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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Neurocrine Biosciences
ClinicalTrials.gov Identifier:
NCT01733121
First received: November 20, 2012
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Tardive Dyskinesia
Drug: NBI-98854
Drug: Placebo
Phase 2

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

Further study details as provided by Neurocrine Biosciences:

Primary Outcome Measures:
  • Severity of tardive dyskinesia (TD) symptoms assessed by Abnormal Involuntary Movements Scale (AIMS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Severity of TD symptoms assessed by AIMS [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Change from Baseline, Proportion of responders based on reduction from baseline

  • Severity of TD symptoms assessed by AIMS [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Change from Baseline, Proportion of responders based on reduction from baseline

  • Severity of TD symptoms assessed by AIMS [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    Change from Baseline, Proportion of responders based on reduction from baseline


Secondary Outcome Measures:
  • Clinical global impression - global improvement of TD (CGI-TD) [ Time Frame: Weeks 2 and 6 ] [ Designated as safety issue: No ]
    Clinician's perspective of the participant's overall improvement of TD symptoms over time

  • Number of Participants with Adverse Events following dosing with NBI-98854 [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: Yes ]
    Proportion of subjects reporting adverse events

  • Evaluation of plasma concentrations of NBI-98854 and metabolites following repeated daily doses of NBI-98854 [ Time Frame: Weeks 2 and 6 ] [ Designated as safety issue: No ]
    Plasma samples will be collected and analyzed to evaluate drug and metabolite plasma concentrations.


Other Outcome Measures:
  • Exploratory efficacy assessment of NBI-98854 administered once daily for the treatment of tardive dyskinesia (TD) symptoms [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    Patient Global Impression of Change (PGIC) questionnaire.

  • Exploratory efficacy assessment of NBI-98854 administered once daily for the treatment of tardive dyskinesia (TD) symptoms [ Time Frame: Baseline; Weeks 2 and 6 ] [ Designated as safety issue: No ]
    Tardive Dyskinesia Ratings Scale (TDRS)


Enrollment: 102
Study Start Date: December 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: NBI-98854
25 mg capsule
Drug: NBI-98854
50 mg capsule
Placebo Comparator: Placebo
Capsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules.
Drug: Placebo

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

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01733121

Locations
United States, California
Costa Mesa, California, United States, 92626
Fountain Valley, California, United States, 92708
Oceanside, California, United States, 92056
United States, Colorado
Englewood, Colorado, United States, 80113
United States, Florida
Boca Raton, Florida, United States, 33486
Hialeah, Florida, United States, 33012
Miami, Florida, United States, 33125
United States, Illinois
Chicago, Illinois, United States, 60640
United States, Maryland
Baltimore, Maryland, United States, 21287
United States, Michigan
Farmington Hills, Michigan, United States, 48334
United States, Ohio
Beachwood, Ohio, United States, 44122
Middleburg Heights, Ohio, United States, 44130
United States, Pennsylvania
Conshohoken, Pennsylvania, United States, 19428
Phoenixville, Pennsylvania, United States, 19460
United States, Texas
Bedford, Texas, United States, 76021
DeSoto, Texas, United States, 75115
Houston, Texas, United States, 77008
Houston, Texas, United States, 77030
Irving, Texas, United States, 75062
San Antonio, Texas, United States, 78229
United States, Washington
Richland, Washington, United States, 99352
Puerto Rico
Caguas, Puerto Rico, 00725
Sponsors and Collaborators
Neurocrine Biosciences
Investigators
Study Director: Chris O'Brien, MD Neurocrine Biosciences
  More Information

No publications provided

Responsible Party: Neurocrine Biosciences
ClinicalTrials.gov Identifier: NCT01733121     History of Changes
Other Study ID Numbers: NBI-98854-1202
Study First Received: November 20, 2012
Last Updated: September 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Dyskinesias
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on November 20, 2014