Clinical trial NCT01733121: NBI-98854 Dose Titration Study for the Treatment of Tardive Dyskinesia
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Titration Study to Assess the Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Tardive Dyskinesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tardive Dyskinesia
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
First posted: 2012-11-26
Enrollment: 102
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 (titrated to a subject's optimal dose in the range of 25 to 75 mg) administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.

Detailed description: This is a Phase 2, randomized, double-blind, placebo-controlled, dose-titration study to evaluate the efficacy, safety, and tolerability of NBI-98854 (titrated to subject's optimal dose in the range of 25 to 75 mg) compared to placebo, administered once daily (q.d.) for a total of 6 weeks of treatment. Approximately 90 medically stable male and female subjects with one of the following clinical diagnoses will be enrolled: schizophrenia or schizoaffective disorder with neuroleptic-induced TD; mood disorder with neuroleptic-induced TD; or gastrointestinal disorder with metoclopramide-induced TD.

For subjects randomized to active treatment, the starting dose will be 25 mg NBI 98854, which may be escalated in increments of 25 mg every 2 weeks to a maximum of 75 mg to achieve an optimal dose of NBI-98854 for each subject

Eligibility criteria: Inclusion Criteria:

* Have one of the following clinical diagnoses for at least 3 months prior to screening a) schizophrenia or schizoaffective disorder; b) mood disorder; or c) gastrointestinal disorder (e.g., gastroparesis, gastroesophageal reflux disease)
* Have a clinical diagnosis of neuroleptic-induced tardive dyskinesia for at least 3 months prior to screening.
* Be receiving a stable dose of antipsychotic medication for a minimum of 30 days before study start. Subjects who are not using antipsychotic medication must have stable psychiatric status.
* Have the doses of concurrent medications and the conditions being treated be stable for a minimum of 30 days before study start and be expected to remain stable during the study.
* Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal birth control during the study.
* Female subjects must not be pregnant.
* Be in good general health and expected to complete the clinical study as designed.
* Have a body mass index (BMI) of 18 to 38 kg/m2 (both inclusive).
* Have a negative urine drug screen (negative for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids) at screening and study start, except for any subject receiving a stable dose of benzodiazepine.
* Have a negative alcohol breath test at screening and study start.

Exclusion Criteria:

* Have an active clinically significant unstable medical condition within 1 month (30 days) prior to screening.
* Have a history of substance dependence or substance (drug) or alcohol abuse within the 3 months before study start(nicotine and caffeine dependence are not exclusionary).
* Have a known history of neuroleptic malignant syndrome.
* Have a significant risk of suicidal or violent behavior.
* Receiving any excluded concomitant medication such as reserpine, metoclopramide, stimulants, or tetrabenazine.
* Receiving medication for the treatment of tardive dyskinesia.
* Have a positive human immunodeficiency virus antibody, (HIV-Ab), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody result at screening or have a history of positive result.
* Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study.
* Have an allergy, hypersensitivity, or intolerance to tetrabenazine.
* Have had previous exposure with NBI-98854.

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 - Global Improvement of TD (CGI-TD) at Week 6
timeFrame: Week 6
measure: AIMS Dyskinesia Total Score Change From Baseline at Week 6
timeFrame: Week 6
Other outcomes:
Locations:
city: Costa Mesa
country: United States
state: California
city: Fountain Valley
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Englewood
country: United States
state: Colorado
city: Boca Raton
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Farmington Hills
country: United States
state: Michigan
city: Beachwood
country: United States
state: Ohio
city: Middleburg Heights
country: United States
state: Ohio
city: Conshohocken
country: United States
state: Pennsylvania
city: Phoenixville
country: United States
state: Pennsylvania
city: Bedford
country: United States
state: Texas
city: DeSoto
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Richland
country: United States
state: Washington
city: Caguas
country: Puerto Rico
Study officials:
affiliation: Neurocrine Biosciences
name: Chris O'Brien, MD
role: STUDY_DIRECTOR
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: 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.