A Phase 3 Study of NBI-98854 for the Treatment of Tardive Dyskinesia

Phase 3

Completed

• Conditions: Tardive Dyskinesia
• Interventions: Drug: NBI-98854; Drug: Placebo

• Registration Number: NCT02274558
• Lead Sponsor: Neurocrine Biosciences

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, and tolerability of NBI-98854 administered once daily for the treatment of Tardive Dyskinesia (TD) symptoms.

Detailed Description

This is a Phase 3, randomized, double-blind, placebo-controlled, parallel, fixed-dose study to evaluate the efficacy, safety, and tolerability of two doses of NBI-98854 (40 mg and 80 mg) compared to placebo, administered once daily. The study design includes a double-blind, placebo-controlled treatment period for 6 weeks and a double-blind NBI-98854 treatment period for an additional 42 weeks, for a total of 48 weeks of treatment. Final follow-up assessments will be conducted 4 weeks after the last dose of the study drug.

Study Timeline

• Study Start: 2014-10
• Study First Submitted: 2014-10-22
• Study First Submitted QC: 2014-10-22
• Study First Posted: 2014-10-24
• Primary Completion: 2015-09
• Study Completion: 2016-07
• Disposition First Submitted: 2016-10-12
• Disposition First Submitted QC: 2016-10-12
• Disposition First Posted: 2016-10-13
• Results First Submitted: 2017-05-11
• Status Verified: 2017-06
• Results First Submitted QC: 2017-06-09
• Last Update Submitted: 2017-06-09
• Results First Posted: 2017-07-11
• Last Update Posted: 2017-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 234

Inclusion Criteria

1. Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study.
2. Female subjects must not be pregnant.
3. Have one of the following clinical diagnoses for at least 3 months prior to screening: Schizophrenia or Schizoaffective Disorder, or Mood Disorder.
4. Have a clinical diagnosis of neuroleptic-induced TD for at least 3 months prior to screening.
5. Have moderate or severe TD.
6. If using maintenance medication(s) for schizophrenia or schizoaffective disorder, or mood disorder, be on stable doses.
7. Be in good general health.
8. Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
9. Have a negative drug screen for amphetamines,barbiturates, benzodiazepines, phencyclidine, cocaine, opiates, or cannabinoids

Exclusion Criteria

1. Have an active, clinically significant unstable medical condition within 1 month prior to screening.
2. Have a known history of substance dependence, or substance (drug) or alcohol abuse
3. Have a significant risk of suicidal or violent behavior.
4. Have a known history of neuroleptic malignant syndrome.
5. Have a known history of long QT syndrome or cardiac tachy-arrhythmia.
6. Have a cancer diagnosis within 3 years of screening (some exceptions allowed)
7. Have received an investigational drug within 30 days prior to screening or plan to use an investigational drug (other than NBI-98854) during the study.
8. Have a blood loss ≥550 mL or donated blood within 30 days prior to Baseline.
9. Have an allergy, hypersensitivity, or intolerance to tetrabenazine.
10. Have had previous exposure with NBI-98854 or had previously participated in an NBI-98854 clinical study.
11. Are currently pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NBI-98854 40 mg	NBI-98854	NBI-98854 administered as one (1) 40 mg capsule and one (1) placebo capsule, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
NBI-98854 40 mg	Placebo	NBI-98854 administered as one (1) 40 mg capsule and one (1) placebo capsule, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
NBI-98854 80 mg	NBI-98854	Subjects randomized to the NBI-98854 80 mg dose will receive NBI-98854 40 mg for the first week (administered as one (1) 40 mg capsule and one (1) placebo capsule), followed by NBI-98854 80 mg administered as two (2) 40 mg capsules, taken by mouth, every morning between 7:00am - 10:00am for 5 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
NBI-98854 80 mg	Placebo	Subjects randomized to the NBI-98854 80 mg dose will receive NBI-98854 40 mg for the first week (administered as one (1) 40 mg capsule and one (1) placebo capsule), followed by NBI-98854 80 mg administered as two (2) 40 mg capsules, taken by mouth, every morning between 7:00am - 10:00am for 5 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and continue with their current dose.
Placebo	NBI-98854	Placebo administered as two (2) placebo capsules, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and be randomized to either a 40 mg or 80 mg dose. Subjects re-randomized to receive NBI-98854 80 mg will receive 40 mg for the first week.
Placebo	Placebo	Placebo administered as two (2) placebo capsules, taken by mouth, every morning between 7:00am - 10:00am for 6 weeks. At the end of Week 6, subjects will enter a double-blind NBI-98854 treatment period and be randomized to either a 40 mg or 80 mg dose. Subjects re-randomized to receive NBI-98854 80 mg will receive 40 mg for the first week.

Primary Outcome Measures

Name	Time	Method
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6	Baseline and Week 6	Severity of TD symptoms assessed by AIMS dyskinesia total score (sum of items 1 through 7), as assessed by blinded central AIMS video raters. The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity.

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impression of Change - TD (CGI-TD) at Week 6	Week 6	Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse).
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Responder Analysis at Week 6	Week 6	Percentage of AIMS responders (subjects who had at least a 50 percent reduction in AIMS score from baseline)