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

• ClinicalTrials.gov Identifier: NCT01688037
• Recruitment Status: Completed
• First Posted: September 19, 2012
• Results First Posted: November 8, 2017
• Last Update Posted: November 8, 2017
• Sponsor: Neurocrine Biosciences
• Information provided by (Responsible Party): Neurocrine Biosciences

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Tardive Dyskinesia	Drug: NBI-98854; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: September 2012
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: October 2013

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6 [ Time Frame: Baseline and Week 6 ]
   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. The primary efficacy endpoint was the change from baseline in the AIMS dyskinesia total score at Week 6 between the pooled NBI-98854 50+100 mg group and placebo group analyzed using the ANCOVA model (LOCF, ITT analysis set).

Secondary Outcome Measures :

1. Clinical Global Impression - Global Improvement of TD (CGI-TD) [ Time Frame: 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). The ANOVA analysis of CGI-TD was conducted for the pooled NBI-98854 50+100 mg group and placebo group.
2. Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 2 [ Time Frame: Week 2 ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Arkansas

Little Rock, Arkansas, United States, 72211

United States, California

Anaheim, California, United States, 92804

Carson, California, United States, 90746

Colton, California, United States, 92324

Costa Mesa, California, United States, 92626

Downey, California, United States, 90241

Fountain Valley, California, United States, 92708

Glendale, California, United States, 91206

National City, California, United States, 91950

Oceanside, California, United States, 92056

Paramount, California, United States, 90723

San Bernardino, California, United States, 92408

San Diego, California, United States, 92103

San Diego, California, United States, 92108

San Diego, California, United States, 92121

San Diego, California, United States, 92123

Santa Ana, California, United States, 92705

United States, Florida

Fort Lauderdale, Florida, United States, 33334

Hialeah, Florida, United States, 33012

Lauderhill, Florida, United States, 33319

Melbourne, Florida, United States, 32901

Miami Springs, Florida, United States, 33166

North Miami, Florida, United States, 33161

Orange City, Florida, United States, 32763

United States, Georgia

Atlanta, Georgia, United States, 30342

United States, Illinois

Chicago, Illinois, United States, 60612

Chicago, Illinois, United States, 60640

Schaumburg, Illinois, United States, 60194

United States, Louisiana

New Orleans, Louisiana, United States, 70114

Shreveport, Louisiana, United States, 71104

United States, Maryland

Baltimore, Maryland, United States, 21285

Glen Burnie, Maryland, United States, 21061

United States, Missouri

Saint Louis, Missouri, United States, 63118

Saint Louis, Missouri, United States, 63141

United States, New Jersey

Toms River, New Jersey, United States, 08755

United States, New York

Albany, New York, United States, 12208

Brooklyn, New York, United States, 11203

Wards Island, New York, United States, 10035

United States, North Carolina

Hope Mills, North Carolina, United States, 28348

United States, Ohio

Beachwood, Ohio, United States, 44122

United States, Oklahoma

Oklahoma City, Oklahoma, United States, 73112

United States, Pennsylvania

Conshohocken, Pennsylvania, United States, 19428

United States, South Carolina

Charleston, South Carolina, United States, 29407

United States, Tennessee

Memphis, Tennessee, United States, 38119

United States, Texas

DeSoto, Texas, United States, 75115

Irving, Texas, United States, 75062

United States, Washington

Bothell, Washington, United States, 98011

Kirkland, Washington, United States, 98033

Spokane, Washington, United States, 99204

Puerto Rico

Caguas, Puerto Rico, 00725

San Juan, Puerto Rico, 00927

Sponsors and Collaborators

Neurocrine Biosciences

Investigators

• Study Director: Chris O'Brien, MD; Neurocrine Biosciences

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Josiassen RC, Kane JM, Liang GS, Burke J, O'Brien CF. Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder. Psychopharmacol Bull. 2017 Aug 1;47(3):61-68.

• Responsible Party: Neurocrine Biosciences
• ClinicalTrials.gov Identifier: NCT01688037
• Other Study ID Numbers: NBI-98854-1201
• First Posted: September 19, 2012
• Results First Posted: November 8, 2017
• Last Update Posted: November 8, 2017
• Last Verified: October 2017

Additional relevant MeSH terms:

Dyskinesias; Tardive Dyskinesia; Schizophrenia; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Dyskinesia, Drug-Induced; Tetrabenazine; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs