Tardive DyskinesiaPhase 2NCT01733121
NBI-98854 Dose Titration Study for the Treatment of Tardive Dyskinesia
A Phase 2 study testing NBI-98854 in people with Tardive Dyskinesia, run by Neurocrine Biosciences at 22 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Tardive Dyskinesia
- What is being tested?
- NBI-98854
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 22 sitesin 2 countries
- Study dates
- Dec 2012to Dec 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
22 sites in 2 countries.
22 sites in 2 countries
United States21 sites
Study site
Baltimore, Maryland, 21287
Study site
Beachwood, Ohio, 44122
Study site
Bedford, Texas, 76021
Study site
Boca Raton, Florida, 33486
Study site
Chicago, Illinois, 60640
Study site
Conshohocken, Pennsylvania, 19428
Study site
Costa Mesa, California, 92626
Study site
DeSoto, Texas, 75115
Study site
Englewood, Colorado, 80113
Study site
Farmington Hills, Michigan, 48334
Study site
Fountain Valley, California, 92708
Study site
Hialeah, Florida, 33012
Study site
Houston, Texas, 77008
Study site
Houston, Texas, 77030
Study site
Irving, Texas, 75062
Study site
Miami, Florida, 33125
Study site
Middleburg Heights, Ohio, 44130
Study site
Oceanside, California, 92056
Study site
Phoenixville, Pennsylvania, 19460
Study site
Richland, Washington, 99352
Study site
San Antonio, Texas, 78229
About this study
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
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.
Read the 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
- Conditions
- Tardive Dyskinesia
- Being tested
- NBI-98854, Placebo
- Medical subject headings
- Tardive Dyskinesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NBI-98854Drug
25 mg capsule
NBI-98854Drug
50 mg capsule
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| NBI-98854 | Experimental | 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. Receives: Drug: NBI-98854 |
| Placebo | Placebo comparator | Capsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at 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.
Measured: Baseline and Week 6
Secondary outcomes (2)
Clinical Global Impression - Global Improvement of TD (CGI-TD) at 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).
Measured: Week 6
AIMS Dyskinesia Total Score Change From Baseline at 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.
Measured: Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2012 (estimated)
- Study startDec 2012
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Tardive DyskinesiaStudies of the same condition, open and under way.
- More trials run by Neurocrine BiosciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurocrine Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chris O'Brien, MD, Study director, Neurocrine Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01733121
- Sponsor's protocol ID
- NBI-98854-1202
- Status last verified
- Jul 2017
- First submitted
- 20 Nov 2012
- Last updated
- 10 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31617235Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites. J Pharmacol Exp Ther. 2017 Jun;361(3):454-461. doi: 10.1124/jpet.116.239160. Epub 2017 Apr 12.
PubMed 28404690
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01733121
- Acronym / sponsor ID
- NBI-98854-1202
- Conditions
- Tardive Dyskinesia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Neurocrine BiosciencesIndustry (pharma, biotech, devices)
- Study start
- Dec 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 26 Nov 2012 (estimated)
- Results
- Posted 10 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NBI-98854 | Experimental | Drug: NBI-98854Dose 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. |
| Placebo | Placebo comparator | Drug: PlaceboCapsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NBI-9885425 mg capsule | Drug | NBI-98854 |
| NBI-9885450 mg capsule | Drug | NBI-98854 |
| Placebo | Drug | Placebo |
Primary outcome
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.
2 secondary outcomes
Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 6
Time frame: Week 6
AIMS Dyskinesia Total Score Change From Baseline at Week 6
Time frame: Week 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31617235Sajatovic 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.
- Derived from this study: PubMed 28404690Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites. J Pharmacol Exp Ther. 2017 Jun;361(3):454-461. doi: 10.1124/jpet.116.239160. Epub 2017 Apr 12.
Related trials for Tardive Dyskinesia
RecruitingPhase 4
A Study to Evaluate the Effectiveness of Valbenazine in Adult Participants With Tardive Dyskinesia (TD) Who Remain Symptomatic While Receiving or After Stopping a Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor
Schizophrenia, Schizoaffective Disorder
Not yet recruitingObservational study
A Computer-Assisted Tool for Objective Assessment of Extrapyramidal Symptoms
Extrapyramidal Symptoms, Drug-induced Parkinsonism
RecruitingPhase 4
Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
Tardive Dyskinesia, Intellectual Disability
RecruitingPhase 2
Efficacy, Safety, and Tolerability of NBI-1065890 Versus Placebo in Adults With Tardive Dyskinesia
Tardive Dyskinesia
Recruiting
Single-Center, Double-Blind, Randomized, Placebo-Controlled Study on Efficacy and Safety of rTMS (With Precise Localization) in Relieving Motor Symptoms of TD
Tardive Dyskinesia, Repetitive Transcranial Magnetic Stimulation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris O'Brien, MD study director
Neurocrine Biosciences
22 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NBI-98854 in people with Tardive Dyskinesia, run by Neurocrine Biosciences at 22 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6 (time frame: Baseline and Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01733121, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2017.