Trial Outcomes & Findings for The Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine (NCT NCT03698331)
NCT ID: NCT03698331
Last Updated: 2020-06-04
Results Overview
A withdrawal-emergent adverse event is an adverse event that begins during the Withdrawal Period.
COMPLETED
PHASE4
89 participants
3 weeks
2020-06-04
Participant Flow
Participant milestones
| Measure |
Valbenazine/Placebo
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
44
|
45
|
|
Overall Study
Entered Withdrawal Period
|
42
|
39
|
|
Overall Study
COMPLETED
|
40
|
39
|
|
Overall Study
NOT COMPLETED
|
4
|
6
|
Reasons for withdrawal
| Measure |
Valbenazine/Placebo
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
|
Overall Study
Non-compliance with study drug
|
1
|
0
|
Baseline Characteristics
The Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine
Baseline characteristics by cohort
| Measure |
Valbenazine/Placebo
n=44 Participants
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=45 Participants
Placebo administered once daily for 7 weeks.
|
Total
n=89 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.7 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
53.6 years
STANDARD_DEVIATION 9.5 • n=7 Participants
|
54.1 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
19 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
25 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
13 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
30 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 weeksPopulation: Dependence and Withdrawal Analysis Set, which includes all participants who were randomized, took at least one dose of study drug, and entered the Withdrawal Period.
A withdrawal-emergent adverse event is an adverse event that begins during the Withdrawal Period.
Outcome measures
| Measure |
Valbenazine/Placebo
n=42 Participants
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=39 Participants
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Participants With Withdrawal-Emergent Adverse Events
|
9 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: 3 weeksPopulation: Dependence and Withdrawal Analysis Set, which includes all participants who were randomized, took at least one dose of study drug, and entered the Withdrawal Period.
The PWC-20 is a validated 20-item physician-rated survey that assesses the severity of potential symptoms of withdrawal. Items are rated on a scale from 0 to 3, with total scores ranging from 0 to 60. Worsening of symptoms is defined by 5 new symptoms of moderate or severe degree or a worsening of symptoms by 2 points on the PWC-20 scale during Weeks 5 to 7 compared with Week 4. Note: a 2-point worsening from 0 (none) at Week 4 to 2 (moderate) post-Week 4 is counted as a worsening of symptoms.
Outcome measures
| Measure |
Valbenazine/Placebo
n=42 Participants
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=39 Participants
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Participants Who Experience Worsening of Symptoms as Measured by the Physician Withdrawal Checklist-20 (PWC-20)
|
9 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 3 weeksPopulation: Dependence and Withdrawal Analysis Set, which includes all participants who were randomized, took at least one dose of study drug, and entered the Withdrawal Period.
The PWC-20 is a validated 20-item physician-rated survey that assesses the severity of potential symptoms of withdrawal. Items are rated on a scale from 0 to 3, with total scores ranging from 0 to 60. Larger values indicate more severe symptoms. Rickels et al (J Clin Psychopharmacol 2008) cites PWC-20 mean scores associated with withdrawal in the range of 15 to 24.
Outcome measures
| Measure |
Valbenazine/Placebo
n=42 Participants
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=39 Participants
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Absolute Worst Total Score as Measured by the Physician Withdrawal Checklist-20 (PWC-20)
Mean absolute score at baseline
|
4.6 score on a scale
Standard Deviation 5.0
|
3.9 score on a scale
Standard Deviation 4.5
|
|
Absolute Worst Total Score as Measured by the Physician Withdrawal Checklist-20 (PWC-20)
Mean absolute score at withdrawal baseline
|
3.8 score on a scale
Standard Deviation 3.7
|
3.1 score on a scale
Standard Deviation 3.8
|
|
Absolute Worst Total Score as Measured by the Physician Withdrawal Checklist-20 (PWC-20)
Mean absolute worst total score
|
5.6 score on a scale
Standard Deviation 5.3
|
3.3 score on a scale
Standard Deviation 2.6
|
SECONDARY outcome
Timeframe: 7 weeksPopulation: Dependence and Withdrawal Analysis Set, which includes all participants who were randomized, took at least one dose of study drug, and entered the Withdrawal Period.
The mCSSA is an 18-item survey based on symptoms commonly associated with early cocaine abstinence, including depression, fatigue, anhedonia, anxiety, irritability, sleep disturbance, and inability to concentrate. Items are rated on scales of 0 to 7 or 0 to 8, with separate scale descriptions for each item. Larger values indicate more severe symptoms. The scale has been modified to be specific to study drug (valbenazine or placebo) instead of cocaine.
Outcome measures
| Measure |
Valbenazine/Placebo
n=42 Participants
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=39 Participants
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Severity of Withdrawal Symptoms as Measured by the Change From Withdrawal Baseline (Week 4) to Week 7 in the Modified Cocaine Selective Severity Assessment (mCSSA)
|
1.9 score on a scale
Standard Deviation 4.1
|
0.5 score on a scale
Standard Deviation 3.2
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 7Population: Efficacy analysis set was defined as all participants who were randomized to a treatment group, took at least one dose of study drug, and had a CGI-TD-I assessment at Week 4.
