Efficacy

INGREZZA provided reductions in tardive dyskinesia (TD) severity1

INGREZZA 80 mg provided rapid and significant improvements in tardive dyskinesia (TD) severity by 6 weeks1,2

LS mean change from baseline in AIMS dyskinesia total score through 6 weeks (ITT population)1,2

INGREZZA® (valbenazine) reductions in tardive dyskinesia chart INGREZZA® (valbenazine) reductions in tardive dyskinesia chart
a P<0.05; b P<0.01; c P≤0.001 for INGREZZA vs placebo.2 d In a post hoc analysis of the primary efficacy endpoint of patients randomized to INGREZZA 80 mg at baseline through Week 6.1,3 * Dose that was statistically significantly different from placebo after adjusting for multiplicity.1 BL, baseline; ITT, intent-to-treat; LS mean, least squares mean.
  • BASELINE
  • 6 WEEKS
Total AIMS score portrayed in video=10 Total AIMS score portrayed in video=7 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)1,2

KINECT 3 was a phase 3, multicenter, randomized, double-blind, placebo-controlled (DBPC), parallel, fixed-dose study that evaluated 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 subjects with clinical diagnoses of schizophrenia, schizoaffective disorder, or mood disorder with moderate to severe neuroleptic-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 Participants randomized to 80 mg started on 40 mg for 1 week. b Safety population.

INGREZZA TD reductions through 48 weeks1,2

Extension study of INGREZZA 40 mg and INGREZZA 80 mg (ITT population)1,2

INGREZZA TD reduction through 48 weeks chart INGREZZA TD reduction through 48 weeks chart
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 6.1,3 AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind, placebo-controlled; DFWO, drug-free washout; ITT, intent-to-treat.
  • BASELINE
  • 48 WEEKS
Total AIMS score portrayed in video=10 Total AIMS score portrayed in video=6 Not an actual patient Learn more about actor simulations of TD

Extension phase (6 to 52 weeks)1,2

The INGREZZA extension study evaluated the safety and tolerability of INGREZZA 40 mg and 80 mg, administered once daily. The 6-week DBPC 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), subjects were re-consented to confirm their willingness to continue in the study. Subjects initially randomized to placebo were re-randomized (1:1) to receive either 40 mg or 80 mg INGREZZA, and subjects initially randomized to INGREZZA continued their current dose. Subjects re-randomized to 80 mg started on 40 mg for 1 week. Subjects then entered a 4-week posttreatment period with a final study visit at the end of Week 52.

AIMS score reduction by ≥50% from baseline at 6 weeks2

a Not adjusted for multiplicity. Data presented for ITT analysis set. Treatment group comparison based on Cochran-Mantel-Haenszel test. P value vs placebo.2,3

INGREZZA clinical study design1,2

A pivotal study in TD1,2

KINECT 3 was a phase 3, 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 included:

  • 6-week DBPC treatment period: Subjects randomized 1:1:1 to INGREZZA 40 mg, INGREZZA 80 mg, or placebo; subjects randomized to 80 mg started on 40 mg for 1 week
  • 42-week DB treatment extension period, for up to 48 weeks of treatment. Placebo subjects were re-randomized 1:1 to INGREZZA 40 mg or INGREZZA 80 mg; subjects re-randomized to 80 mg started on 40 mg for 1 week
  • 4-week washout, for a total duration of up to 52 weeks
INGREZZA KINECT 3 study design chart INGREZZA KINECT 3 study design chart

Primary endpoint1,2

  • The primary efficacy endpoint was the mean change from baseline 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

  • The primary efficacy analysis set was the intent-to-treat (ITT) analysis set, which included all subjects 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)
  • Subjects who discontinued from the study prior to the scheduled Week 2 visit 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 subjects included:
    • 234 medically stable male and female subjects
    • 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–5])
  • During the 6-week study period, 2 subjects withdrew (1 subject in the placebo group and 1 subject in the INGREZZA 40 mg group), and 5 subjects 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, subjects 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 (25.6%)
  • Reductions in TD severity

