Drugs

Drug Trials Snapshots: VRAYLAR for the treatment of schizophrenia

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the VRAYLAR Prescribing Information for complete information.

VRAYLAR(cariprazine)
(vrāy-lar)
Forest Laboratories, LLC
Approval date: September 17, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

VRAYLAR is used for the treatment of schizophrenia.

Schizophrenia is a brain disorder characterized by hearing voices, believing other people are reading one’s mind or controlling one’s thoughts, and being suspicious or withdrawn.

How is this drug used?

VRAYLAR is a capsule that is taken once a day.

What are the benefits of this drug?

VRAYLAR reduced symptoms of schizophrenia.

What are the benefits of this drug?

The table below summarizes the primary efficacy endpoints. This was based on the mean change in the Positive and Negative Syndrome Scale (PANSS) total score after 6 weeks. The population represents the Full Analysis Set (FAS) and consists of all randomized patients who received at least one dose of study drug and had at least one post-randomization efficacy evaluation for PANSS total score.

Table 2. Summary of Efficacy Results (FAS population)

Trial
Number
Treatment GroupPrimary Efficacy Endpoint: PANSS Total
Mean Baseline Score (SD)LS Mean Change from Baseline (SE)Placebo-subtracted Differencea (95% CI)
Trial 1VRAYLAR (1.5 mg/day)*97.1 (9.1)-19.4 (1.6)-7.6 (-11.8, -3.3)
VRAYLAR (3 mg/day)*97.2 (8.7)-20.7 (1.6)-8.8 (-13.1, -4.6)
VRAYLAR (4.5 mg/day)*96.7 (9.0)-22.3 (1.6)-10.4 (-14.6, -6.2)
Placebo97.3 (9.2)-11.8 (1.5)--
Trial 2VRAYLAR (3 mg/day)*96.1 (8.7)-20.2 (1.5)-6.0 (-10.1, -1.9)
VRAYLAR (6 mg/day)*95.7 (9.4)-23.0 (1.5)-8.8 (-12.9, -4.7)
Placebo96.5 (9.1)-14.3 (1.5)--
Trial 3VRAYLAR (3-6 mg/day)*96.3 (9.3)-22.8 (1.6)-6.8 (-11.3, -2.4)
VRAYLAR (6-9 mg/day)*†96.3 (9.0)-25.9 (1.7)-9.9 (-14.5, -5.3)
Placebo96.6 (9.3)-16.0 (1.6)--

FAS=Full Analysis Set
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval, not adjusted for multiple comparisons.
aDifference (drug minus placebo) in least-squares mean change from baseline.
*Doses that are statistically significantly superior to placebo
The maximum approved dose is 6 mg/day
Source: Prescribing Information, Section 14, Table 13

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

Subgroup analyses were conducted for sex and race. Analysis for different age groups was not done because all patients were between 18 and 65 years of age.

  • Sex: VRAYLAR worked similarly in men and women.
  • Race: VRAYLAR worked similarly in all races studied.
  • Age: All patients were between 18 and 65 years of age. Differences in how well VRAYLAR worked in patients below and above 65 years of age could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The tables below summarize the responses to VRAYLAR by sex and race subgroups for the FAS population which includes all randomized patients who received at least one dose of study drug and had at least one post-randomization efficacy evaluation for PANSS total score.

Table 3. Subgroup Analysis of Primary Endpoint-PANNS (by sex)

Sex          Trial 1          Trial 2          Trial 3
VRAYLAR
1.5 mg
VRAYLAR  3 mgVRAYLAR 4.5 mgVRAYLAR 3 mgVRAYLAR 6 mgVRAYLAR 3-6 mgVRAYLAR
6-9 mg†
Male
Placebo-subtracted difference,  Mean (SE)
-7.6 (3.0)-9.1 (2.9)-6.5 (2.5)-8.6 (2.6)-9.4 (2.8)-6.9 (2.5)-8.1 (2.5)
Female
Placebo-subtracted difference,  Mean (SE)
-8.2 (4.0)-9.2 (4.1)-3.5 (3.7)-6.3 (3.5)-13.8 (3.9)-6.1 (4.6)-7.1 (4.7)

The maximum approved dose is 6 mg/day
Source: Company Trial Data

Table 4. Subgroup Analysis of Primary Endpoint –PANSS (by race)

Race          Trial 1          Trial 2          Trial 3
VRAYLAR
1.5 mg
VRAYLAR  3 mgVRAYLAR 4.5 mgVRAYLAR 3 mgVRAYLAR 6  mgVRAYLAR 3-6 mgVRAYLAR
6-9 mg†
White
Placebo-subtracted difference,  Mean (SE)
-4.5 (3.2)-6.9 (3.3)-8.2 (3.0)-9.1 (2.5)-9.3 (2.5)-11.9 (4.6)-13.4 (4.9)
All other races
Placebo-subtracted difference,  Mean (SE)
-11.5 (3.6)-11.5 (3.5)-13.4 (3.4)2.2
(4.0)
-3.7 (4.0)-5.4 (2.5)-6.6 (2.5)

The maximum approved dose is 6 mg/day
Source: Company Trial Data

What are the possible side effects?

The most common side effects of VRAYLAR are unintentional trembling or shaking movements in one or more parts of your body (called a tremor), slurred speech, and involuntary muscle movements.

What are the possible side effects?

