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

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ClinicalTrials.gov Identifier: NCT01688037
Recruitment Status : Completed
First Posted : September 19, 2012
Results First Posted : November 8, 2017
Last Update Posted : November 8, 2017
Sponsor:
Information provided by (Responsible Party):
Neurocrine Biosciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Tardive Dyskinesia
Interventions Drug: NBI-98854
Drug: Placebo
Enrollment 109
Recruitment Details This study enrolled patients with a clinical diagnosis of schizophrenia or schizoaffective disorder with moderate or severe tardive dyskinesia (TD) from 35 centers in the United States and Puerto Rico. The last patient completed in October 2013.
Pre-assignment Details  
Arm/Group Title Double-Blind Placebo, Then Open-Label 50mg Double-Blind 50mg, Then Open-Label 50mg Double-Blind 100mg/50mg, Then Open-Label 50mg
Hide Arm/Group Description

Double-Blind Period: Participants first received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.

Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.

Double-Blind Period: Participants first received valbenazine 50mg capsule once daily for 6 weeks.

Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.

Double-Blind Period: Participants first received valbenazine 100mg capsule once daily for 2 weeks, then they received valbenazine 50mg capsule once daily for 4 weeks.

Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.

Period Title: Double-Blind Period (Week 0 to 6)
Started 54 28 27
Completed 47 25 21
Not Completed 7 3 6
Reason Not Completed
Adverse Event             1             0             1
Non-compliance             1             2             3
Withdrawal by Subject             4             0             1
Lost to Follow-up             1             0             1
Physician Decision             0             1             0
Period Title: Open-Label Period (Week 6 to 12)
Started 47 25 21
Completed 42 22 17
Not Completed 5 3 4
Reason Not Completed
Adverse Event             4             1             1
Non-compliance             0             0             2
Withdrawal by Subject             1             2             0
Lost to Follow-up             0             0             1
Period Title: Follow-up Period (Week 12 to 16)
Started 42 22 17
Completed 42 21 17
Not Completed 0 1 0
Reason Not Completed
Withdrawal by Subject             0             1             0
Arm/Group Title Double-Blind Placebo, Then Open-Label 50mg Double-Blind 50mg, Then Open-Label 50mg Double-Blind 100mg/50mg, Then Open-Label 50mg Total
Hide Arm/Group Description

Double-Blind Period: Participants first received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.

Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.

Double-Blind Period: Participants first received valbenazine 50mg capsule once daily for 6 weeks.

Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.

Double-Blind Period: Participants first received valbenazine 100mg capsule once daily for 2 weeks, then they received valbenazine 50mg capsule once daily for 4 weeks.

Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.