    INGREZZA provided reductions in tardive dyskinesia (TD) severity1

    INGREZZA 80 mg provided rapid and significant improvements in tardive dyskinesia (TD) severity by 6 weeks1,2

    LS mean change from baseline in AIMS dyskinesia total score through 6 weeks (ITT population)1,2

    INGREZZA® (valbenazine) reductions in tardive dyskinesia chart INGREZZA® (valbenazine) reductions in tardive dyskinesia chart
    a P<0.05; b P<0.01; c P≤0.001 for INGREZZA vs placebo.2 d In a post hoc analysis of the primary efficacy endpoint of patients randomized to INGREZZA 80 mg at baseline through Week 6.1,3 * Dose that was statistically significantly different from placebo after adjusting for multiplicity.1 BL, baseline; ITT, intent-to-treat; LS mean, least squares mean.
    • BASELINE
    • 6 WEEKS
    Total AIMS score portrayed in video=10 Total AIMS score portrayed in video=7 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)1,2

    KINECT 3 was a phase 3, multicenter, randomized, double-blind, placebo-controlled (DBPC), parallel, fixed-dose study that evaluated 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 subjects with clinical diagnoses of schizophrenia, schizoaffective disorder, or mood disorder with moderate to severe neuroleptic-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 Participants randomized to 80 mg started on 40 mg for 1 week. b Safety population.

    INGREZZA TD reductions through 48 weeks1,2

    Extension study of INGREZZA 40 mg and INGREZZA 80 mg (ITT population)1,2

    INGREZZA TD reduction through 48 weeks chart INGREZZA TD reduction through 48 weeks chart
    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 6.1,3 AIMS, Abnormal Involuntary Movement Scale; BL, baseline; DBPC, double-blind, placebo-controlled; DFWO, drug-free washout; ITT, intent-to-treat.
    • BASELINE
    • 48 WEEKS
    Total AIMS score portrayed in video=10 Total AIMS score portrayed in video=6 Not an actual patient Learn more about actor simulations of TD

    Extension phase (6 to 52 weeks)1,2

    The INGREZZA extension study evaluated the safety and tolerability of INGREZZA 40 mg and 80 mg, administered once daily. The 6-week DBPC 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), subjects were re-consented to confirm their willingness to continue in the study. Subjects initially randomized to placebo were re-randomized (1:1) to receive either 40 mg or 80 mg INGREZZA, and subjects initially randomized to INGREZZA continued their current dose. Subjects re-randomized to 80 mg started on 40 mg for 1 week. Subjects then entered a 4-week posttreatment period with a final study visit at the end of Week 52.

    AIMS score reduction by ≥50% from baseline at 6 weeks2

    a Not adjusted for multiplicity. Data presented for ITT analysis set. Treatment group comparison based on Cochran-Mantel-Haenszel test. P value vs placebo.2,3
  • Clinical study design

    INGREZZA clinical study design1,2

    A pivotal study in TD1,2

    KINECT 3 was a phase 3, 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 included:

    • 6-week DBPC treatment period: Subjects randomized 1:1:1 to INGREZZA 40 mg, INGREZZA 80 mg, or placebo; subjects randomized to 80 mg started on 40 mg for 1 week
    • 42-week DB treatment extension period, for up to 48 weeks of treatment. Placebo subjects were re-randomized 1:1 to INGREZZA 40 mg or INGREZZA 80 mg; subjects re-randomized to 80 mg started on 40 mg for 1 week
    • 4-week washout, for a total duration of up to 52 weeks
    INGREZZA KINECT 3 study design chart INGREZZA KINECT 3 study design chart

    Primary endpoint1,2

    • The primary efficacy endpoint was the mean change from baseline 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

    • The primary efficacy analysis set was the intent-to-treat (ITT) analysis set, which included all subjects 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)
    • Subjects who discontinued from the study prior to the scheduled Week 2 visit 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 subjects included:
      • 234 medically stable male and female subjects
      • 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–5])
    • During the 6-week study period, 2 subjects withdrew (1 subject in the placebo group and 1 subject in the INGREZZA 40 mg group), and 5 subjects 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, subjects 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 (25.6%)