valbenazine 50mg
Hide Arm/Group Description:
Participants who received Placebo (matching valbenazine 12.5mg solution) once daily from Day 1 to 14 and participants who received Placebo (matching valbenazine 12.5mg solution) from Day 15 to 28.
Participants who received valbenazine 12.5mg solution once daily from Day 1 to 14 and participants who received valbenazine 12.5mg solution from Day 15 to 28.
Participants who received Placebo (matching valbenazine 50mg solution) once daily from Day 1 to 14 and participants who received Placebo (matching valbenazine 50mg solution) from Day 15 to 28.
Participants who received valbenazine 50mg solution once daily from Day 1 to 14 and participants who received valbenazine 50mg solution from Day 15 to 28.
Overall Number of Participants Analyzed 16 17 17 15
Mean (Standard Error)
Unit of Measure: units on a scale
2.2  (0.2) 2.2  (0.2) 3.2  (0.3) 2.6  (0.3)
3.Post-Hoc Outcome
Title Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score for Combined NBI-98854 Dose Groups (Excluding 1 Site)
Hide 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 Day 15 and 29, averaged
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Valbenazine 12.5 mg Valbenazine 50 mg
Hide Arm/Group Description:
Placebo (matching valbenazine solution)
Valbenazine 12.5 mg solution
Valbenazine 50 mg solution
Overall Number of Participants Analyzed 26 15 10
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
10.3  (0.9) 9.9  (1.1) 6.1  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Valbenazine 12.5 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6761
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-2.4 to 1.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Valbenazine 50 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.2
Confidence Interval (2-Sided) 95%
-6.6 to -1.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.1
Estimation Comments [Not Specified]
Time Frame up to 35 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo NBI-98854 12.5 mg NBI-98854 50 mg
Hide Arm/Group Description Placebo (matching NBI-98854 solution) for 28 days followed by 7 days of posttreatment. NBI-98854 12.5 mg solution for 28 days followed by 7 days of posttreatment. NBI-98854 50 mg solution for 28 days followed by 7 days of posttreatment.
All-Cause Mortality
Placebo NBI-98854 12.5 mg NBI-98854 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)      0/17 (0.00%)      0/19 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo NBI-98854 12.5 mg NBI-98854 50 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/35 (0.00%)      1/17 (5.88%)      0/19 (0.00%)    
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease * 1  0/35 (0.00%)  0 1/17 (5.88%)  1 0/19 (0.00%)  0
1
Term from vocabulary, MedDRA (12.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo NBI-98854 12.5 mg NBI-98854 50 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/35 (11.43%)      4/17 (23.53%)      6/19 (31.58%)    
Eye disorders       
Vision blurred * 1  0/35 (0.00%)  0 0/17 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal disorders       
Diarrhoea * 1  2/35 (5.71%)  4 1/17 (5.88%)  1 0/19 (0.00%)  0
Vomiting * 1  0/35 (0.00%)  0 1/17 (5.88%)  1 0/19 (0.00%)  0
General disorders       
Fatigue * 1  2/35 (5.71%)  2 0/17 (0.00%)  0 0/19 (0.00%)  0
Infections and infestations       
Furuncle * 1  0/35 (0.00%)  0 1/17 (5.88%)  1 1/19 (5.26%)  1
Gastroenteritis viral * 1  0/35 (0.00%)  0 0/17 (0.00%)  0 1/19 (5.26%)  1
Investigations       
Blood creatine phosphokinase increased * 1  0/35 (0.00%)  0 0/17 (0.00%)  0 1/19 (5.26%)  1
Urine analysis abnormal * 1  0/35 (0.00%)  0 1/17 (5.88%)  1 0/19 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back pain * 1  2/35 (5.71%)  2 1/17 (5.88%)  1 0/19 (0.00%)  0
Musculoskeletal stiffness * 1  0/35 (0.00%)  0 1/17 (5.88%)  1 0/19 (0.00%)  0
Nervous system disorders       
Akathisia * 1  0/35 (0.00%)  0 0/17 (0.00%)  0 1/19 (5.26%)  1
Headache * 1  2/35 (5.71%)  5 1/17 (5.88%)  1 0/19 (0.00%)  0
Paraesthesia * 1  0/35 (0.00%)  0 1/17 (5.88%)  1 0/19 (0.00%)  0
Sedation * 1  1/35 (2.86%)  1 0/17 (0.00%)  0 1/19 (5.26%)  1
Somnolence * 1  0/35 (0.00%)  0 0/17 (0.00%)  0 1/19 (5.26%)  1
Psychiatric disorders       
Restlessness * 1  0/35 (0.00%)  0 0/17 (0.00%)  0 1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders       
Cough * 1  0/35 (0.00%)  0 0/17 (0.00%)  0 1/19 (5.26%)  1
Skin and subcutaneous tissue disorders       
Pruritis * 1  0/35 (0.00%)  0 0/17 (0.00%)  0 1/19 (5.26%)  1
1
Term from vocabulary, MedDRA (12.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Generally, the PI has the right to publish results provided such publication does not violate confidentiality or IP provisions within the contract with the Sponsor. Prior to submission for publication or presentation of results, the PI must provide the Sponsor time for review. The Sponsor can request the PI to withhold or remove information from all publications. For a multi-center study, any publication of results by the PI shall not be made before the first multi-center publication.
Results Point of Contact
Name/Title: Neurocrine Medical Information
Organization: Neurocrine Biosciences, Inc.
Phone: 877-641-3461
Responsible Party: Neurocrine Biosciences
ClinicalTrials.gov Identifier: NCT01393600     History of Changes
Other Study ID Numbers: NBI-98854-1101
First Submitted: July 11, 2011
First Posted: July 13, 2011
Results First Submitted: May 11, 2017
Results First Posted: August 10, 2017
Last Update Posted: August 10, 2017