Consistent efficacy in bipolar mania across 3 pivotal trials1-4

VRAYLAR demonstrated symptom improvement across 3 pivotal trials based on mean reduction in Young Mania Rating Scale (YMRS) total score at Week 3

Study 1
(Calabrese 2015)1,2
Least squares (LS) mean change from baseline in YMRS total score -18.6 (3-6 mg/day)
-18.5 (6-12 mg/day)
-12.5 (placebo)
P<0.001 vs placebo for each
Study 2
(Durgam 2015)1,3
Least squares (LS) mean change from baseline in YMRS total score -15.0 (3-12 mg/day)
-8.9 (placebo)
P<0.001 vs placebo
Study 3
(Sachs 2015)1,4
Least squares (LS) mean change from baseline in YMRS total score -19.6 (3-12 mg/day)
-15.3 (placebo)
P<0.001 vs placebo

Mean baseline values were 33.2 (3-6 mg/day), 32.9 (6-12 mg/day), and 32.6 (placebo) in Study 1; 30.6 (3-12 mg/day) and 30.2 (placebo) in Study 2; and 32.3 (3-12 mg/day) and 32.1 (placebo) in Study 3.1-4

STUDY DESIGNS: Three 3-week, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of VRAYLAR in adult patients (18-65 years old) with manic or mixed episodes of bipolar I disorder, with or without psychotic features, based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. The primary statistical analyses were conducted using a mixed-effects model for repeated measures (MMRM) approach for Studies 1 and 3 and the last-observation-carried-forward (LOCF) approach for Study 2.1-4

  • Maximum recommended dose of VRAYLAR is 6 mg/day. Doses above 6 mg did not appear to have additional benefit over lower doses and a dose-related increase in certain adverse reactions was observed1

Study 1 (Calabrese 2015): Change from baseline in YMRS total score at 3 weeks1,2

Baseline mean: Placebo: 32.6; VRAYLAR 3-6 mg/day: 33.2; VRAYLAR 6-12 mg/day: 32.9.

It is unknown if the statistically significant differences observed at time points earlier than Day 21 represent clinically relevant treatment effects.

  • VRAYLAR 6-12 mg/day: 48% improvement vs placebo
  • VRAYLAR 3-6 mg/day: 49% improvement vs placebo

STUDY 1: A 3-week, randomized, double-blind, placebo-controlled trial (N = 492) to determine the efficacy and safety of VRAYLAR in adult patients (18-65 years old) with manic or mixed episodes of bipolar I disorder, with or without psychotic symptoms, based on DSM-IV-TR criteria. Patients were randomized to 2 fixed-flexible doses of VRAYLAR (3-6 or 6-12 mg/day; n = 165 and n = 167, respectively) or placebo (n = 160). The primary endpoint was change from baseline to Week 3 in YMRS total score using an MMRM approach.1,2


Study 2 (Durgam 2015): Change from baseline in YMRS total score at 3 weeks1,3

Baseline mean: Placebo: 30.2; VRAYLAR 3-12 mg/day: 30.6.

It is unknown if the statistically significant differences observed at time points earlier than Day 21 represent clinically relevant treatment effects.

  • VRAYLAR 3-12 mg/day: 69% improvement vs placebo

STUDY 2: A 3-week, randomized, double-blind, placebo-controlled trial (N = 235) to determine the efficacy and safety of VRAYLAR in adult patients (18-65 years old) with manic or mixed episodes of bipolar I disorder, with or without psychotic symptoms, based on DSM-IV-TR criteria. Patients were randomized to VRAYLAR (3-12 mg/day; n = 118) or placebo (n = 117). The primary endpoint was change from baseline to Week 3 in YMRS total score using an LOCF approach.1,3


Study 3 (Sachs 2015): Change from baseline in YMRS total score at 3 weeks1,3

VRAYLAR 3-12 mg/day significantly reduced mean YMRS total score from baseline vs placebo (-19.6 vs -15.3, respectively; P < 0.001), which represented a 28% improvement vs placebo.

Baseline mean: Placebo: 32.1; VRAYLAR 3-12 mg/day: 32.3.

STUDY 3: A 3-week, randomized, double-blind, placebo-controlled trial (N = 310) to determine the efficacy and safety of VRAYLAR in adult patients (18-65 years old) with manic or mixed episodes of bipolar I disorder, with or without psychotic symptoms, based on DSM-IV-TR criteria. Patients were randomized to VRAYLAR (3-12 mg/day; n = 158) or placebo (n = 152). The primary endpoint was change from baseline to Week 3 in YMRS total score using an MMRM approach.1,4


YMRS is a clinician-rated scale that measures 11 manic symptoms of bipolar disorder1,6

Scale ranges from 0 (no manic features) to 60 (maximum score) and includes the symptoms below (higher score reflects greater severity).6

  • Elevated mood
  • Increased motor activity-energy
  • Sexual interest
  • Sleep
  • Irritability
  • Speech (rate and amount)
  • Language-thought disorder
  • Content
  • Disruptive-aggressive behavior
  • Appearance
  • Insight

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