Clinical trial NCT02274558: A Phase 3 Study of NBI-98854 for the Treatment of Tardive Dyskinesia
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel, Fixed-Dose Study to Assess the Efficacy, Safety, and Tolerability of NBI-98854 for the Treatment of Tardive Dyskinesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tardive Dyskinesia
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
First posted: 2014-10-24
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety, and tolerability of NBI-98854 administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.

Detailed description: This is a Phase 3, randomized, double-blind, placebo-controlled, parallel, fixed-dose study to evaluate the efficacy, safety, and tolerability of two doses of NBI-98854 (40 mg and 80 mg) compared to placebo, administered once daily. The study design includes a double-blind, placebo-controlled treatment period for 6 weeks and a double-blind NBI-98854 treatment period for an additional 42 weeks, for a total of 48 weeks of treatment. Final follow-up assessments will be conducted 4 weeks after the last dose of the study drug.

Eligibility criteria: Inclusion Criteria:

1. Subjects of childbearing potential 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.
2. Female subjects must not be pregnant.
3. Have one of the following clinical diagnoses for at least 3 months prior to screening: Schizophrenia or Schizoaffective Disorder, or Mood Disorder.
4. Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months prior to screening.
5. Have moderate or severe TD.
6. If using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder, be on stable doses.
7. Be in good general health.
8. Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
9. Have a negative drug screen for amphetamines,barbiturates, benzodiazepines, phencyclidine, cocaine, opiates, or cannabinoids

Exclusion Criteria:

1. Have an active, clinically significant unstable medical condition within 1 month prior to screening.
2. Have a known history of substance dependence, or substance (drug) or alcohol abuse
3. Have a significant risk of suicidal or violent behavior.
4. Have a known history of neuroleptic malignant syndrome.
5. Have a known history of long QT syndrome or cardiac tachy-arrhythmia.
6. Have a cancer diagnosis within 3 years of screening (some exceptions allowed)
7. Have received an investigational drug within 30 days prior to screening or plan to use an investigational drug (other than NBI-98854) during the study.
8. Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline.
9. Have an allergy, hypersensitivity, or intolerance to tetrabenazine.
10. Have had previous exposure with NBI-98854 or had previously participated in an NBI-98854 clinical study.
11. Are currently pregnant or breastfeeding.

Primary outcomes:
measure: Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
timeFrame: Baseline and Week 6
Secondary outcomes:
measure: Clinical Global Impression of Change - TD (CGI-TD) at Week 6
timeFrame: Week 6
measure: Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Responder Analysis at Week 6
timeFrame: Week 6
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Glendale
country: United States
state: California
city: Irvine
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: National City
country: United States
state: California
city: Norwalk
country: United States
state: California
city: Oakland
country: United States
state: California
city: Oceanside
country: United States
state: California
city: San Bernardino
country: United States
state: California
city: San Diego
country: United States
state: California
city: Torrance
country: United States
state: California
city: Bradenton
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Leesburg
country: United States
state: Florida
city: Maitland
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: North Miami
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Oak Brook
country: United States
state: Illinois
city: Shreveport
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Glen Burnie
country: United States
state: Maryland
city: Worcester
country: United States
state: Massachusetts
city: Flowood
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Amherst
country: United States
state: New York
city: Cedarhurst
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Pinehurst
country: United States
state: North Carolina
city: Dayton
country: United States
state: Ohio
city: Shaker Heights
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Conshohocken
country: United States
state: Pennsylvania
city: Norristown
country: United States
state: Pennsylvania
city: Phoenixville
country: United States
state: Pennsylvania
city: Scranton
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: DeSoto
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: Petersburg
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Vancouver
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Caguas
country: Puerto Rico
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Neurocrine Biosciences
name: Chris O'Brien, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sajatovic M, Alexopoulos GS, Burke J, Farahmand K, Siegert S. The effects of valbenazine on tardive dyskinesia in older and younger patients. Int J Geriatr Psychiatry. 2020 Jan;35(1):69-79. doi: 10.1002/gps.5218. Epub 2019 Oct 31.
citation: Correll CU, Cutler AJ, Kane JM, McEvoy JP, Liang GS, O'Brien CF. Characterizing Treatment Effects of Valbenazine for Tardive Dyskinesia: Additional Results From the KINECT 3 Study. J Clin Psychiatry. 2018 Dec 18;80(1):18m12278. doi: 10.4088/JCP.18m12278.
citation: Factor SA, Remington G, Comella CL, Correll CU, Burke J, Jimenez R, Liang GS, O'Brien CF. The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-Year KINECT 3 Extension Study. J Clin Psychiatry. 2017 Nov/Dec;78(9):1344-1350. doi: 10.4088/JCP.17m11777.
citation: Kane JM, Correll CU, Liang GS, Burke J, O'Brien CF. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder. Psychopharmacol Bull. 2017 Aug 1;47(3):69-76.
citation: Josiassen RC, Kane JM, Liang GS, Burke J, O'Brien CF. Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. Psychopharmacol Bull. 2017 Aug 1;47(3):61-68.
citation: Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites. J Pharmacol Exp Ther. 2017 Jun;361(3):454-461. doi: 10.1124/jpet.116.239160. Epub 2017 Apr 12.
citation: Hauser RA, Factor SA, Marder SR, Knesevich MA, Ramirez PM, Jimenez R, Burke J, Liang GS, O'Brien CF. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017 May 1;174(5):476-484. doi: 10.1176/appi.ajp.2017.16091037. Epub 2017 Mar 21.