Total of all reporting groups
Overall Number of Baseline Participants 54 28 27 109
Hide Baseline Analysis Population Description
Safety analysis set (all randomized subjects who received at least 1 dose of study drug).
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 54 participants 28 participants 27 participants 109 participants
54.5
(27 to 76)
55.5
(42 to 72)
55.6
(28 to 77)
55.0
(27 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants 28 participants 27 participants 109 participants
Female
20
  37.0%
8
  28.6%
9
  33.3%
37
  33.9%
Male
34
  63.0%
20
  71.4%
18
  66.7%
72
  66.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Black or African American Number Analyzed 54 participants 28 participants 27 participants 109 participants
29
  53.7%
12
  42.9%
7
  25.9%
48
  44.0%
White Number Analyzed 54 participants 28 participants 27 participants 109 participants
23
  42.6%
15
  53.6%
19
  70.4%
57
  52.3%
Native Hawaiian or Other Pacific Islander Number Analyzed 54 participants 28 participants 27 participants 109 participants
1
   1.9%
0
   0.0%
0
   0.0%
1
   0.9%
Other Number Analyzed 54 participants 28 participants 27 participants 109 participants
0
   0.0%
1
   3.6%
0
   0.0%
1
   0.9%
American Indian or Alaska Native, Black Number Analyzed 54 participants 28 participants 27 participants 109 participants
1
   1.9%
0
   0.0%
1
   3.7%
2
   1.8%
Body Mass Index  
Mean (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 54 participants 28 participants 27 participants 109 participants
28.71
(19.2 to 44.2)
28.85
(18.5 to 42.6)
26.39
(14.1 to 37.8)
28.17
(14.1 to 44.2)
Age at Schizophrenia/Schizoaffective Disorder Diagnosis   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 50 participants 27 participants 25 participants 102 participants
29.4
(10 to 68)
29.7
(16 to 66)
30.4
(17 to 66)
29.7
(10 to 68)
[1]
Measure Analysis Population Description: Date of diagnosis was not available for some subjects.
Age at TD Diagnosis   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 49 participants 26 participants 22 participants 97 participants
46.9
(16 to 73)
48.5
(37 to 67)
47.5
(22 to 73)
47.5
(16 to 73)
[1]
Measure Analysis Population Description: Date of diagnosis was not available for some subjects.
BPRS Total Score   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 54 participants 28 participants 27 participants 109 participants
33.8
(20 to 48)
32.6
(22 to 49)
33.0
(21 to 49)
33.3
(20 to 49)
[1]
Measure Description: The Brief Psychiatric Rating Scale (BPRS) is a clinician-rated tool designed to assess change in the severity of psychopathology in patients with schizophrenia and other psychotic disorders (Overall and Gorham, 1962, 1988). The severity of each of the 18 items of the BPRS is rated on a scale of 1 (not present) to 7 (extremely severe) (total score range: 18 to 126). Higher scores represent greater symptom severity.
Baseline AIMS Total Dyskinesia Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 54 participants 27 participants 26 participants 107 participants
15.3  (4.4) 14.6  (5.9) 14.6  (4.7) 15.0  (4.8)
[1]
Measure 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.
[2]
Measure Analysis Population Description: Baseline AIMS Total Dyskinesia Score based on the ITT analysis set.
1.Primary Outcome
Title Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
Hide 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. The primary efficacy endpoint was the change from baseline in the AIMS dyskinesia total score at Week 6 between the pooled NBI-98854 50+100 mg group and placebo group analyzed using the ANCOVA model (LOCF, ITT analysis set).
Time Frame Baseline and Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at either Week 2 or Week 6). Last observation carried forward (LOCF) imputation method.
Arm/Group Title Placebo All Valbenazine
Hide Arm/Group Description:
Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.
Includes participants who received valbenazine 50mg capsule once daily for 6 weeks and participants who received valbenazine 100mg capsule once daily for 2 weeks, then 50mg capsule once daily for 4 weeks (a total of 6 weeks).
Overall Number of Participants Analyzed 54 50
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.5  (0.7) -3.3  (0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, All Valbenazine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2966
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.3 to 0.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.8
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). The ANOVA analysis of CGI-TD was conducted for the pooled NBI-98854 50+100 mg group and placebo group.
Time Frame Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at either Week 2 or Week 6).
Arm/Group Title Placebo Valbenazine 50mg and Valbenazine 100mg Then 50mg
