Trial Outcomes & Findings for NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder (KINECT Study) (NCT NCT01688037)
NCT ID: NCT01688037
Last Updated: 2017-11-08
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
109 participants
Primary outcome timeframe
Baseline and Week 6
Results posted on
2017-11-08
Participant Flow
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.
Participant milestones
| Measure |
Double-Blind Placebo, Then Open-Label 50mg
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 50mg, Then Open-Label 50mg
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 100mg/50mg, Then Open-Label 50mg
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.
|
|---|---|---|---|
|
Double-Blind Period (Week 0 to 6)
STARTED
|
54
|
28
|
27
|
|
Double-Blind Period (Week 0 to 6)
COMPLETED
|
47
|
25
|
21
|
|
Double-Blind Period (Week 0 to 6)
NOT COMPLETED
|
7
|
3
|
6
|
|
Open-Label Period (Week 6 to 12)
STARTED
|
47
|
25
|
21
|
|
Open-Label Period (Week 6 to 12)
COMPLETED
|
42
|
22
|
17
|
|
Open-Label Period (Week 6 to 12)
NOT COMPLETED
|
5
|
3
|
4
|
|
Follow-up Period (Week 12 to 16)
STARTED
|
42
|
22
|
17
|
|
Follow-up Period (Week 12 to 16)
COMPLETED
|
42
|
21
|
17
|
|
Follow-up Period (Week 12 to 16)
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Double-Blind Placebo, Then Open-Label 50mg
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 50mg, Then Open-Label 50mg
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 100mg/50mg, Then Open-Label 50mg
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.
|
|---|---|---|---|
|
Double-Blind Period (Week 0 to 6)
Adverse Event
|
1
|
0
|
1
|
|
Double-Blind Period (Week 0 to 6)
Non-compliance
|
1
|
2
|
3
|
|
Double-Blind Period (Week 0 to 6)
Withdrawal by Subject
|
4
|
0
|
1
|
|
Double-Blind Period (Week 0 to 6)
Lost to Follow-up
|
1
|
0
|
1
|
|
Double-Blind Period (Week 0 to 6)
Physician Decision
|
0
|
1
|
0
|
|
Open-Label Period (Week 6 to 12)
Adverse Event
|
4
|
1
|
1
|
|
Open-Label Period (Week 6 to 12)
Non-compliance
|
0
|
0
|
2
|
|
Open-Label Period (Week 6 to 12)
Withdrawal by Subject
|
1
|
2
|
0
|
|
Open-Label Period (Week 6 to 12)
Lost to Follow-up
|
0
|
0
|
1
|
|
Follow-up Period (Week 12 to 16)
Withdrawal by Subject
|
0
|
1
|
0
|
Baseline Characteristics
Date of diagnosis was not available for some subjects.
Baseline characteristics by cohort
| Measure |
Double-Blind Placebo, Then Open-Label 50mg
n=54 Participants
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 50mg, Then Open-Label 50mg
n=28 Participants
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 100mg/50mg, Then Open-Label 50mg
n=27 Participants
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
n=109 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.5 years
n=54 Participants
|
55.5 years
n=28 Participants
|
55.6 years
n=27 Participants
|
55.0 years
n=109 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=54 Participants
|
8 Participants
n=28 Participants
|
9 Participants
n=27 Participants
|
37 Participants
n=109 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=54 Participants
|
20 Participants
n=28 Participants
|
18 Participants
n=27 Participants
|
72 Participants
n=109 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
29 Participants
n=54 Participants
|
12 Participants
n=28 Participants
|
7 Participants
n=27 Participants
|
48 Participants
n=109 Participants
|
|
Race/Ethnicity, Customized
White
|
23 Participants
n=54 Participants
|
15 Participants
n=28 Participants
|
19 Participants
n=27 Participants
|
57 Participants
n=109 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=54 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=109 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=54 Participants
|
1 Participants
n=28 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=109 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native, Black
|
1 Participants
n=54 Participants
|
0 Participants
n=28 Participants
|
1 Participants
n=27 Participants
|
2 Participants
n=109 Participants
|
|
Body Mass Index
|
28.71 kg/m^2
n=54 Participants
|
28.85 kg/m^2
n=28 Participants
|
26.39 kg/m^2
n=27 Participants
|
28.17 kg/m^2
n=109 Participants
|
|
Age at Schizophrenia/Schizoaffective Disorder Diagnosis
|
29.4 years
n=50 Participants • Date of diagnosis was not available for some subjects.
|
29.7 years
n=27 Participants • Date of diagnosis was not available for some subjects.
|
30.4 years
n=25 Participants • Date of diagnosis was not available for some subjects.
|
29.7 years
n=102 Participants • Date of diagnosis was not available for some subjects.
|
|
Age at TD Diagnosis
|
46.9 years
n=49 Participants • Date of diagnosis was not available for some subjects.
|
48.5 years
n=26 Participants • Date of diagnosis was not available for some subjects.
|
47.5 years
n=22 Participants • Date of diagnosis was not available for some subjects.
|
47.5 years
n=97 Participants • Date of diagnosis was not available for some subjects.
|
|
BPRS Total Score
|
33.8 units on a scale
n=54 Participants
|
32.6 units on a scale
n=28 Participants
|
33.0 units on a scale
n=27 Participants
|
33.3 units on a scale
n=109 Participants
|
|
Baseline AIMS Total Dyskinesia Score
|
15.3 units on a scale
STANDARD_DEVIATION 4.4 • n=54 Participants • Baseline AIMS Total Dyskinesia Score based on the ITT analysis set.
|
14.6 units on a scale
STANDARD_DEVIATION 5.9 • n=27 Participants • Baseline AIMS Total Dyskinesia Score based on the ITT analysis set.
|
14.6 units on a scale
STANDARD_DEVIATION 4.7 • n=26 Participants • Baseline AIMS Total Dyskinesia Score based on the ITT analysis set.
|
15.0 units on a scale
STANDARD_DEVIATION 4.8 • n=107 Participants • Baseline AIMS Total Dyskinesia Score based on the ITT analysis set.
|
PRIMARY outcome
Timeframe: Baseline and Week 6Population: 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.
