Efficacy in adults with tardive dyskinesia
SELECT EFFICACY ENDPOINT:
6-week reduction
6-week response
48-week reduction
6-week reduction
6-week response
48-week reduction
Only INGREZZA offers tardive dyskinesia (TD) control made simple in just 6 weeks,
with results as early as 2 weeks1,2
LS mean change from baseline in AIMS dyskinesia total score through 6 weeks (ITT population)1-3
STUDY DESIGN
| * | Based on modeling and simulation. The LS mean is adjusted for baseline AIMS score and disease category and is shown for consistency with 40 mg and 80 mg observed values from the KINECT 3 study. |
| a | P≤0.001 dose that was statistically significantly different from placebo to control for multiple comparisons. |
Mean baseline AIMS score (SD): placebo 9.9 (4.3), 40 mg 9.8 (4.1), 80 mg 10.4 (3.6). |
|
AIMS, Abnormal Involuntary Movement Scale; BL, baseline; ITT, intent-to-treat; LS mean, least squares mean; SD, standard deviation; SEM, standard error of mean. |
|
See more results for INGREZZA
See why long-term treatment with INGREZZA 40 mg may be appropriate for some patients.a Review results of the KINECT 4 study—a phase 3, long-term, open-label study designed to be reflective of TD treatment in clinical practice.6
aRecommended dosage is 80 mg once daily, but patients may be maintained or adjusted back to 40 mg based on individual treatment needs. |
INGREZZA 80 mg reduced uncontrolled movements in 7 of 10 patients at 6 weeks1,3,†
Percent of patients with specified magnitude of AIMS total score improvement at the end of Week 61,3,†
STUDY DESIGN
| † | Post hoc analysis included patients who had a baseline and a Week 6 AIMS total score. Reduction in uncontrolled movements as assessed by ≥1-point decrease in AIMS total score (n=70). |
Mean baseline AIMS score (SD): placebo 9.9 (4.3), 40 mg 9.8 (4.1), 80 mg 10.4 (3.6). |
AIMS, Abnormal Involuntary Movement Scale; SD, standard deviation. |
STUDY DESIGN
See more results for INGREZZA
See why long-term treatment with INGREZZA 40 mg may be appropriate for some patients.a Review results of the KINECT 4 study—a phase 3, long-term, open-label study designed to be reflective of TD treatment in clinical practice.6
aRecommended dosage is 80 mg once daily, but patients may be maintained or adjusted back to 40 mg based on individual treatment needs. |
Patients remaining on INGREZZA saw substantial reductions in TD severity1,4
Extension study of INGREZZA 40 mg and INGREZZA 80 mg (ITT population)1,3,4
AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind placebo-controlled; DFWO, drug-free washout; ITT, intent-to-treat. |
| ‡ | In a post hoc analysis that included patients randomized to INGREZZA 80 mg at baseline and those who were re-randomized to INGREZZA 80 mg at Week 6 (n=65). |
STUDY DESIGN
AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind placebo-controlled; DFWO, drug-free washout; ITT, intent-to-treat. |
See more results for INGREZZA
See why long-term treatment with INGREZZA 40 mg may be appropriate for some patients.a Review results of the KINECT 4 study—a phase 3, long-term, open-label study designed to be reflective of TD treatment in clinical practice.6
aRecommended dosage is 80 mg once daily, but patients may be maintained or adjusted back to 40 mg based on individual treatment needs. |
Watch expert perspective videos on INGREZZA
Featuring Amy LaCouture, RN, BSN, PMHNP-BC
These videos were sponsored and developed by Neurocrine Biosciences.
The speaker is a paid consultant of Neurocrine Biosciences.
Why I choose INGREZZA for my adult patients with tardive dyskinesia (TD)
Case study: John, a patient with schizophrenia and tardive dyskinesia (TD)
SIMPLE FROM
THE START
The only VMAT2 inhibitor that offers an effective starting dosage you can adjust based on response and tolerability1
EXPLORE DOSINGSEE REAL-WORLD RESULTS
WITH INGREZZA
View videos of real-world patients with TD treated with INGREZZA
VIEW CASES
INGREZZA CLINICAL
SAFETY DATA
INGREZZA was studied across a broad range of TD patients
REVIEW SAFETYREFERENCES:
- INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc.
- Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484.
- Data on file. Neurocrine Biosciences, Inc.
