Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome

• Sponsor: Neurocrine Biosciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03530293
• Collaborator: (none)
• Enrollment: 81
• Locations: 49
• Arms: 3
• Actual Duration (Months): 14.9
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 2, double-blind, placebo-controlled, randomized withdrawal study to evaluate the safety and maintenance of efficacy of an optimized once-daily (qd) dose of NBI-98854 in pediatric subjects with TS.

Condition or Disease	Intervention/Treatment	Phase
Tourette Syndrome	Drug: Valbenazine; Drug: Placebo oral capsule	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: open-label study drug treatment period followed by blinded randomization into treatment arm or placebo arm
• Primary Purpose: Treatment
• Official Title: A Phase 2, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study to Evaluate the Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome
• Actual Study Start Date: Apr 17, 2018
• Actual Primary Completion Date: Jul 16, 2019
• Actual Study Completion Date: Jul 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pre-randomization Valbenazine Participants received valbenazine once daily for up to 12 weeks, depending on if and when randomization occured. The starting dose was 20 mg for participants <50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for participants <50 kg and 80 mg for participants ≥50 kg to achieve an optimal dose of valbenazine for each participant.	Drug: Valbenazine; vesicular monoamine transporter 2 (VMAT2) inhibitor; Other Names: NBI-98854
Placebo Comparator: Randomized Placebo Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization.	Drug: Placebo oral capsule; non-active dosage form
Experimental: Randomized Valbenazine Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization.	Drug: Valbenazine; vesicular monoamine transporter 2 (VMAT2) inhibitor; Other Names: NBI-98854

Outcome Measures

Primary Outcome Measures

1. Time to Loss of Treatment Response [Randomization (Week 8, 10 or 12) through Week 36]

   Loss of treatment response during the withdrawal period was defined as: 2 consecutive visits with 1) an increase in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) of greater than 35% or 7 points from the randomized withdrawal period baseline and 2) an increase in CGI-Tics-Severity score of ≥2 points from the randomized withdrawal period baseline; or discontinuation due to lack of efficacy or a treatment-emergent adverse event (TEAE) of worsening of tics. Median (lower and upper quartiles) Kaplan-Meier estimates for the time to loss of treatment response were not able to be calculated because of the low incidence of loss of treatment response events.

Secondary Outcome Measures

1. Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the YGTSS TTS [Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization]

   The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity. Least-squares mean were estimated using a mixed-effects model for repeated measures.

2. Change From Randomization Baseline to the Week 36 Visit in the YGTSS TTS [Randomization Baseline (Week 8, 10 or 12); Week 36]

   The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity.

3. Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the CGI-Tics-Severity Score [Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization]

   The CGI-Tics-Severity scale is used to assess overall severity on a 7-point scale. Each of the CGI-Tics-Severity response categories was assigned a numerical score as follows: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patient.

4. Change From Randomization Baseline to the Week 36 Visit in the CGI-Tics-Severity Score [Randomization Baseline (Week 8, 10 or 12); Week 36]

   The CGI-Tics-Severity scale is used to assess overall severity on a 7-point scale. Each of the CGI-Tics-Severity response categories was assigned a numerical score as follows: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patient.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Have a clinical diagnosis of Tourette Syndrome (TS)

2. Have at least moderate tic severity

3. Have TS symptoms that impair school, occupational, and/or social function

4. If using maintenance medication(s) for TS or TS spectrum diagnoses (e.g. obsessive-compulsive disorder [OCD], Attention-Deficit Hyperactivity Disorder [ADHD]), be on stable doses

5. Be in good general health

6. Adolescent subjects (12 to 17 years of age) must have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids and a negative alcohol screen

7. Subjects of childbearing potential who do not practice total abstinence 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

Exclusion Criteria:

1. Have an active, clinically significant unstable medical condition within 1 month prior to screening

2. Have a known history of long QT syndrome or cardiac arrhythmia

3. Have a known history of neuroleptic malignant syndrome

4. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed)

5. Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors

6. Have a blood loss ≥250 mL or donated blood within 30 days prior to screening

7. Have a known history of substance dependence, substance (drug) or alcohol abuse

8. Have a significant risk of suicidal or violent behavior

9. Have initiated Comprehensive Behavioral Intervention for Tics (CBIT) during the screening period or at baseline or plan to initiate CBIT during the study

10. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study

11. Have previously participated in an NBI-98854 clinical study, except for NBI-98854-1403 or NBI-98854-1501.

12. Have HIV, hepatitis B, or hepatitis C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neuricrine Clinical Site	Sun City	Arizona	United States	85351
2	Neurocrine Clinical Site	Little Rock	Arkansas	United States	72205
3	Neurocrine Clinical Site	Rogers	Arkansas	United States	72758
4	Neurocrine Clinical Site	Anaheim	California	United States	92805
5	Neurocrine Clinical Site	Fullerton	California	United States	92835
6	Neurocrine Clinical Site	San Diego	California	United States	92108
7	Neurocrine Clinical Site	Santa Ana	California	United States	92705
8	Neurocrine Clinical Site	Pueblo	Colorado	United States	81003
9	Neurocrine Clinical Site	Stamford	Connecticut	United States	06905
10	Neurocrine Clinical Site	Washington	District of Columbia	United States	22207
11	Neurocrine Clinical Site	Gulf Breeze	Florida	United States	32561
12	Neurocrine Clinical Site	Hialeah	Florida	United States	33012
13	Neurocrine Clinical Site	Miami	Florida	United States	33125
14	Neurocrine Clinical Site	Miami	Florida	United States	33136
15	Neurocrine Clinical Site	North Miami	Florida	United States	33161
16	Neurocrine Clinical Site	Orlando	Florida	United States	32803
17	Neurocrine Clinical Site	Palmetto Bay	Florida	United States	33157
18	Neurocrine Clinical Site	Saint Petersburg	Florida	United States	33701
19	Neurocrine Clinical Site	Spring Hill	Florida	United States	34609
20	Neurocrine Clinical Site	Tallahassee	Florida	United States	32308
21	Neurocrine Clinical Site	Atlanta	Georgia	United States	30338
22	Neurocrine Clinical Site	Fayetteville	Georgia	United States	30214
23	Neurocrine Clinical Site	Savannah	Georgia	United States	31406
24	Neurocrine Clinical Site	Chicago	Illinois	United States	60634
25	Neurocrine Clinical Site	South Bend	Indiana	United States	46617
26	Neurocrine Clinical Site	Boston	Massachusetts	United States	02114
27	Neurocrine Clinical Site	Ann Arbor	Michigan	United States	48015
28	Neurocrine Clinical Site	Bloomfield Hills	Michigan	United States	48302
29	Neurocrine Clinical Site	West Bloomfield	Michigan	United States	48322
30	Neurocrine Clinical Site	Lincoln	Nebraska	United States	68526
31	Neurocrine Clinical Site	Nashua	New Hampshire	United States	03060
32	Neurocrine Clinical Site	Cherry Hill	New Jersey	United States	08002
33	Neurocrine Clinical Site	Mount Arlington	New Jersey	United States	07856
34	Neurocrine Clinical Site	New York	New York	United States	10036
35	Neurocrine Clinical Site	S. Setauket	New York	United States	11720
36	Neurocrine Clinical Site	Charlotte	North Carolina	United States	29141
37	Neurocrine Clinical Site	Mason	Ohio	United States	45040
38	Neurocrine Clinical Site	Oklahoma City	Oklahoma	United States	73112
39	Neurocrine Clinical Site	Dallas	Texas	United States	75243
40	Neurocrine Clinical Site	DeSoto	Texas	United States	75115
41	Neurocrine Clinical Site	Houston	Texas	United States	77030
42	Neurocrine Clinical Site	Houston	Texas	United States	77058
43	Neurocrine Clinical Site	Irving	Texas	United States	75062
44	Neurocrine Clinical Site	San Antonio	Texas	United States	78249
45	Neurocrine Clinical Site	Charlottesville	Virginia	United States	22903
46	Neurocrine Clinical Site	Bothell	Washington	United States	98011
47	Neurocrine Clinical Site	Everett	Washington	United States	98201
48	Neurocrine Clinical Site	Spokane	Washington	United States	99202
49	Neurocrine Clinical Site	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• Neurocrine Biosciences

