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

Tardive Dyskinesia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01733121
• Other study ID #: NBI-98854-1202
• Status: Completed
• Phase: Phase 2
• First received: November 20, 2012
• Last updated: November 20, 2014
• Start date: December 2012
• Est. completion date: December 2013

Study information

• Verified date: November 2014
• Source: Neurocrine Biosciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dyskinesias
• Tardive Dyskinesia

Intervention

Drug:
• NBI-98854
25 mg capsule
• NBI-98854
50 mg capsule
• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Neurocrine Biosciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory efficacy assessment of NBI-98854 administered once daily for the treatment of tardive dyskinesia (TD) symptoms	Patient Global Impression of Change (PGIC) questionnaire.	Week 6	No
Other	Exploratory efficacy assessment of NBI-98854 administered once daily for the treatment of tardive dyskinesia (TD) symptoms	Tardive Dyskinesia Ratings Scale (TDRS)	Baseline; Weeks 2 and 6	No
Primary	Severity of tardive dyskinesia (TD) symptoms assessed by Abnormal Involuntary Movements Scale (AIMS)		Baseline	No
Primary	Severity of TD symptoms assessed by AIMS	Change from Baseline, Proportion of responders based on reduction from baseline	Week 2	No
Primary	Severity of TD symptoms assessed by AIMS	Change from Baseline, Proportion of responders based on reduction from baseline	Week 4	No
Primary	Severity of TD symptoms assessed by AIMS	Change from Baseline, Proportion of responders based on reduction from baseline	Week 6	No
Secondary	Clinical global impression - global improvement of TD (CGI-TD)	Clinician's perspective of the participant's overall improvement of TD symptoms over time	Weeks 2 and 6	No
Secondary	Number of Participants with Adverse Events following dosing with NBI-98854	Proportion of subjects reporting adverse events	Up to 14 weeks	Yes
Secondary	Evaluation of plasma concentrations of NBI-98854 and metabolites following repeated daily doses of NBI-98854	Plasma samples will be collected and analyzed to evaluate drug and metabolite plasma concentrations.	Weeks 2 and 6	No