Efficacy

Not an actual patient
Reductions in TD severity

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

Reductions in tardive dyslkinesia AIMS severity by 6 weeks with INGREZZA valbenazine INGREZZA® (valbenazine) reductions in tardive dyskinesia chart
  • 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.
Portrayal of tardive dyskinesia movements at baseline
Total AIMS score portrayed in video = 10 Total AIMS score portrayed in video = 7
  • BASELINE
  • 6 WEEKS
Not an actual patient

Learn more about actor simulations of TD

Primary efficacy endpoint (mean change from baseline in AIMS dyskinesia total score at Week 6)1-3

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.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.b

  • a Patients randomized to 80 mg started on 40 mg for 1 week.
  • b Safety population.

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

Reductions in tardive dyslkinesia AIMS severity by 48 weeks with INGREZZA valbenazine INGREZZA TD reduction through 48 weeks chart

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.
Portrayal of tardive dyskinesia movements at baseline
Total AIMS score portrayed in video = 10 Total AIMS score portrayed in video = 6
  • BASELINE
  • 48 WEEKS
Not an actual patient Learn more about actor simulations of TD

Extension study (6 to 52 weeks)1,3,4

The INGREZZA extension study evaluated the safety and tolerability of INGREZZA 40 mg and 80 mg, administered once daily. 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 52.1,3,4

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

Extension study ≥50% improvement from baseline AIMS score at week 48 with INGREZZA valbenazine
  • 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

a Not adjusted for multiplicity. Data presented for ITT analysis set. Treatment group comparison based on Cochran-Mantel-Haenszel test. P value vs placebo. b Intent-to-treat population.
Clinical study design

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
KINECT 3 study design through 52 weeks INGREZZA valbenazine placebo baseline AIMS score INGREZZA KINECT 3 study design chart
AIMS, Abnormal Involuntary Movement Scale; BL baseline, DBPC, double-blind, placebo-controlled; DFWO, drug-free washout.

Primary endpoint1-3

  • 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])

Statistical analysis2,3

  • 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

Study population1,2

  • 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

Concomitant medications2,3

  • 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
    • Antipsychotics (85.5%)
    • Antidepressants (66.5%)
    • Anticholinergics (37.0%)
    • Antiepileptics (35.2%)
    • Anxiolytics (27.7%)
    • ACE inhibitors (25.1%)