Investigators

• Study Director: Clinical Development Lead, Neurocrine Biosciences

Study Documents (Full-Text)

• Study Protocol - Dec 3, 2018
• Statistical Analysis Plan - Aug 2, 2019

More Information

Publications

None provided.

• Responsible Party: Neurocrine Biosciences
• ClinicalTrials.gov Identifier: NCT03530293
• Other Study ID Numbers: NBI-98854-TS2005
• First Posted: May 21, 2018
• Last Update Posted: May 17, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tourette Syndrome; Syndrome

Study Results

Participant Flow

Recruitment Details	Up to 180 male and female pediatric subjects between 6 and 17 years of age (inclusive) with a DSM-IV or -V diagnosis of TS were planned to be enrolled. A total of 81 subjects were enrolled. The first and last participants were enrolled on April 17 2018 and May 7 2019, respectively.
Pre-assignment Detail	At the end of Weeks 8, 10, or 12, treatment responders (sufficient control of tic behaviors based on investigator assessment) were randomized in a 1:1 ratio to placebo or valbenazine. Randomization was stratified based on the subject's weight group at baseline (<50 kg versus ≥50 kg). The visit week when subjects were randomized was blinded. At Week 12 all nonresponders were discontinued.

Arm/Group Title	Pre-randomization Valbenazine	Randomized Placebo	Randomized Valbenazine
Arm/Group Description	Participants received valbenazine once daily for up to 12 weeks, depending on if and when randomization occurred. The starting dose was 20 mg for participants <50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for participants <50 kg and 80 mg for participants ≥50 kg to achieve an optimal dose of valbenazine for each participant.	Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization.	Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization.
Period Title: Pre-randomization
STARTED	81	0	0
Safety Analysis Set	80	0	0
COMPLETED	57	0	0
NOT COMPLETED	24	0	0
Period Title: Pre-randomization
STARTED	0	26	26
COMPLETED	0	9	9
NOT COMPLETED	0	17	17

Baseline Characteristics

Arm/Group Title	Randomized Placebo	Randomized Valbenazine	Total
Arm/Group Description	Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization.	Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization.	Total of all reporting groups
Overall Participants	26	26	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.7 (2.7)	12.8 (3.1)	12.8 (2.9)
Sex: Female, Male (Count of Participants)
Female	5 19.2%	2 7.7%	7 13.5%
Male	21 80.8%	24 92.3%	45 86.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 30.8%	6 23.1%	14 26.9%
Not Hispanic or Latino	18 69.2%	20 76.9%	38 73.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 3.8%	0 0%	1 1.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 7.7%	0 0%	2 3.8%
White	22 84.6%	24 92.3%	46 88.5%
More than one race	0 0%	1 3.8%	1 1.9%
Unknown or Not Reported	1 3.8%	1 3.8%	2 3.8%

Outcome Measures

1. Primary Outcome

Title	Time to Loss of Treatment Response
Description	Loss of treatment response during the withdrawal period was defined as: 2 consecutive visits with 1) an increase in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) of greater than 35% or 7 points from the randomized withdrawal period baseline and 2) an increase in CGI-Tics-Severity score of ≥2 points from the randomized withdrawal period baseline; or discontinuation due to lack of efficacy or a treatment-emergent adverse event (TEAE) of worsening of tics. Median (lower and upper quartiles) Kaplan-Meier estimates for the time to loss of treatment response were not able to be calculated because of the low incidence of loss of treatment response events.
Time Frame	Randomization (Week 8, 10 or 12) through Week 36

Outcome Measure Data

Analysis Population Description

The full analysis set includes all subjects who were randomized to a treatment group and had at least one post-randomization visit where loss of treatment response was able to be assessed.