The CGI-TD-I scale is a 7-point scale (range; 1=very much improved to 7=very much worse) used to assess overall improvement in TD symptoms since the initiation of study drug dosing.
Outcome measures
| Measure |
Valbenazine/Placebo
n=41 Participants
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=40 Participants
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Overall Improvement From Baseline of TD Symptoms as Measured by the Clinical Global Impression-Tardive Dyskinesia-Improvement (CGI-TD-I) Score
End of Week 4
|
3.2 score on a scale
Standard Deviation 0.8
|
3.4 score on a scale
Standard Deviation 0.7
|
|
Overall Improvement From Baseline of TD Symptoms as Measured by the Clinical Global Impression-Tardive Dyskinesia-Improvement (CGI-TD-I) Score
End of Week 7
|
3.0 score on a scale
Standard Deviation 0.7
|
3.0 score on a scale
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 7Population: Efficacy analysis set was defined as all participants who were randomized to a treatment group, took at least one dose of study drug, and had a CGI-TD-S assessment at Week 4.
The CGI-TD-S scale is a 7-point scale (range; 1=normal, not at all ill to 7=among the most extremely ill patient) used to assess the overall global severity of TD.
Outcome measures
| Measure |
Valbenazine/Placebo
n=41 Participants
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=40 Participants
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Change in Severity of TD Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Tardive Dyskinesia-Severity (CGI-TD-S) Scale
End of Week 4
|
-0.3 score on a scale
Standard Deviation 0.7
|
-0.2 score on a scale
Standard Deviation 0.6
|
|
Change in Severity of TD Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Tardive Dyskinesia-Severity (CGI-TD-S) Scale
End of Week 5
|
-0.3 score on a scale
Standard Deviation 0.6
|
-0.3 score on a scale
Standard Deviation 0.6
|
|
Change in Severity of TD Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Tardive Dyskinesia-Severity (CGI-TD-S) Scale
End of Week 6
|
-0.4 score on a scale
Standard Deviation 0.5
|
-0.5 score on a scale
Standard Deviation 0.6
|
|
Change in Severity of TD Symptoms as Measured by Change From Baseline in the Clinical Global Impression-Tardive Dyskinesia-Severity (CGI-TD-S) Scale
End of Week 7
|
-0.4 score on a scale
Standard Deviation 0.5
|
-0.5 score on a scale
Standard Deviation 0.6
|
Adverse Events
Valbenazine/Placebo
Placebo/Placebo
Serious adverse events
| Measure |
Valbenazine/Placebo
n=44 participants at risk
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=45 participants at risk
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Psychiatric disorders
Schizoaffective disorder
|
2.3%
1/44 • Up to 7 weeks
|
0.00%
0/45 • Up to 7 weeks
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/44 • Up to 7 weeks
|
2.2%
1/45 • Up to 7 weeks
|
Other adverse events
| Measure |
Valbenazine/Placebo
n=44 participants at risk
Valbenazine administered once daily for 4 weeks, followed by placebo administered once daily for 3 weeks.
|
Placebo/Placebo
n=45 participants at risk
Placebo administered once daily for 7 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
11.4%
5/44 • Up to 7 weeks
|
4.4%
2/45 • Up to 7 weeks
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
4.5%
2/44 • Up to 7 weeks
|
0.00%
0/45 • Up to 7 weeks
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
2/44 • Up to 7 weeks
|
4.4%
2/45 • Up to 7 weeks
|
|
Gastrointestinal disorders
Nausea
|
2.3%
1/44 • Up to 7 weeks
|
8.9%
4/45 • Up to 7 weeks
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/44 • Up to 7 weeks
|
4.4%
2/45 • Up to 7 weeks
|
|
Nervous system disorders
Dizziness
|
4.5%
2/44 • Up to 7 weeks
|
2.2%
1/45 • Up to 7 weeks
|
|
Nervous system disorders
Headache
|
4.5%
2/44 • Up to 7 weeks
|
11.1%
5/45 • Up to 7 weeks
|
|
Nervous system disorders
Somnolence
|
4.5%
2/44 • Up to 7 weeks
|
2.2%
1/45 • Up to 7 weeks
|
|
Eye disorders
Dry eye
|
4.5%
2/44 • Up to 7 weeks
|
2.2%
1/45 • Up to 7 weeks
|
|
General disorders
Fatigue
|
4.5%
2/44 • Up to 7 weeks
|
0.00%
0/45 • Up to 7 weeks
|
|
Infections and infestations
Nasopharyngitis
|
2.3%
1/44 • Up to 7 weeks
|
4.4%
2/45 • Up to 7 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
2.3%
1/44 • Up to 7 weeks
|
8.9%
4/45 • Up to 7 weeks
|
|
Psychiatric disorders
Anxiety
|
2.3%
1/44 • Up to 7 weeks
|
4.4%
2/45 • Up to 7 weeks
|
|
Vascular disorders
Hypertension
|
0.00%
0/44 • Up to 7 weeks
|
4.4%
2/45 • Up to 7 weeks
|
Additional Information
Neurocrine Medical Information
Neurocrine Biosciences, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place