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).
Outcome measures
| Measure |
Placebo
n=54 Participants
Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.
|
All Valbenazine
n=50 Participants
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).
|
Valbenazine 100mg
Participants received valbenazine 100mg capsule once daily for 2 weeks.
|
|---|---|---|---|
|
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
|
-2.5 units on a scale
Standard Error 0.7
|
-3.3 units on a scale
Standard Error 0.7
|
—
|
SECONDARY outcome
Timeframe: Week 6Population: 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).
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.
Outcome measures
| Measure |
Placebo
n=54 Participants
Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.
|
All Valbenazine
n=50 Participants
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).
|
Valbenazine 100mg
Participants received valbenazine 100mg capsule once daily for 2 weeks.
|
|---|---|---|---|
|
Clinical Global Impression - Global Improvement of TD (CGI-TD)
|
3.2 units on a scale
Standard Error 0.1
|
3.3 units on a scale
Standard Error 0.1
|
—
|
SECONDARY outcome
Timeframe: Week 2Population: ITT analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at Week 2).
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).
Outcome measures
| Measure |
Placebo
n=53 Participants
Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.
|
All Valbenazine
n=27 Participants
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).
|
Valbenazine 100mg
n=26 Participants
Participants received valbenazine 100mg capsule once daily for 2 weeks.
|
|---|---|---|---|
|
Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 2
|
3.6 units on a scale
Standard Error 0.1
|
3.3 units on a scale
Standard Error 0.2
|
3.2 units on a scale
Standard Error 0.2
|
Adverse Events
Double-Blind 50mg
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Double-Blind 100mg/50mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Double-Blind Placebo
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Open-Label 50mg
Serious events: 3 serious events
Other events: 5 other events
Deaths: 0 deaths
Follow-Up
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Double-Blind 50mg
n=28 participants at risk
Double-Blind Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.
|
Double-Blind 100mg/50mg
n=27 participants at risk
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 Placebo
n=54 participants at risk
Double-Blind Period: Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.
|
Open-Label 50mg
n=93 participants at risk
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.
|
Follow-Up
n=80 participants at risk
Participants who completed the open-label period entered the 4-week follow-up period.
|
|---|---|---|---|---|---|
|
Psychiatric disorders
Schizoaffective disorder
|
0.00%
0/28 • Up to 16 weeks
|
0.00%
0/27 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
1.1%
1/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
3.6%
1/28 • Up to 16 weeks
|
0.00%
0/27 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
0.00%
0/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
|
Psychiatric disorders
Schizophrenia, paranoid type
|
0.00%
0/28 • Up to 16 weeks
|
0.00%
0/27 • Up to 16 weeks
|
1.9%
1/54 • Up to 16 weeks
|
0.00%
0/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
|
Infections and infestations
Bronchitis
|
0.00%
0/28 • Up to 16 weeks
|
0.00%
0/27 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
1.1%
1/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
|
Psychiatric disorders
Schizophrenia
|
0.00%
0/28 • Up to 16 weeks
|
0.00%
0/27 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
1.1%
1/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/28 • Up to 16 weeks
|
0.00%
0/27 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
1.1%
1/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
|
General disorders
Chest pain
|
3.6%
1/28 • Up to 16 weeks
|
0.00%
0/27 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
0.00%
0/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
Other adverse events
| Measure |
Double-Blind 50mg
n=28 participants at risk
Double-Blind Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.
|
Double-Blind 100mg/50mg
n=27 participants at risk
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 Placebo
n=54 participants at risk
Double-Blind Period: Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.
|
Open-Label 50mg
n=93 participants at risk
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.
|
Follow-Up
n=80 participants at risk
Participants who completed the open-label period entered the 4-week follow-up period.
|
|---|---|---|---|---|---|
|
General disorders
Fatigue
|
0.00%
0/28 • Up to 16 weeks
|
7.4%
2/27 • Number of events 2 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
0.00%
0/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/28 • Up to 16 weeks
|
3.7%
1/27 • Number of events 1 • Up to 16 weeks
|
3.7%
2/54 • Number of events 2 • Up to 16 weeks
|
5.4%
5/93 • Number of events 5 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.1%
2/28 • Number of events 2 • Up to 16 weeks
|
0.00%
0/27 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
0.00%
0/93 • Up to 16 weeks
|
1.2%
1/80 • Number of events 1 • Up to 16 weeks
|
|
Nervous system disorders
Somnolence
|
7.1%
2/28 • Number of events 2 • Up to 16 weeks
|
3.7%
1/27 • Number of events 1 • Up to 16 weeks
|
0.00%
0/54 • Up to 16 weeks
|
0.00%
0/93 • Up to 16 weeks
|
0.00%
0/80 • Up to 16 weeks
|
Additional Information
Neurocrine Medical Information
Neurocrine Biosciences, Inc.
Phone: 877-641-3461
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER