Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication INGREZZA and INGREZZA SPRINKLE are indicated for the treatment of adults with: - tardive dyskinesia [see Clinical Studies ( 14.1 )] . - chorea associated with Huntington’s disease [see Clinical Studies ( 14.2 )] . INGREZZA and INGREZZA SPRINKLE are vesicular monoamine transporter 2 (VMAT2) inhibitors indicated for the treatment of adults with: - tardive dyskinesia. FDA label
Also known as Valbenazine, Ingrezza
NBI-98854 · 21 trials · 9 indications
The TMC is part of the motor assessment of the UHDRS and measures chorea in 7 different body parts including the face, oral-buccal-lingual region, trunk and each limb independently. The TMC score is the sum of the individual scores and ranges from 0 to 28. A decrease in TMC scores indicates improvement in chorea symptoms.
Incidence of adverse events and monitoring of vital signs, clinical laboratory values, and electrocardiograms. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). Summaries of the incidence of all treatment-emergent AEs, treatment-related AEs, SAEs, and AEs leading to study drug discontinuation were prepared.
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.
A clinician-administered scale assessing OCD severity that will be used at all 8 visits. Total scores range from 0-50. Higher scores indicate worse outcomes.
Massachusetts General Hospital Hairpulling Scale (MGH-HPS) scores range from 0-28 with 28 being the most severe. The lower the total score, the lower the severity level. This scale is given and measured once every 2 weeks for a total of 12 weeks.
The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity.
A TEAE is an adverse event not present prior to the initiation of study drug dosing, or is an already present event that worsens either in intensity or frequency following the initiation of study drug dosing.
The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity
The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity
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.
Abnormal Involuntary Movements Scale (AIMS) and Clinical Global Impression - Global Improvement of TD (CGI-TD) scale
| Arm | Type | Description |
|---|---|---|
| Valbenazine | EXPERIMENTAL | Capsule, administered orally once daily. |
| Placebo | PLACEBO_COMPARATOR | Placebo dosed for 14 weeks (double-blind treatment period) followed by open-label valbenazine treatment. Participants may opt to enter an open-label valbenazine treatment extension phase. |
| Vesicular monoamine transporter 2 (VMAT2) inhibitor | EXPERIMENTAL | Valbenazine once daily |
| Dose Group 1 | EXPERIMENTAL | Fixed dose of NBI-98854 administered once daily for 48 weeks |
| Dose Group 2 | EXPERIMENTAL | Fixed dose of NBI-98854 administered once daily up to 48 weeks |
| NBI-98854 40 mg | EXPERIMENTAL | 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 | EXPERIMENTAL | 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. |
| Valbenazine followed by placebo | OTHER | Following baseline measures, 50% of subjects will receive valbenazine (initially 40mg per day for 2 weeks and then 80mg per day for 4 weeks). This will be followed by a 2-week washout period and then 6 weeks of being assigned to the other agent. Participants will be assessed at baseline and every 2 weeks during the remainder of the study period. |
| Placebo followed by valbenazine | OTHER | Following baseline measures, 50% of subjects will receive inactive placebo for 6 weeks. This will be followed by a 2-week washout period and then 6 weeks of being assigned to the other agent (initially 40mg per day for 2 weeks and then 80mg per day for 4 weeks). Participants will be assessed at baseline and every 2 weeks during the remainder of the study period. |
| Valbenazine (Children) | EXPERIMENTAL | Children (6 to 11 years of age) received valbenazine 10 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 20 mg or continue with the participant's current dose for the remainder of the treatment period. |
| Valbenazine (Adolescents) | EXPERIMENTAL | Adolescents (12 to 17 years of age) received valbenazine 20 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 40 mg or continue with the participant's current dose for the remainder of the treatment period. |
| Valbenazine (Adults) | EXPERIMENTAL | Adults (18 to 64 years of age) received valbenazine 40 mg once daily for 4 weeks. At the end of Week 4, investigators could escalate the dose to 80 mg or continue with the participant's current dose for the remainder of the treatment period. |
| 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. |