Hide Arm/Group Description:
Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.
Includes participants who received valbenazine 50mg capsule once daily for 6 weeks and participants who received valbenazine 100mg capsule once daily for 2 weeks, then 50mg capsule once daily for 4 weeks (a total of 6 weeks).
Overall Number of Participants Analyzed 54 50
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.2  (0.1) 3.3  (0.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Valbenazine 50mg and Valbenazine 100mg Then 50mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.743
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 2
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 Week 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at Week 2).
Arm/Group Title Placebo Valbenazine 50mg Valbenazine 100mg
Hide Arm/Group Description:
Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.
Participants received valbenazine 50mg capsule once daily for 2 weeks.
Participants received valbenazine 100mg capsule once daily for 2 weeks.
Overall Number of Participants Analyzed 53 27 26
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.6  (0.1) 3.3  (0.2) 3.2  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Valbenazine 50mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1151
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.7 to 0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Valbenazine 100mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0277
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%
-0.8 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2
Estimation Comments [Not Specified]
Time Frame Up to 16 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Double-Blind 50mg Double-Blind 100mg/50mg Double-Blind Placebo Open-Label 50mg Follow-Up
Hide Arm/Group Description Double-Blind Period: Participants received valbenazine 50mg capsule once daily for 6 weeks. Double-Blind Period: Participants received valbenazine 100mg capsule once daily for 2 weeks, then they received valbenazine 50mg capsule once daily for 4 weeks. Double-Blind Period: Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks. Open-Label Period: Participants who completed the double-blind period entered the open-label period to receive valbenazine 50mg capsule for an additional 6 weeks of treatment. Participants who completed the open-label period entered the 4-week follow-up period.
All-Cause Mortality
Double-Blind 50mg Double-Blind 100mg/50mg Double-Blind Placebo Open-Label 50mg Follow-Up
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/28 (0.00%)      0/27 (0.00%)      0/54 (0.00%)      0/93 (0.00%)      0/80 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Double-Blind 50mg Double-Blind 100mg/50mg Double-Blind Placebo Open-Label 50mg Follow-Up
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/28 (7.14%)      0/27 (0.00%)      1/54 (1.85%)      3/93 (3.23%)      0/80 (0.00%)    
General disorders           
Chest pain * 1  1/28 (3.57%)  0/27 (0.00%)  0/54 (0.00%)  0/93 (0.00%)  0/80 (0.00%) 
Infections and infestations           
Bronchitis * 1  0/28 (0.00%)  0/27 (0.00%)  0/54 (0.00%)  1/93 (1.08%)  0/80 (0.00%) 
Injury, poisoning and procedural complications           
Fall * 1  1/28 (3.57%)  0/27 (0.00%)  0/54 (0.00%)  0/93 (0.00%)  0/80 (0.00%) 
Psychiatric disorders           
Schizoaffective disorder * 1  0/28 (0.00%)  0/27 (0.00%)  0/54 (0.00%)  1/93 (1.08%)  0/80 (0.00%) 
Schizophrenia, paranoid type * 1  0/28 (0.00%)  0/27 (0.00%)  1/54 (1.85%)  0/93 (0.00%)  0/80 (0.00%) 
Schizophrenia * 1  0/28 (0.00%)  0/27 (0.00%)  0/54 (0.00%)  1/93 (1.08%)  0/80 (0.00%) 
Suicidal ideation * 1  0/28 (0.00%)  0/27 (0.00%)  0/54 (0.00%)  1/93 (1.08%)  0/80 (0.00%) 
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%
Double-Blind 50mg Double-Blind 100mg/50mg Double-Blind Placebo Open-Label 50mg Follow-Up
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/28 (14.29%)      3/27 (11.11%)      2/54 (3.70%)      5/93 (5.38%)      1/80 (1.25%)    
General disorders           
Fatigue * 1  0/28 (0.00%)  0 2/27 (7.41%)  2 0/54 (0.00%)  0 0/93 (0.00%)  0 0/80 (0.00%)  0
Infections and infestations           
Urinary tract infection * 1  0/28 (0.00%)  0 1/27 (3.70%)  1 2/54 (3.70%)  2 5/93 (5.38%)  5 0/80 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  2/28 (7.14%)  2 0/27 (0.00%)  0 0/54 (0.00%)  0 0/93 (0.00%)  0 1/80 (1.25%)  1
Nervous system disorders           
Somnolence * 1  2/28 (7.14%)  2 1/27 (3.70%)  1 0/54 (0.00%)  0 0/93 (0.00%)  0 0/80 (0.00%)  0
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: NCT01688037     History of Changes
Other Study ID Numbers: NBI-98854-1201
First Submitted: September 11, 2012
First Posted: September 19, 2012
Results First Submitted: May 11, 2017
Results First Posted: November 8, 2017
Last Update Posted: November 8, 2017