Rollover Study for Continuing Valbenazine (NBI-98854) Administration for the Treatment of Tardive Dyskinesia

• Sponsor: Neurocrine Biosciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02736955
• Collaborator: (none)
• Enrollment: 161
• Locations: 27
• Arm: 1
• Actual Duration (Months): 12.6
• Patients Per Site: 6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This Phase 3b, rollover study will provide participants who completed a Phase 3 valbenazine (NBI-98854) study open-label access to valbenazine (fixed doses administered once daily) for the treatment of adults with TD until valbenazine is anticipated to be available commercially or they complete 72 weeks of treatment. This study will allow enrollment of up to 150 medically stable male and female participants with TD who previously participated in and completed the NBI-98854-1304 (Kinect 3) or NBI-98854-1402 (Kinect 4) Phase 3 study.

Condition or Disease	Intervention/Treatment	Phase
Tardive Dyskinesia	Drug: Valbenazine	Phase 3

Detailed Description

This study was terminated after 60 weeks due to the commercial availability of valbenazine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 161 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Rollover Study for Continuing Valbenazine (NBI-98854) Administration for the Treatment of Tardive Dyskinesia
• Actual Study Start Date: Jun 13, 2016
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Jun 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valbenazine Fixed dose of valbenazine administered once daily for up to 72 weeks	Drug: Valbenazine; Other Names: NBI-98854

Outcome Measures

Primary Outcome Measures

1. Number of Participants Monitored for Long-term Safety of Valbenazine [60 weeks]

   Incidence of adverse events and monitoring of vital signs, clinical laboratory values, and electrocardiograms. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). Summaries of the incidence of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared.

Secondary Outcome Measures

1. Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale [Baseline and Weeks 12, 24, 36, 48, and 60]

   Clinician's perspective of the participant's overall severity of TD symptoms. The CGI-TD-Severity is based on a 7-point scale (range: 1= "Normal, not at all ill" to 7= "Among the most extremely ill patient"). A clinical response was defined as a CGI-TD-S score equal to "1" or "2."

2. Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ) [Baseline and Weeks 12, 24, 36, 48, and 60]

   Participant's perspective of his/her satisfaction with valbenazine treatment. The PSQ is based on a 5-point scale (range: 1=very satisfied to 5=very dissatisfied). A clinical response was defined as a PSQ score equal to "1" or "2."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have participated in and completed the NBI-98854-1304 (Kinect 3) or NBI-98854-1402 (Kinect 4) Phase 3 study.

• Participants of childbearing potential must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently throughout the study and until 30 days after the last dose of valbenazine.

• If using maintenance medication(s) for schizophrenia or schizoaffective disorder, mood disorder, or other conditions, be on stable doses.

• Be in general good health.

• Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.

Exclusion Criteria:

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

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

• Have a significant risk of suicidal or violent behavior.

• Have a known history of neuroleptic malignant syndrome.

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

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

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

• Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline.

• Have an allergy, hypersensitivity, or intolerance to tetrabenazine.

• Are currently pregnant or breastfeeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Anaheim	California	United States
2		National City	California	United States
3		Norwalk	California	United States
4		Oakland	California	United States
5		San Bernardino	California	United States
6		San Diego	California	United States
7		Torrance	California	United States
8		Hialeah	Florida	United States
9		North Miami	Florida	United States
10		Orlando	Florida	United States
11		Chicago	Illinois	United States
12		Shreveport	Louisiana	United States
13		Worcester	Massachusetts	United States
14		Cedarhurst	New York	United States
15		Dayton	Ohio	United States
16		Shaker Heights	Ohio	United States
17		Oklahoma City	Oklahoma	United States
18		Norristown	Pennsylvania	United States
19		Charleston	South Carolina	United States
20		Franklin	Tennessee	United States
21		Memphis	Tennessee	United States
22		DeSoto	Texas	United States
23		Fort Worth	Texas	United States
24		Irving	Texas	United States
25		Salt Lake City	Utah	United States
26		Petersburg	Virginia	United States
27		Spokane	Washington	United States

Sponsors and Collaborators

• Neurocrine Biosciences

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 19, 2017
• Statistical Analysis Plan - Oct 16, 2017

More Information

Publications

None provided.