Arm/Group Title	Randomized Placebo	Randomized Valbenazine
Arm/Group Description	Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Placebo oral capsule: non-active dosage form	Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Valbenazine: vesicular monoamine transporter 2 (VMAT2) inhibitor
Measure Participants	26	26
Median (95% Confidence Interval) [Days]	NA	NA

2. Secondary Outcome

Title	Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the YGTSS TTS
Description	The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity. Least-squares mean were estimated using a mixed-effects model for repeated measures.
Time Frame	Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization

Outcome Measure Data

Analysis Population Description

The full analysis set includes all subjects who were randomized to a treatment group and had at least one post-randomization visit where loss of treatment response was able to be assessed. Participants who do not have a TTS value at a scheduled or mapped early termination visit after randomization are not included in the analysis.

Arm/Group Title	Randomized Placebo	Randomized Valbenazine
Arm/Group Description	Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Placebo oral capsule: non-active dosage form	Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Valbenazine: vesicular monoamine transporter 2 (VMAT2) inhibitor
Measure Participants	26	25
Least Squares Mean (Standard Error) [units on a scale]	3.8 (1.6)	-1.0 (1.7)

3. Secondary Outcome

Title	Change From Randomization Baseline to the Week 36 Visit in the YGTSS TTS
Description	The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity.
Time Frame	Randomization Baseline (Week 8, 10 or 12); Week 36

Outcome Measure Data

Analysis Population Description

The full analysis set includes all subjects who were randomized to a treatment group and had at least one post-randomization visit where loss of treatment response was able to be assessed.

Arm/Group Title	Randomized Placebo	Randomized Valbenazine
Arm/Group Description	Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Placebo oral capsule: non-active dosage form	Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Valbenazine: vesicular monoamine transporter 2 (VMAT2) inhibitor
Measure Participants	9	9
Mean (Standard Deviation) [units on a scale]	0.6 (12.06)	0.1 (8.21)

4. Secondary Outcome

Title	Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the CGI-Tics-Severity Score
Description	The CGI-Tics-Severity scale is used to assess overall severity on a 7-point scale. Each of the CGI-Tics-Severity response categories was assigned a numerical score as follows: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patient.
Time Frame	Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization

Outcome Measure Data

Analysis Population Description

The full analysis set includes all subjects who were randomized to a treatment group and had at least one post-randomization visit where loss of treatment response was able to be assessed. Participants who do not have a CGI-Tics-Severity value at a scheduled or mapped early termination visit after randomization are not included in the analysis.

Arm/Group Title	Randomized Placebo	Randomized Valbenazine
Arm/Group Description	Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Placebo oral capsule: non-active dosage form	Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Valbenazine: vesicular monoamine transporter 2 (VMAT2) inhibitor
Measure Participants	22	19
Least Squares Mean (Standard Error) [units on a scale]	0.7 (0.2)	-0.1 (0.2)

5. Secondary Outcome

Title	Change From Randomization Baseline to the Week 36 Visit in the CGI-Tics-Severity Score
Description	The CGI-Tics-Severity scale is used to assess overall severity on a 7-point scale. Each of the CGI-Tics-Severity response categories was assigned a numerical score as follows: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patient.
Time Frame	Randomization Baseline (Week 8, 10 or 12); Week 36

Outcome Measure Data

Analysis Population Description

The full analysis set includes all subjects who were randomized to a treatment group and hac at least one post-randomization visit where loss of treatment response was able to be assessed.

