NBI-98854 Dose Titration Study for the Treatment of Tardive Dyskinesia

NCT ID: NCT01733121

Last Updated: 2017-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2013-12-31

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

Conditions

Tardive Dyskinesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NBI-98854

Dose titration to determine a subject's optimal dose in the range of 25 to 75 mg NBI-98854. Dose titration is performed in increments of 25 mg. NBI-98854 administered as one (1) 25 mg capsule, two (2) 25 mg capsules, or one (1) 25 mg capsule and one (1) 50 mg capsule by mouth, taken every morning between 7:00am - 10:00am for 6 weeks.

Group Type: EXPERIMENTAL

NBI-98854

Intervention Type: DRUG

25 mg capsule

NBI-98854

Intervention Type: DRUG

50 mg capsule

Placebo

Capsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

NBI-98854

25 mg capsule

Intervention Type: DRUG

NBI-98854

50 mg capsule

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neurocrine Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chris O'Brien, MD

Role: STUDY_DIRECTOR

Neurocrine Biosciences

Locations

Costa Mesa, California, United States

Fountain Valley, California, United States

Oceanside, California, United States

Englewood, Colorado, United States

Boca Raton, Florida, United States

Hialeah, Florida, United States

Miami, Florida, United States

Chicago, Illinois, United States

Baltimore, Maryland, United States

Farmington Hills, Michigan, United States

Beachwood, Ohio, United States

Middleburg Heights, Ohio, United States

Conshohocken, Pennsylvania, United States

Phoenixville, Pennsylvania, United States

Bedford, Texas, United States

DeSoto, Texas, United States

Houston, Texas, United States

Houston, Texas, United States

Irving, Texas, United States

San Antonio, Texas, United States

Richland, Washington, United States

Caguas, , Puerto Rico

Countries

United States; Puerto Rico

References

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.

Reference Type: DERIVED

PMID: 31617235 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28404690 (View on PubMed)

Other Identifiers

NBI-98854-1202

Identifier Type: -

Identifier Source: org_study_id