• Responsible Party: Neurocrine Biosciences
• ClinicalTrials.gov Identifier: NCT02736955
• Other Study ID Numbers: NBI-98854-1506
• First Posted: Apr 13, 2016
• Last Update Posted: Dec 19, 2018
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Dyskinesias; Tardive Dyskinesia

Study Results

Participant Flow

Arm/Group Title	Valbenazine 40 mg	Valbenazine 80 mg	Valbenazine 40/80 mg
Arm/Group Description	Participants received 40 mg valbenazine oral capsule once daily for up to 60 weeks	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks, followed by 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily for up to 56 weeks	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks. Participants were then increased to 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily, and due to poor tolerance, were subsequently reduced back to one 40 mg valbenazine oral capsule once daily for the remainder of the study, up to 56 weeks
Period Title: Overall Study
STARTED	36	117	8
COMPLETED	29	103	6
NOT COMPLETED	7	14	2

Baseline Characteristics

Arm/Group Title	Valbenazine 40 mg	Valbenazine 80 mg	Valbenazine 40/80 mg	Total
Arm/Group Description	Participants received 40 mg valbenazine oral capsule once daily for up to 60 weeks.	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks, followed by 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily for up to 56 weeks	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks. Participants were then increased to 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily, and due to poor tolerance, were subsequently reduced back to one 40 mg valbenazine oral capsule once daily for the remainder of the study, up to 56 weeks	Total of all reporting groups
Overall Participants	35	117	8	160
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (8.9)	57.9 (8.8)	59.3 (9.0)	57.9 (8.8)
Sex: Female, Male (Count of Participants)
Female	22 62.9%	54 46.2%	3 37.5%	79 49.4%
Male	13 37.1%	63 53.8%	5 62.5%	81 50.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 11.4%	52 44.4%	1 12.5%	57 35.6%
Not Hispanic or Latino	31 88.6%	65 55.6%	7 87.5%	103 64.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 12.5%	1 0.6%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.9%	0 0%	1 0.6%
Black or African American	14 40%	30 25.6%	3 37.5%	47 29.4%
White	21 60%	86 73.5%	4 50%	111 69.4%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Body Mass Index (BMI) at Baseline (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.15 (5.52)	28.54 (5.48)	30.55 (5.29)	28.77 (5.46)
Primary Psychiatric Diagnosis (Count of Participants)
Schizophrenia/schizoaffective disorder	23 65.7%	75 64.1%	6 75%	104 65%
Mood disorder	12 34.3%	42 35.9%	2 25%	56 35%
Age at Diagnosis (years) [Mean (Standard Deviation) ]
Schizophrenia/Schizoaffective Disorder	27.1 (8.3)	28.7 (11.4)	25.3 (6.2)	28.2 (10.6)
Mood Disorder	36.0 (3.6)	33.9 (2.1)	46.0 (14.0)	34.7 (1.8)
Tardive Dyskinesia	48.3 (11.2)	48.4 (9.5)	43.8 (13.7)	48.0 (10.1)
Scales (units on a scale) [Mean (Standard Deviation) ]
BPRS Score	27.3 (6.3)	26.1 (5.6)	30.5 (9.2)	26.6 (6.0)
CGI-TD-Severity Score	3.9 (1.1)	3.9 (1.3)	4.3 (0.7)	3.9 (1.2)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Monitored for Long-term Safety of Valbenazine
Description	Incidence of adverse events and monitoring of vital signs, clinical laboratory values, and electrocardiograms. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). Summaries of the incidence of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared.
Time Frame	60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valbenazine 40 mg	Valbenazine 80 mg	Valbenazine 40/80 mg
Arm/Group Description	Participants received 40 mg valbenazine oral capsule once daily for up to 60 weeks.	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks, followed by 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily for up to 56 weeks	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks. Participants were then increased to 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily, and due to poor tolerance, were subsequently reduced back to one 40 mg valbenazine oral capsule once daily for the remainder of the study, up to 56 weeks
Measure Participants	35	117	8
Count of Participants [Participants]	35 100%	117 100%	8 100%

2. Secondary Outcome

Title	Number of Participants With Clinical Response as Assessed by the Clinical Global Impression of Tardive Dyskinesia - Severity (CGI-TD-Severity) Scale
Description	Clinician's perspective of the participant's overall severity of TD symptoms. The CGI-TD-Severity is based on a 7-point scale (range: 1= "Normal, not at all ill" to 7= "Among the most extremely ill patient"). A clinical response was defined as a CGI-TD-S score equal to "1" or "2."
Time Frame	Baseline and Weeks 12, 24, 36, 48, and 60

Outcome Measure Data

Analysis Population Description

Safety analysis set: includes all participants who were enrolled in the study and received study drug, with the following two exclusions: (a) participants who withdrew from the study and returned all previously dispensed study drug with all doses present, and (b) participants who had no post-baseline data collected.

