NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder (KINECT Study)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Neurocrine Biosciences
ClinicalTrials.gov Identifier:
NCT01688037
First received: September 11, 2012
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to evaluate the efficacy, safety, and tolerability of two doses (50 and 100 mg) of NBI-98854 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 Study to Assess the Efficacy and Safety of NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder

Resource links provided by NLM:


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 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 22 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 (50 mg and 100 mg) of NBI-98854 [ Time Frame: Weeks 2, 6, 8, 12, 14, and 16 ] [ 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 50 mg or 100 mg doses of NBI-98854 administered once daily for the treatment of tardive dyskinesia (TD) symptoms [ Time Frame: Weeks 2, 6, 8, 12, and 16 ] [ Designated as safety issue: No ]
    Patient Global Impression of Change (PGIC) questionnaire.

  • Exploratory efficacy assessment of 50 mg or 100 mg doses of NBI-98854 administered once daily for the treatment of tardive dyskinesia (TD) symptoms [ Time Frame: Baseline; Weeks 2, 6, 12, and 16 ] [ Designated as safety issue: No ]
    Tardive Dyskinesia Ratings Scale (TDRS)


Enrollment: 109
Study Start Date: September 2012
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NBI-98854 50 mg
NBI-98854 50 mg administered as two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for 6 weeks.
Drug: NBI-98854
25 mg capsule
Experimental: NBI-98854 100 mg and 50 mg
NBI-98854 100 mg administered as two (2) 50 mg capsules taken every morning between 7:00am - 10:00am for 2 weeks. After 2 weeks, NBI-98854 50 mg administered by two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for remaining 4 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, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety, and tolerability of two doses (50 and 100 mg) of NBI-98854 administered once daily for up to 2 weeks. The study will also allow for an evaluation of the efficacy of NBI-98854 50 mg once daily for up to 6 weeks and the safety and tolerability of NBI 98854 50 mg once daily for up to 12 weeks.

The double-blind placebo-controlled treatment period the study has three arms:

  • NBI-98854 50 mg once daily for 6 weeks
  • NBI-98854 100 mg once daily for 2 weeks followed by 50 mg once daily for the remaining 4 weeks
  • placebo

At the end of the 6-week placebo-controlled double-blind treatment period, subjects will continue in the study for an additional 6-week open-label period where all subjects who have completed the double-blind treatment period will receive NBI-98854 50 mg once daily. Two and four weeks after the last dose of study drug, follow-up assessments will be performed.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a clinical diagnosis of schizophrenia or schizoaffective disorder and 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01688037

  Show 51 Study Locations
Sponsors and Collaborators
Neurocrine Biosciences
Investigators
Study Director: Chris O'Brien, MD Neurocrine Biosciences
  More Information

Additional Information:
No publications provided

Responsible Party: Neurocrine Biosciences
ClinicalTrials.gov Identifier: NCT01688037     History of Changes
Other Study ID Numbers: NBI-98854-1201
Study First Received: September 11, 2012
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Dyskinesias
Psychotic Disorders
Schizophrenia
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on April 23, 2014