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INGREZZA® (valbenazine) capsules provided reductions in tardive dyskinesia (TD) severity1-3
INGREZZA 80 mg provided rapid and significant reductions in TD severity by 6 weeks1-3
LS mean change from baseline in AIMS dyskinesia total score through 6 weeks (ITT population)1-3
- a P≤0.001 dose that was statistically significantly different from placebo to control for multiple comparisons.
- b P<0.01 nominal P value when controlled for multiple comparisons.
- * Exploratory analysis; P values provided for descriptive purposes: (cP≤0.001, dP<0.05).
AT 6 WEEKS: ~30% reduction in TD severity with INGREZZA 80 mg1-3,e
- e In a post hoc analysis of the primary efficacy endpoint of patients randomized to INGREZZA 80 mg at baseline through Week 6.
- AIMS, Abnormal Involuntary Movement Scale; BL, baseline; ITT, intent-to-treat; LS mean, least squares mean; SEM, standard error of mean.
- 6 WEEKS
Learn more about actor simulations of TD
INGREZZA provided sustained reductions in TD severity through 48 weeks1,4
Extension study of INGREZZA 40 mg and INGREZZA 80 mg (ITT population)1,3,4
AT 48 WEEKS: -39% reduction in TD severity with INGREZZA 80 mg1,4,a
- a 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.
- AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind, placebo-controlled; DFWO, drug-free washout; ITT, intent-to-treat.
- 48 WEEKS
AIMS score reduction of ≥50% was generally consistent through Week 484
Percentage of extension study patients with AIMS score improvement ≥50% from baseline through Week 482-4,a
- AIMS, Abnormal Involuntary Movement Scale; DBPC, double-blind, placebo-controlled; DFWO, drug-free washout.
AT 6 WEEKS
≥50% reduction in TD severity in 40% of patients with INGREZZA 80 mg2,a
AT 48 WEEKS
≥50% reduction in TD severity in 52.4% of patients with INGREZZA 80 mg4,b
INGREZZA clinical study design
A pivotal study in TD1-4
KINECT 3 was a phase 3, multicenter, randomized, double-blind, placebo-controlled (DBPC), parallel, fixed-dose study evaluating the efficacy, safety, and tolerability of 2 doses of INGREZZA (40 mg and 80 mg) compared to placebo, administered once daily (qd).
The study design included1,2,4:
- 6-week DBPC treatment period: Patients randomized 1:1:1 to INGREZZA 40 mg, INGREZZA 80 mg, or placebo
- 42-week DB treatment extension period, for up to 48 weeks of treatment. Patients receiving placebo were re-randomized 1:1 to INGREZZA 40 mg or INGREZZA 80 mg
- Patients initially randomized or re-randomized to the 80 mg group received 40 mg for the first week. Investigators could decrease the 80 mg dose once at any time during the study due to tolerability. Patients were discontinued if the new dose was not tolerated
- 4-week washout, for a total study duration of up to 52 weeks
- 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 compared to placebo
- 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 process
Secondary efficacy endpoint2
The key secondary endpoint was the mean Clinical Global Impression of Change scale for Tardive Dyskinesia (CGI-TD) score compared to placebo
- CGI-TD is a clinician-rated scale used to assess the overall global improvement of TD on a 7-point scale (ranged 1 [“very much improved”] to 7 [“very much worse”])
- 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)
- 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 data
- 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 used
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 sequence:
- 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
- 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 collected
- 66% (150/227) of patients had a primary psychiatric diagnosis of schizophrenia or schizoaffective disorder
- 34% (77/227) of patients had mood disorder
- In the clinical studies, patients were allowed to remain on their stable psychiatric and/or medical condition treatment regimen (including no changes to the dose and frequency of ongoing medications and no discontinuation of medications)
- The most common types of concomitant medications were
ACE inhibitors (25.1%)
INDICATION & USAGE
INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.
IMPORTANT SAFETY INFORMATION
INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.
WARNINGS & PRECAUTIONS
INGREZZA can cause somnolence. 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.
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.
INGREZZA may cause parkinsonism in patients with tardive dyskinesia. 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.
The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >Placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia. 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
REFERENCES: 1. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc; 2019. 2. 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. 3. Data on file. Neurocrine Biosciences, Inc. 4. 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.
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