Arm/Group Title	Valbenazine 40 mg	Valbenazine 80 mg	Valbenazine 40/80 mg
Arm/Group Description	Participants received 40 mg valbenazine oral capsule once daily for up to 60 weeks	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks, followed by 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily for up to 56 weeks	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks. Participants were then increased to 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily, and due to poor tolerance, were subsequently reduced back to one 40 mg valbenazine oral capsule once daily for the remainder of the study, up to 56 weeks
Measure Participants	35	117	8
Baseline	2 5.7%	21 17.9%	0 0%
Week 12	15 42.9%	56 47.9%	3 37.5%
Week 24	11 31.4%	56 47.9%	4 50%
Week 36	7 20%	44 37.6%	2 25%
Week 48	5 14.3%	29 24.8%	2 25%
Week 60	2 5.7%	2 1.7%

3. Secondary Outcome

Title	Number of Participants With Clinical Response as Assessed by the Patient Satisfaction Questionnaire (PSQ)
Description	Participant's perspective of his/her satisfaction with valbenazine treatment. The PSQ is based on a 5-point scale (range: 1=very satisfied to 5=very dissatisfied). A clinical response was defined as a PSQ score equal to "1" or "2."
Time Frame	Baseline and Weeks 12, 24, 36, 48, and 60

Outcome Measure Data

Analysis Population Description

Safety analysis set: includes all participants who were enrolled in the study and received study drug, with the following two exclusions: (a) participants who withdrew from the study and returned all previously dispensed study drug with all doses present, and (b) participants who had no post-baseline data collected.

Arm/Group Title	Valbenazine 40 mg	Valbenazine 80 mg	Valbenazine 40/80 mg
Arm/Group Description	Participants received 40 mg valbenazine oral capsule once daily for up to 60 weeks	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks, followed by 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily for up to 56 weeks	Participants received 40 mg valbenazine oral capsule once daily for 4 weeks. Participants were then increased to 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily, and due to poor tolerance, were subsequently reduced back to one 40 mg valbenazine oral capsule once daily for the remainder of the study, up to 56 weeks
Measure Participants	35	117	8
Baseline	35 100%	116 99.1%	7 87.5%
Week 12	30 85.7%	112 95.7%	6 75%
Week 24	23 65.7%	92 78.6%	6 75%
Week 36	17 48.6%	66 56.4%	5 62.5%
Week 48	12 34.3%	38 32.5%	5 62.5%
Week 60	2 5.7%	2 1.7%

Adverse Events

Time Frame	Up to 60 weeks
Arm/Group Title	Valbenazine 40 mg		Valbenazine 80 mg		Valbenazine 40/80 mg
Arm/Group Description	Participants received 40 mg valbenazine oral capsule once daily for up to 60 weeks.		Participants received 40 mg valbenazine oral capsule once daily for 4 weeks, followed by 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily for up to 56 weeks		Participants received 40 mg valbenazine oral capsule once daily for 4 weeks. Participants were then increased to 80 mg (provided as 2 x 40 mg valbenazine oral capsule) once daily, and due to poor tolerance, were subsequently reduced back to one 40 mg valbenazine oral capsule once daily for the remainder of the study, up to 56 weeks
All Cause Mortality
	Valbenazine 40 mg		Valbenazine 80 mg		Valbenazine 40/80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		3/117 (2.6%)		1/8 (12.5%)
Serious Adverse Events
	Valbenazine 40 mg		Valbenazine 80 mg		Valbenazine 40/80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/35 (8.6%)		11/117 (9.4%)		2/8 (25%)
Cardiac disorders
Atrial fibrillation	1/35 (2.9%)		0/117 (0%)		0/8 (0%)
Hypertensive heart disease	0/35 (0%)		0/117 (0%)		1/8 (12.5%)
Gastrointestinal disorders
Diarrhoea	1/35 (2.9%)		0/117 (0%)		0/8 (0%)
General disorders
Non-cardiac chest pain	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Infections and infestations
Gangrene	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Sepsis syndrome	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Pneumonia	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Injury, poisoning and procedural complications
Hip fracture	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Metabolism and nutrition disorders
Gout	0/35 (0%)		0/117 (0%)		1/8 (12.5%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Back pain	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Nervous system disorders
Coma	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Haemorrhagic stroke	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Psychiatric disorders
Aggression	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Psychotic disorder	1/35 (2.9%)		0/117 (0%)		0/8 (0%)
Depression	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Paranoia	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Mental status changes	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Renal and urinary disorders
Renal failure	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/35 (0%)		1/117 (0.9%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Valbenazine 40 mg		Valbenazine 80 mg		Valbenazine 40/80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/35 (17.1%)		23/117 (19.7%)		6/8 (75%)
Infections and infestations
Urinary tract infection	1/35 (2.9%)		6/117 (5.1%)		0/8 (0%)
Upper respiratory tract infection	1/35 (2.9%)		5/117 (4.3%)		0/8 (0%)
Injury, poisoning and procedural complications
Fall	1/35 (2.9%)		4/117 (3.4%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Back pain	2/35 (5.7%)		4/117 (3.4%)		0/8 (0%)
Nervous system disorders
Somnolence	1/35 (2.9%)		0/117 (0%)		5/8 (62.5%)
Headache	1/35 (2.9%)		4/117 (3.4%)		0/8 (0%)
Tremor	0/35 (0%)		3/117 (2.6%)		2/8 (25%)
Respiratory, thoracic and mediastinal disorders
Cough	2/35 (5.7%)		3/117 (2.6%)		1/8 (12.5%)

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.