Arm/Group Title	Randomized Placebo	Randomized Valbenazine
Arm/Group Description	Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Placebo oral capsule: non-active dosage form	Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Valbenazine: vesicular monoamine transporter 2 (VMAT2) inhibitor
Measure Participants	9	9
Mean (Standard Deviation) [units on a scale]	0.1 (0.78)	0.2 (1.30)

Adverse Events

Time Frame	Pre-randomization valbenazine group: from baseline up to randomization (Week 8, 10 or 12) or end of participation in subjects who did not randomize, up to 16 weeks. Randomized placebo and valbenazine groups: from randomization (Week 8, 10 or 12) up to Week 40
Arm/Group Title	Pre-randomization Valbenazine		Randomized Placebo		Randomized Valbenazine
Arm/Group Description	Participants received valbenazine once daily for up to 12 weeks, depending on if and when randomization occurs. The starting dose was 20 mg for participants <50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects <50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant. Valbenazine: vesicular monoamine transporter 2 (VMAT2) inhibitor		Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Placebo oral capsule: non-active dosage form		Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. Valbenazine: vesicular monoamine transporter 2 (VMAT2) inhibitor
All Cause Mortality
	Pre-randomization Valbenazine		Randomized Placebo		Randomized Valbenazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/26 (0%)		0/26 (0%)
Serious Adverse Events
	Pre-randomization Valbenazine		Randomized Placebo		Randomized Valbenazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/80 (1.3%)		2/26 (7.7%)		2/26 (7.7%)
Congenital, familial and genetic disorders
Tourette's disorder	0/80 (0%)		1/26 (3.8%)		0/26 (0%)
Infections and infestations
Enterovirus infection	1/80 (1.3%)		0/26 (0%)		0/26 (0%)
Nervous system disorders
Akathisia	0/80 (0%)		0/26 (0%)		1/26 (3.8%)
Psychiatric disorders
Tic	0/80 (0%)		0/26 (0%)		1/26 (3.8%)
Obsessive-compulsive disorder	0/80 (0%)		1/26 (3.8%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Pre-randomization Valbenazine		Randomized Placebo		Randomized Valbenazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/80 (51.3%)		12/26 (46.2%)		14/26 (53.8%)
Gastrointestinal disorders
Nausea	4/80 (5%)		1/26 (3.8%)		4/26 (15.4%)
Vomiting	4/80 (5%)		0/26 (0%)		3/26 (11.5%)
General disorders
Fatigue	10/80 (12.5%)		1/26 (3.8%)		0/26 (0%)
Irritability	6/80 (7.5%)		4/26 (15.4%)		4/26 (15.4%)
Infections and infestations
Gastroenteritis viral	0/80 (0%)		2/26 (7.7%)		1/26 (3.8%)
Upper respiratory tract infection	0/80 (0%)		1/26 (3.8%)		2/26 (7.7%)
Investigations
Weight increased	6/80 (7.5%)		0/26 (0%)		0/26 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/80 (2.5%)		2/26 (7.7%)		1/26 (3.8%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/80 (0%)		2/26 (7.7%)		0/26 (0%)
Myalgia	0/80 (0%)		1/26 (3.8%)		3/26 (11.5%)
Nervous system disorders
Headache	9/80 (11.3%)		3/26 (11.5%)		2/26 (7.7%)
Somnolence	20/80 (25%)		0/26 (0%)		1/26 (3.8%)
Psychiatric disorders
Aggression	1/80 (1.3%)		2/26 (7.7%)		0/26 (0%)
Anxiety	1/80 (1.3%)		4/26 (15.4%)		0/26 (0%)
Insomnia	5/80 (6.3%)		2/26 (7.7%)		0/26 (0%)
Suicidal ideation	1/80 (1.3%)		0/26 (0%)		2/26 (7.7%)
Tic	1/80 (1.3%)		0/26 (0%)		2/26 (7.7%)
Renal and urinary disorders
Haematuria	0/80 (0%)		0/26 (0%)		2/26 (7.7%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	7/80 (8.8%)		1/26 (3.8%)		1/26 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.