Trial Outcomes & Findings for Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome (NCT NCT03530293)

Last Updated: 2022-05-17

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

81 participants

Primary outcome timeframe

Randomization (Week 8, 10 or 12) through Week 36

Results posted on

2022-05-17

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Pre-randomization Valbenazine 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.	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.	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.
Pre-randomization STARTED	81	0	0
Pre-randomization Safety Analysis Set	80	0	0
Pre-randomization COMPLETED	57	0	0
Pre-randomization NOT COMPLETED	24	0	0
Randomized Withdrawal Period / Follow-up STARTED	0	26	26
Randomized Withdrawal Period / Follow-up COMPLETED	0	9	9
Randomized Withdrawal Period / Follow-up NOT COMPLETED	0	17	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Pre-randomization Valbenazine 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.	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.	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.
Pre-randomization Adverse Event	12	0	0
Pre-randomization Protocol Violation	2	0	0
Pre-randomization Study Terminated by Sponsor	5	0	0
Pre-randomization Withdrawal by Subject	5	0	0
Randomized Withdrawal Period / Follow-up Adverse Event	0	2	4
Randomized Withdrawal Period / Follow-up Protocol Violation	0	0	1
Randomized Withdrawal Period / Follow-up Withdrawal by Subject	0	3	2
Randomized Withdrawal Period / Follow-up Lack of Efficacy	0	2	0
Randomized Withdrawal Period / Follow-up Study Terminated by Sponsor	0	10	10

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized Placebo n=26 Participants 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.	Randomized Valbenazine n=26 Participants 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 n=52 Participants Total of all reporting groups
Age, Continuous	12.7 years STANDARD_DEVIATION 2.7 • n=5 Participants	12.8 years STANDARD_DEVIATION 3.1 • n=7 Participants	12.8 years STANDARD_DEVIATION 2.9 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	24 Participants n=7 Participants	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	20 Participants n=7 Participants	38 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	1 Participants n=5 Participants	0 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	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	24 Participants n=7 Participants	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization (Week 8, 10 or 12) through Week 36

Outcome measures

Outcome measures
Measure	Randomized Placebo n=26 Participants 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	Randomized Valbenazine n=26 Participants 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
Time to Loss of Treatment Response	NA Days 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.	NA Days 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

Timeframe: Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Randomized Placebo n=26 Participants 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	Randomized Valbenazine n=25 Participants 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
Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the YGTSS TTS	3.8 units on a scale Standard Error 1.6	-1.0 units on a scale Standard Error 1.7

SECONDARY outcome

Timeframe: Randomization Baseline (Week 8, 10 or 12); Week 36

Outcome measures

Outcome measures
Measure	Randomized Placebo n=9 Participants 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	Randomized Valbenazine n=9 Participants 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
Change From Randomization Baseline to the Week 36 Visit in the YGTSS TTS	0.6 units on a scale Standard Deviation 12.06	0.1 units on a scale Standard Deviation 8.21

SECONDARY outcome

Timeframe: Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Randomized Placebo n=22 Participants 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	Randomized Valbenazine n=19 Participants 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
Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the CGI-Tics-Severity Score	0.7 units on a scale Standard Error 0.2	-0.1 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Randomization Baseline (Week 8, 10 or 12); Week 36

Population: 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.

Outcome measures

Outcome measures
Measure	Randomized Placebo n=9 Participants 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	Randomized Valbenazine n=9 Participants 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
Change From Randomization Baseline to the Week 36 Visit in the CGI-Tics-Severity Score	0.1 units on a scale Standard Deviation 0.78	0.2 units on a scale Standard Deviation 1.30

Adverse Events

Pre-randomization Valbenazine

Serious events: 1 serious events

Other events: 41 other events

Deaths: 0 deaths

Randomized Placebo

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Randomized Valbenazine

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pre-randomization Valbenazine n=80 participants at risk 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	Randomized Placebo n=26 participants at risk 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	Randomized Valbenazine n=26 participants at risk 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
Infections and infestations Enterovirus infection	1.2% 1/80 • 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	0.00% 0/26 • 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	0.00% 0/26 • 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
Nervous system disorders Akathisia	0.00% 0/80 • 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	0.00% 0/26 • 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	3.8% 1/26 • 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
Psychiatric disorders Tic	0.00% 0/80 • 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	0.00% 0/26 • 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	3.8% 1/26 • 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
Psychiatric disorders Obsessive-compulsive disorder	0.00% 0/80 • 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	3.8% 1/26 • 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	0.00% 0/26 • 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
Congenital, familial and genetic disorders Tourette's disorder	0.00% 0/80 • 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	3.8% 1/26 • 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	0.00% 0/26 • 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

Other adverse events

Additional Information

Neurocrine Medical Information

Neurocrine Biosciences

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

Measure	Pre-randomization Valbenazine n=80 participants at risk 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	Randomized Placebo n=26 participants at risk 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	Randomized Valbenazine n=26 participants at risk 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
Gastrointestinal disorders Nausea	5.0% 4/80 • 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	3.8% 1/26 • 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	15.4% 4/26 • 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
Gastrointestinal disorders Vomiting	5.0% 4/80 • 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	0.00% 0/26 • 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	11.5% 3/26 • 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
General disorders Fatigue	12.5% 10/80 • 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	3.8% 1/26 • 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	0.00% 0/26 • 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
General disorders Irritability	7.5% 6/80 • 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	15.4% 4/26 • 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	15.4% 4/26 • 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
Infections and infestations Gastroenteritis viral	0.00% 0/80 • 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	7.7% 2/26 • 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	3.8% 1/26 • 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
Infections and infestations Upper respiratory tract infection	0.00% 0/80 • 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	3.8% 1/26 • 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	7.7% 2/26 • 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
Investigations Weight increased	7.5% 6/80 • 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	0.00% 0/26 • 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	0.00% 0/26 • 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
Metabolism and nutrition disorders Decreased appetite	2.5% 2/80 • 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	7.7% 2/26 • 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	3.8% 1/26 • 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
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/80 • 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	7.7% 2/26 • 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	0.00% 0/26 • 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
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/80 • 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	3.8% 1/26 • 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	11.5% 3/26 • 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
Nervous system disorders Headache	11.2% 9/80 • 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	11.5% 3/26 • 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	7.7% 2/26 • 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
Nervous system disorders Somnolence	25.0% 20/80 • 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	0.00% 0/26 • 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	3.8% 1/26 • 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
Psychiatric disorders Aggression	1.2% 1/80 • 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	7.7% 2/26 • 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	0.00% 0/26 • 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
Psychiatric disorders Anxiety	1.2% 1/80 • 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	15.4% 4/26 • 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	0.00% 0/26 • 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
Psychiatric disorders Insomnia	6.2% 5/80 • 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	7.7% 2/26 • 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	0.00% 0/26 • 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
Psychiatric disorders Suicidal ideation	1.2% 1/80 • 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	0.00% 0/26 • 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	7.7% 2/26 • 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
Psychiatric disorders Tic	1.2% 1/80 • 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	0.00% 0/26 • 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	7.7% 2/26 • 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
Renal and urinary disorders Haematuria	0.00% 0/80 • 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	0.00% 0/26 • 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	7.7% 2/26 • 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
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.8% 7/80 • 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	3.8% 1/26 • 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	3.8% 1/26 • 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