Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome

• Sponsor: Neurocrine Biosciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02879578
• Collaborator: (none)
• Enrollment: 155
• Locations: 13
• Arms: 3
• Actual Duration (Months): 15.2
• Patients Per Site: 11.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Phase 2, open-label, fixed-dose titration study to evaluate the safety and tolerability of NBI-98854 administered once daily for a total of 24 weeks in children, adolescents, and adults with Tourette Syndrome (TS).

Condition or Disease	Intervention/Treatment	Phase
Tourette Syndrome	Drug: Valbenazine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Actual Study Start Date: Jul 25, 2016
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valbenazine (Children) Children (6 to 11 years of age) received valbenazine 10 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 20 mg or continue with the participant's current dose for the remainder of the treatment period.	Drug: Valbenazine; Other Names: NBI-98854
Experimental: Valbenazine (Adolescents) Adolescents (12 to 17 years of age) received valbenazine 20 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 40 mg or continue with the participant's current dose for the remainder of the treatment period.	Drug: Valbenazine; Other Names: NBI-98854
Experimental: Valbenazine (Adults) Adults (18 to 64 years of age) received valbenazine 40 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 80 mg or continue with the participant's current dose for the remainder of the treatment period.	Drug: Valbenazine; Other Names: NBI-98854

Outcome Measures

Primary Outcome Measures

1. Frequency of Treatment-emergent Adverse Events (TEAEs) [Baseline through Week 28]

   A TEAE is an adverse event not present prior to the initiation of study drug dosing, or is an already present event that worsens either in intensity or frequency following the initiation of study drug dosing.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have participated in and completed the NBI-98854-1501 (T-Force Green) or NBI-98854-1505 (T-Forward) Phase 2 study

• Have a clinical diagnosis of Tourette Syndrome (TS)

• 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

• 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

• Adolescent and adult subjects (12 to 64 years of age) must have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids and a negative alcohol screen. Subjects who are on stable doses of prescribed and supervised (not as needed) benzodiazepines, opiates, or psychostimulants (for subjects with comorbid ADHD) are allowed to participate in the study

• Be in good general health

Exclusion Criteria:

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

• Have a known history of long QT syndrome or cardiac arrhythmia

• Have a known history of neuroleptic malignant syndrome

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

• Have a blood loss ≥250 mL or donated blood within 56 days prior to screening (subjects 6 to 17 years of age); have a blood loss ≥550 mL or donated blood within 30 days prior to screening (subjects 18 to 64 years of age)

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

• Have a significant risk of suicidal or violent behavior

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Sun City	Arizona	United States
2		San Diego	California	United States
3		Loxahatchee Groves	Florida	United States
4		Saint Petersburg	Florida	United States
5		Tampa	Florida	United States
6		Naperville	Illinois	United States
7		Lincoln	Nebraska	United States
8		Summit	New Jersey	United States
9		New York	New York	United States
10		Norristown	Pennsylvania	United States
11		Nashville	Tennessee	United States
12		Fort Worth	Texas	United States
13		Spokane	Washington	United States

Sponsors and Collaborators

• Neurocrine Biosciences

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 1, 2017
• Statistical Analysis Plan - Mar 6, 2018

More Information

Publications

None provided.

• Responsible Party: Neurocrine Biosciences
• ClinicalTrials.gov Identifier: NCT02879578
• Other Study ID Numbers: NBI-98854-1601
• First Posted: Aug 25, 2016
• Last Update Posted: Apr 29, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Tourette Syndrome; Syndrome

Study Results

Participant Flow

Recruitment Details

The study enrolled male and female children (6 to 11 years of age), adolescents (12 to 17 years of age), and adults (18 to 64 years of age) from 34 centers in the United States. Participants must have a clinical diagnosis of Tourette Syndrome (TS) and must have previously completed participation in Study NB-98854-1501 or Study NBI-98854-1505. The first and last participant were enrolled on 25 July 2016 and 14 April 2017, respectively.

Arm/Group Title	Valbenazine (Children)	Valbenazine (Adolescents)	Valbenazine (Adults)
Arm/Group Description	Children (6 to 11 years of age) received valbenazine 10 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 20 mg or continue with the participant's current dose for the remainder of the treatment period.	Adolescents (12 to 17 years of age) received valbenazine 20 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 40 mg or continue with the participant's current dose for the remainder of the treatment period.	Adults (18 to 64 years of age) received valbenazine 40 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 80 mg or continue with the participant's current dose for the remainder of the treatment period.
Period Title: Overall Study
STARTED	33	41	81
Safety Analysis Set	33	40	79
COMPLETED	23	32	49
NOT COMPLETED	10	9	32