| NBI-98854 50 mg | EXPERIMENTAL | NBI-98854 50 mg administered as two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for 6 weeks. |
| NBI-98854 100 mg and 50 mg | EXPERIMENTAL | 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. |
| NBI-98854 12.5 mg | EXPERIMENTAL | During the Cross-Over Study, subjects will be randomly assigned to receive one of the following treatment sequences: Sequence 1: Placebo once daily dose for Days 1-14 and 12.5 mg NBI-98854 once daily dose for Days 15-28. Sequence 2: 12.5 mg NBI-98854 once daily dose for Days 1-14 and placebo once daily dose for Days 15-28. |
| Adolescents Dose Group 1 | EXPERIMENTAL | Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. |
| Adolescents Dose Group 2 | EXPERIMENTAL | Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the adolescent dose group 1 have been reviewed to ensure there are no safety concerns and that maximum tolerated dose (MTD) has not been reached. |
| Adolescents Dose Group 3 | EXPERIMENTAL | Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the adolescent dose group 2 have been reviewed to ensure there are no safety concerns and that MTD has not been reached. |
| Children Dose Group 1 | EXPERIMENTAL | Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the adolescent dose group 1 have been reviewed to ensure there are no safety concerns and that MTD has not been reached. |
| Children Dose Group 2 | EXPERIMENTAL | Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the children dose group 1 have been reviewed to ensure there are no safety concerns and that MTD has not been reached. |
| Children Dose Group 3 | EXPERIMENTAL | Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the children dose group 2 have been reviewed to ensure there are no safety concerns and that MTD has not been reached. |
| Healthy Volunteers | EXPERIMENTAL | single dose of NBI-98854 50 mg capsule |
| Mild Hepatic Impairment | EXPERIMENTAL | single dose of NBI-98854 50 mg capsule |
| Moderate Hepatic Impairment | EXPERIMENTAL | single dose of NBI-98854 50 mg capsule |
| Severe Hepatic Impairment | EXPERIMENTAL | single dose of NBI-98854 50 mg capsule |
| Name | Type | Description |
|---|---|---|
| Valbenazine | DRUG | vesicular monoamine transporter 2 (VMAT2) inhibitor |
| Placebo | DRUG | Capsule, administered once daily orally or via gastrostomy/gastrojejunostomy tube |
| NBI-98854 | DRUG | - |
| Valbenazine Oral Capsule | DRUG | Participants randomized to active treatment will be given a starting dose of 40mg of valbenazine , which may be escalated to 80mg to achieve an optimal dose of the medication for each subject. |
| Placebo Oral capsule | OTHER | Participants randomized to placebo will be given a capsule that is the same shape and color as the active medication and will subject to the same dose escalation requirements as the other arm but will receive placebo during the treatment period. |
| NBI-98854 50 mg capsule | DRUG | - |
Key Inclusion Criteria: * Participated in Study NBI-98854-HD3006 and completing dosing through the Week 156 visit; or were actively participating, receiving study treatment, and completed an early termination visit Study NBI-98854-HD3006 at the time of the study closure at sites in Canada. * Partic...
NBI-98854 is an investigational small molecule developed by Neurocrine Biosciences, Inc. It has been studied in clinical trials for tardive dyskinesia and Tourette syndrome, and in a study of safety, tolerability, and pharmacokinetics in hepatically impaired subjects. It is not described as approved and remains in clinical development.
NBI-98854 has been studied for the treatment of tardive dyskinesia and Tourette syndrome. Trials have enrolled adults with tardive dyskinesia, adults with Tourette syndrome, and children and adolescents with Tourette syndrome. It has also been evaluated for safety, tolerability, and pharmacokinetics in hepatically impaired subjects.
NBI-98854 is developed by Neurocrine Biosciences, Inc., which trades under the ticker NBIX. The company is the sponsor of the clinical program studying the drug in tardive dyskinesia, Tourette syndrome, and hepatically impaired subjects.
NBI-98854 is an investigational drug that has been tested across Phase 1, Phase 2, and Phase 3 clinical trials. Six trials are listed as completed, including two Phase 3 studies in tardive dyskinesia and two Phase 2 studies in Tourette syndrome. No trials are currently listed as active.
Completed NBI-98854 trials include NCT02405091 and NCT02274558, both Phase 3 studies in adults with tardive dyskinesia, plus NCT02581865 in adults with Tourette syndrome and NCT02679079 in children and adolescents with Tourette syndrome. Across the listed trials, total enrollment was 659 participants.