- Factor SA, Remington G, Comella CL, et al. The effects of valbenazine in participants with tardive dyskinesia: results of the 1-year KINECT 3 extension study. J Clin Psychiatry. 2017;78(9):1344-1350.
- Correll CU, Cutler AJ, Kane JM, McEvoy JP, Liang GS, O’Brien CF. Characterizing treatment effects of valbenazine for tardive dyskinesia: additional results from the KINECT 3 study. J Clin Psychiatry. 2018;80(1):18m12278.
- Marder SR, Singer C, Lindenmayer JP, et al. A phase 3, 1-year, open-label trial of valbenazine in adults with tardive dyskinesia. J Clin Psychopharmacol. 2019;39(6):620-627.
Important Information
INDICATION & USAGE
INGREZZA® (valbenazine) capsules is indicated in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease.
IMPORTANT SAFETY INFORMATION
Depression and Suicidality in Patients with Huntington’s Disease: VMAT2 inhibitors, including INGREZZA, can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidal ideation and behavior and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in patients with Huntington’s disease.
CONTRAINDICATIONS
INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA.
WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions, including cases of angioedema involving the larynx, glottis, lips, and eyelids, have been reported in patients after taking the first or subsequent doses of INGREZZA. Angioedema associated with laryngeal edema can be fatal. If any of these reactions occur, discontinue INGREZZA.
Somnolence and Sedation
INGREZZA can cause somnolence and sedation. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.
QT Prolongation
INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.
Neuroleptic Malignant Syndrome
A potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with drugs that reduce dopaminergic transmission, including INGREZZA. The management of NMS should include immediate discontinuation of INGREZZA, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems. If treatment with INGREZZA is needed after recovery from NMS, patients should be monitored for signs of recurrence.
Parkinsonism
INGREZZA may cause parkinsonism. Parkinsonism has also been observed with other VMAT2 inhibitors. Reduce the dose or discontinue INGREZZA treatment in patients who develop clinically significant parkinson-like signs or symptoms.
ADVERSE REACTIONS
The most common adverse reaction in patients with tardive dyskinesia (≥5% and twice the rate of placebo) is somnolence.
The most common adverse reactions in patients with Huntington’s disease (>5% and twice the rate of placebo) are somnolence/lethargy/sedation, urticaria, rash, and insomnia.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see INGREZZA full Prescribing Information, including Boxed Warning.
Important Safety Information
Depression and Suicidality in Patients with Huntington’s Disease: VMAT2 inhibitors, including INGREZZA, can increase the risk of depression and suicidal thoughts and
Important Information
INDICATION & USAGE
INGREZZA® (valbenazine) capsules is indicated in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease.
IMPORTANT SAFETY INFORMATION
Depression and Suicidality in Patients with Huntington’s Disease: VMAT2 inhibitors, including INGREZZA, can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidal ideation and behavior and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in patients with Huntington’s disease.
Important Information
INDICATION & USAGE
INGREZZA® (valbenazine) capsules is indicated in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington’s disease.
IMPORTANT SAFETY INFORMATION
Depression and Suicidality in Patients with Huntington’s Disease: VMAT2 inhibitors, including INGREZZA, can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidal ideation and behavior and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in patients with Huntington’s disease.
CONTRAINDICATIONS
INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA.
WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions, including cases of angioedema involving the larynx, glottis, lips, and eyelids, have been reported in patients after taking the first or subsequent doses of INGREZZA. Angioedema associated with laryngeal edema can be fatal. If any of these reactions occur, discontinue INGREZZA.
Somnolence and Sedation
INGREZZA can cause somnolence and sedation. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.
QT Prolongation
INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.
Neuroleptic Malignant Syndrome
A potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with drugs that reduce dopaminergic transmission, including INGREZZA. The management of NMS should include immediate discontinuation of INGREZZA, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems. If treatment with INGREZZA is needed after recovery from NMS, patients should be monitored for signs of recurrence.
Parkinsonism
INGREZZA may cause parkinsonism. Parkinsonism has also been observed with other VMAT2 inhibitors. Reduce the dose or discontinue INGREZZA treatment in patients who develop clinically significant parkinson-like signs or symptoms.
ADVERSE REACTIONS
The most common adverse reaction in patients with tardive dyskinesia (≥5% and twice the rate of placebo) is somnolence.
The most common adverse reactions in patients with Huntington’s disease (>5% and twice the rate of placebo) are somnolence/lethargy/sedation, urticaria, rash, and insomnia.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see INGREZZA full Prescribing Information, including Boxed Warning.