Baseline Characteristics

Arm/Group Title	Valbenazine (Children)	Valbenazine (Adolescents)	Valbenazine (Adults)	Total
Arm/Group Description	Children (6 to 11 years of age) received valbenazine 10 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 20 mg or continue with the participant's current dose for the remainder of the treatment period.	Adolescents (12 to 17 years of age) received valbenazine 20 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 40 mg or continue with the participant's current dose for the remainder of the treatment period.	Adults (18 to 64 years of age) received valbenazine 40 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 80 mg or continue with the participant's current dose for the remainder of the treatment period.	Total of all reporting groups
Overall Participants	33	40	79	152
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	9.5 (1.5)	13.7 (1.4)	34.6 (12.9)	23.6 (14.8)
Sex: Female, Male (Count of Participants)
Female	7 21.2%	8 20%	25 31.6%	40 26.3%
Male	26 78.8%	32 80%	54 68.4%	112 73.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 9.1%	6 15%	4 5.1%	13 8.6%
Not Hispanic or Latino	30 90.9%	34 85%	75 94.9%	139 91.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 1.3%	1 0.7%
Black or African American	3 9.1%	2 5%	1 1.3%	6 3.9%
White	30 90.9%	35 87.5%	76 96.2%	141 92.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Other	0 0%	1 2.5%	0 0%	1 0.7%
Multiple	0 0%	2 5%	1 1.3%	3 2%

Outcome Measures

1. Primary Outcome

Title	Frequency of Treatment-emergent Adverse Events (TEAEs)
Description	A TEAE is an adverse event not present prior to the initiation of study drug dosing, or is an already present event that worsens either in intensity or frequency following the initiation of study drug dosing.
Time Frame	Baseline through Week 28

Outcome Measure Data

Analysis Population Description

Safety analysis set, which includes all participants who received at least one dose of study drug and have any postbaseline data.

Arm/Group Title	Valbenazine (Children)	Valbenazine (Adolescents)	Valbenazine (Adults)
Arm/Group Description	Children (6 to 11 years of age) received valbenazine 10 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 20 mg or continue with the participant's current dose for the remainder of the treatment period.	Adolescents (12 to 17 years of age) received valbenazine 20 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 40 mg or continue with the participant's current dose for the remainder of the treatment period.	Adults (18 to 64 years of age) received valbenazine 40 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 80 mg or continue with the participant's current dose for the remainder of the treatment period.
Measure Participants	33	40	79
Count of Participants [Participants]	20 60.6%	29 72.5%	68 86.1%

Adverse Events

Time Frame	Up to 28 weeks
Arm/Group Title	Valbenazine (Children)		Valbenazine (Adolescents)		Valbenazine (Adults)
Arm/Group Description	Children (6 to 11 years of age) received valbenazine 10 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 20 mg or continue with the participant's current dose for the remainder of the treatment period.		Adolescents (12 to 17 years of age) received valbenazine 20 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 40 mg or continue with the participant's current dose for the remainder of the treatment period.		Adults (18 to 64 years of age) received valbenazine 40 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 80 mg or continue with the participant's current dose for the remainder of the treatment period.
All Cause Mortality
	Valbenazine (Children)		Valbenazine (Adolescents)		Valbenazine (Adults)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/40 (0%)		0/79 (0%)
Serious Adverse Events
	Valbenazine (Children)		Valbenazine (Adolescents)		Valbenazine (Adults)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/40 (0%)		2/79 (2.5%)
Nervous system disorders
Extrapyramidal disorder	0/33 (0%)		0/40 (0%)		1/79 (1.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/33 (0%)		0/40 (0%)		1/79 (1.3%)
Other (Not Including Serious) Adverse Events
	Valbenazine (Children)		Valbenazine (Adolescents)		Valbenazine (Adults)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/33 (57.6%)		22/40 (55%)		57/79 (72.2%)
Gastrointestinal disorders
Nausea	2/33 (6.1%)		1/40 (2.5%)		3/79 (3.8%)
Vomiting	3/33 (9.1%)		2/40 (5%)		1/79 (1.3%)
General disorders
Fatigue	5/33 (15.2%)		4/40 (10%)		13/79 (16.5%)
Irritability	4/33 (12.1%)		0/40 (0%)		2/79 (2.5%)
Pyrexia	2/33 (6.1%)		1/40 (2.5%)		1/79 (1.3%)
Infections and infestations
Pharyngitis streptococcal	2/33 (6.1%)		0/40 (0%)		1/79 (1.3%)
Sinusitis	1/33 (3%)		2/40 (5%)		5/79 (6.3%)
Upper respiratory tract infection	2/33 (6.1%)		2/40 (5%)		11/79 (13.9%)
Investigations
Alanine aminotransferase increased	2/33 (6.1%)		0/40 (0%)		0/79 (0%)
Aspartate aminotransferase increased	2/33 (6.1%)		0/40 (0%)		0/79 (0%)
Protein urine present	2/33 (6.1%)		0/40 (0%)		0/79 (0%)
Weight increased	2/33 (6.1%)		3/40 (7.5%)		3/79 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/33 (6.1%)		0/40 (0%)		1/79 (1.3%)
Nervous system disorders
Akathisia	0/33 (0%)		1/40 (2.5%)		5/79 (6.3%)
Headache	5/33 (15.2%)		5/40 (12.5%)		5/79 (6.3%)
Lethargy	2/33 (6.1%)		0/40 (0%)		1/79 (1.3%)
Sedation	3/33 (9.1%)		8/40 (20%)		12/79 (15.2%)
Somnolence	3/33 (9.1%)		8/40 (20%)		16/79 (20.3%)
Psychiatric disorders
Abnormal dreams	0/33 (0%)		0/40 (0%)		4/79 (5.1%)
Depression	1/33 (3%)		0/40 (0%)		7/79 (8.9%)
Insomnia	2/33 (6.1%)		5/40 (12.5%)		3/79 (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.