Consistent efficacy in schizophrenia across 3 pivotal trials1-4

VRAYLAR demonstrated symptom improvement across 3 pivotal trials based on mean reduction in Positive and Negative Syndrome Scale (PANSS) total score at Week 6

Study 1
(Durgam 2014)1,2
Least squares (LS) mean change from baseline in PANSS total score -19.4 (1.5 mg/day)
-20.7 (3 mg/day)
-22.3 (4.5 mg/day)
-11.8 (placebo)
P<0.001 vs placebo for each
Study 2
(Durgam 2015)1,3
Least squares (LS) mean change from baseline in PANSS total score -20.2 (3 mg/day)
-23.0 (6 mg/day)
-14.3 (placebo)
P<0.01 vs placebo for each
Study 3
(Kane 2015)1,4
Least squares (LS) mean change from baseline in PANSS total score -22.8 (3-6 mg/day)
-25.9 (6-9 mg/day)
-16.0 (placebo)
P<0.01 vs placebo for each

Mean baseline values were 97.1 (1.5 mg/day), 97.2 (3 mg/day), 96.7 (4.5mg/day), and 97.3 (placebo) in Study 1; 96.1 (3 mg/day), 95.7 (6 mg/day), and 96.5 (placebo) in Study 2; and 96.3 (3-6 mg/day), 96.3 (6-9 mg/day), and 96.6 (placebo) in Study 3.1-4

STUDY DESIGNS: Three 6-week, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of VRAYLAR in adult patients (18-60 years old) with acute exacerbation of schizophrenia, based on Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, Text Revision (DSM-IV-TR) criteria. The primary statistical analyses were conducted using the last-observation-carried-forward (LOCF) approach for Study 1 and a mixed-effects model for repeated measures (MMRM) approach for Studies 2 and 3.1-4

  • Maximum recommended dose of VRAYLAR is 6 mg/day. A dose-related increase in certain adverse reactions, particularly above 6 mg, was observed1

VRAYLAR demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total score

Study 1 (Durgam 2014): Change from baseline in PANSS total score at Week 61,2

Baseline mean: Placebo: 97.3; VRAYLAR 1.5 mg/day: 97.1; VRAYLAR 3 mg/day: 97.2; VRAYLAR 4.5 mg/day: 96.7.

It is unknown if the statistically significant differences observed at time points earlier than 6 weeks represent clinically relevant treatment effects.

  • VRAYLAR 1.5 mg/day: 64% improvement vs placebo
  • VRAYLAR 3 mg/day:
    75%
    improvement vs placebo
  • VRAYLAR 4.5 mg/day: 89% improvement vs placebo

STUDY 1: A 6-week, randomized, double-blind, placebo-controlled trial (N = 711) to determine the efficacy and safety of VRAYLAR in adult patients (18-60 years old) with acute exacerbation of schizophrenia, based on Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, Text Revision (DSM-IV-TR) criteria. Patients were randomized to 3 fixed doses of VRAYLAR (1.5, 3, or 4.5 mg/day; n = 140, n = 140, and n = 145, respectively), active control risperidone for assay sensitivity (n = 138), or placebo (n = 148). The primary endpoint was change from baseline to Week 6 in PANSS total score, using the last-observation-carried-forward (LOCF) approach.1,2


Study 2 (Durgam 2015): Change from baseline in PANSS total score at Week 61,3

Baseline mean: Placebo: 96.5; VRAYLAR 3 mg/day: 96.1; VRAYLAR 6 mg/day: 95.7.

It is unknown if the statistically significant differences observed at time points earlier than 6 weeks represent clinically relevant treatment effects.

  • VRAYLAR 3 mg/day: 41% improvement vs placebo
  • VRAYLAR 6 mg/day: 61% improvement vs placebo

STUDY 2: A 6-week, randomized, double-blind, placebo-controlled trial (N =  604) to determine the efficacy and safety of VRAYLAR in adult patients (18-60 years old) with acute exacerbation of schizophrenia, based on DSM-IV-TR criteria. Patients were randomized to 2 fixed doses of VRAYLAR (3 or 6 mg/day; n = 151 and n = 154, respectively), active control aripiprazole for assay sensitivity (n = 150), or placebo (n = 149). The primary endpoint was change from baseline to Week 6 in PANSS total score using a mixed-effects model for repeated measures (MMRM) approach.1,3


Study 3 (Kane 2015): Change from baseline in PANSS total score at Week 61,4

There was a significant reduction in mean PANSS total score from baseline with VRAYLAR 3-6 mg/day and VRAYLAR 6-9 mg/day vs placebo (-22.8 [P = 0.003] and -25.9 [P < 0.001] vs -16.0, respectively).

Improvement vs placebo: VRAYLAR 3-6 mg/day = 43%; VRAYLAR 6-9 mg/day = 62%.

Baseline mean: Placebo: 96.6; VRAYLAR 3-6 mg/day: 96.3; VRAYLAR 6-9 mg/day: 96.3.

STUDY 3: A 6-week, randomized, double-blind, placebo-controlled trial (N = 439) to determine the efficacy and safety of VRAYLAR in adult patients (18-60 years old) with acute exacerbation of schizophrenia, based on DSM-IV-TR criteria. Patients were randomized to 2 fixed-flexible doses of VRAYLAR (3-6 or 6-9 mg/day; n = 147 and n = 147, respectively), or placebo (n = 145). The primary endpoint was change from baseline to Week 6 in PANSS total score using the MMRM approach.1,4


PANSS is a 30-item, clinician-rated scale that measures the following symptoms1,6:

Each item is rated on a scale of 1 (absent) to 7 (extreme). The PANSS total score ranges from 30 to 210, with higher scores reflecting greater severity.

Positive symptoms
  • Delusions
  • Conceptual disorganization
  • Hallucinatory behavior
  • Excitement
  • Grandiosity
  • Suspiciousness
  • Hostility
Negative symptoms
  • Blunted affect
  • Emotional withdrawal
  • Poor rapport
  • Passive-apathetic social withdrawal
  • Difficulty in abstract thinking
  • Lack of spontaneity and flow of conversation
  • Stereotyped thinking
General psychopathology symptoms
  • Somatic concern
  • Anxiety
  • Guilt feelings
  • Tension
  • Mannerisms and posturing
  • Depression
  • Motor retardation
  • Uncooperativeness
  • Unusual thought content
  • Disorientation
  • Poor attention
  • Lack of judgment and insight
  • Disturbance of volition
  • Poor impulse control
  • Preoccupation
  • Active social avoidance

The efficacy of VRAYLAR was based on the PANSS total score, not on any individual component of the scale.1