KINECT® 3: INGREZZA pivotal study design1-4
Study overview
Primary efficacy endpoint was mean change from baseline in AIMS dyskinesia total score at Week 6 for 80 mg compared to placebo1
KINECT 3 was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel, fixed-dose study to evaluate the efficacy, safety, and tolerability of INGREZZA 40 mg and 80 mg, administered once daily, compared to placebo.2,a
The study included 234 medically stable patients with a clinical diagnosis of schizophrenia, schizoaffective disorder, or mood disorder with moderate to severe DRBA-induced TD: 66% (150/227) of patients had a primary psychiatric diagnosis of schizophrenia or schizoaffective disorder; 34% (77/227) of patients had mood disorder.2,4,b
Extension study (6 to 52 weeks)
The INGREZZA extension study evaluated the safety and tolerability of INGREZZA 40 mg and 80 mg, administered once daily.4
The 6-week DBPC study period was followed by a double-blind INGREZZA extension period for 42 weeks (total treatment period 48 weeks). At the end of Week 6 (end of the DBPC treatment period), patients were re-consented to confirm their willingness to continue in the study. Patients initially randomized to placebo were re-randomized (1:1) to receive either 40 mg or 80 mg INGREZZA, and patients initially randomized to INGREZZA continued their current dose. Patients re-randomized to 80 mg started on 40 mg for 1 week. Patients then entered a 4-week posttreatment period with a final study visit at the end of Week 52.2-4
| a | Patients randomized to 80 mg started on 40 mg for 1 week. |
| b | Safety population. |
AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind placebo-controlled; DFWO, drug-free washout. |
Study endpoints
Primary endpoint
- The primary efficacy endpoint was the mean change from baseline (CFB) at the end of Week 6 in the Abnormal Involuntary Movement Scale (AIMS) dyskinesia total score for INGREZZA 80 mg compared to placebo1
- The AIMS video recordings at baseline and throughout the study were reviewed at each study visit and scored by blinded, central AIMS video raters who scored the AIMS dyskinesia total score (sum of items 1–7 on AIMS) using a triple-blind consensus scoring process2
Secondary efficacy endpoint
- The key secondary endpoint was the mean Clinical Global Impression of Change scale for Tardive Dyskinesia (CGI-TD) score compared to placebo2
- CGI-TD is a clinician-rated scale used to assess the overall global improvement of TD on a 7-point Likert scale (ranged 1 [very much improved] to 7 [very much worse])2
Statistical analysis
- The primary efficacy analysis set was the intent-to-treat (ITT) analysis set, which included all patients in the safety analysis set who had a baseline (Day –1) AIMS dyskinesia total score value and at least one postbaseline AIMS dyskinesia total score value reported during the double-blind, placebo-controlled treatment period (ie, after randomization through Week 6 of the study)3
- Patients who discontinued from the study prior to the scheduled Week 2 visit should have had AIMS data for the early termination (ET) visit, and were therefore expected to be included in this analysis set (the ET visit data in this case was treated as Week 2 data). The ITT analysis set was used for summaries and analyses of efficacy data3
- In order to control the family-wise error rate for the AIMS and CGI-TD endpoints, as well as for the 2 INGREZZA treatment group comparisons to placebo, a fixed-sequence testing procedure was used2
- The sequence of tests that were performed at Week 6 is summarized, in order, below. For each endpoint, a P value of ≤0.05 was required to continue the test sequence2,3:
- AIMS dyskinesia total score mean CFB: INGREZZA 80 mg treatment group vs placebo treatment group
- CGI-TD mean score: INGREZZA 80 mg treatment group vs placebo treatment group
- AIMS dyskinesia total score mean CFB: INGREZZA 40 mg treatment group vs placebo treatment group
- CGI-TD mean score: INGREZZA 40 mg treatment group vs placebo treatment group
Study population
-
Enrolled patients:
- 234 medically stable males and females
- Aged 18 to 85
- Clinical diagnoses of schizophrenia or schizoaffective disorder with neuroleptic-induced TD or mood disorder with neuroleptic-induced TD (based on the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders [DSM–IV])
- During the 6-week study period, 2 patients withdrew (1 patient in the placebo group and 1 patient in the INGREZZA 40 mg group), and 5 patients had no postbaseline safety data collected1,2
- 66% (150/227) of patients had a primary psychiatric diagnosis of schizophrenia or schizoaffective disorder
- 34% (77/227) of patients had mood disorder