The table below summarizes adverse reactions in the Safety population defined as all patients who receive at least at least one injection dose of study drug.

Table 3. Adverse Reactions that Occurred in 2% or more of VRAYLAR-Treated Patients and at Greater Incidence than in the Placebo-Treated Patients

System Organ Class /
Preferred Term
Placebo
(N= 584)
(%)
VRAYLAR*
1.5-3 mg/day
(N=539)
(%)
4.5-6 mg/day
(N=575)
(%)
9-12 mg/day
(N=203)
(%)
Cardiac Disorders
Tachycardiaa1223
Gastrointestinal Disorders
Constipation56710
Nausea5578
Vomiting3455
General Disorders/Administration Site Conditions
Fatigueb1232
Investigations
Weight increased1323
Musculoskeletal and Connective Tissue Disorders
Back pain2332
Nervous System Disorders
Akathisia491314
Extrapyramidal Symptomsc8151920
Somnolenced65810
Dizziness2355
Psychiatric Disorders
Insomniae11121311
Restlessness3465
Anxiety4653
Vascular Disorders
Hypertensionf1236

Note: Figures rounded to the nearest integer
* Data shown by modal daily dose, defined as most frequently administered dose per patient
a Tachycardia terms: heart rate increased, sinus tachycardia, tachycardia
b Fatigue terms: asthenia, fatigue
c Extrapyramidal Symptoms terms: bradykinesia, cogwheel rigidity, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, masked facies, muscle rigidity, muscle tightness, musculoskeletal stiffness, oculogyric crisis, oromandibular dystonia, parkinsonism, salivary hypersecretion, tardive dyskinesia, tremor, trismus
d Somnolence terms: hypersomnia, sedation, somnolence
e Insomnia terms: initial insomnia, insomnia, middle insomnia, terminal insomnia
The maximum approved dose is 6 mg/day
Source: Prescribing Information, Section 6 Table 7

Were there any differences in side effects among sex, race and age?

Subgroup analyses were conducted for sex and race.

  • Sex: The risk of side effects appeared to be similar in men and women.
  • Race: The risk of side effects appeared to be similar among different races.
  • Age: All patients were between 18 and 65 years of age. Differences in side effects in patients below and above 65 years of age could not be determined.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes extrapyramidal adverse events in the Safety population defined as all patients who received at least at least one dose of study drug.

Table 4. Subgroup Analysis of Extrapyramidal Symptoms

Demographic ParametersPlacebo


n/N
(%)
VRAYLAR
1.5-3 mg

n/N
(%)
VRAYLAR
4.5-6 mg

n/N
(%)
VRAYLAR†
9-12 mg

n/N
 (%)
Any EPS TAES*79/584
(14)
128/539 (24)182/575
(32)
66/203 (33)
Sex
 Male56/415
(14)
84/372
(23)
135/422
(32)
49/151 (33)
 Female23/169
(14)
44/167
(26)
47/153
(31)
17/52 (33)
Race
 White28/237
(12)
48/278
(17)
68/247
(28)
16/49 (33)
 All other races48/335
(14)
74/244
(30)
110/311
(35)
50/154 (33)

*Extrapyramidal symptoms treatment emergent adverse events
The maximum approved dose is 6 mg/day
Source: Company Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved VRAYLAR based on evidence from three clinical trials that enrolled a total of 1754 patients with schizophrenia. The trials were conducted in the United States, Europe, Asia, South America, and Africa.

The figure below summarizes how many men and women participated in the clinical trials. The population represents any patient who received study treatment (also known as the safety population).

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were enrolled in the clinical trials used to evaluate efficacy of the drug VRAYLAR.  In total, 1360 men (72%) and 541 women (28%) participated in the clinical trials used to evaluate efficacy of the drug VRAYLAR.

Source: Company Trial Data

The figure and table below summarize the percentage of patients by race who participated in the clinical trials.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the VRAYLAR clinical trial. In total, 811 White (43%), 655 Black (35%), 328 Asian (17%), 6 American Indian or Alaska Native (<1%), 7 Native Hawaiian or Other Pacific Islander (<1%), 48 identified as Other (3%), and 46 were not able to be identified (2%).

<1%=less than 1%
* Not collected in some countries per local regulations
Source: Company Trial data

Table 1. Baseline Demographics by Race

RaceNumber of PatientsPercentage of Patients
White81143%
Black or African American65535%
Asian32817%
American Indian or Alaska Native6less than 1%
Native Hawaiian or Other Pacific Islander7less than 1%
Other483%
Not collected*462%

* Not collected in some countries per local regulations
Source: Company Trial Data

The figure below summarizes the percentage of patients by age group enrolled in the clinical trials.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the VRAYLAR clinical trial.  In total, 1900 were between 18 and 64 years (100%) and 1 was 65 years and older (<1%).

<1%=less than 1%
Source: Company Trial Data

Who participated in the trials?

The table below summarizes baseline demographics for the Safety population. Overall demographics for the efficacy population were similar.

Table 5. Baseline Demographics for the Trials

Demographic ParametersVRAYLAR
1.5-3 mg
(N=539)
n (%)
VRAYLAR
4.5-6 mg
(N=575)
n (%)
VRAYLAR
9-12 mg†
(N=203)
n (%)
Placebo

(N=584)
n (%)
Total

(N=1901)
n (%)
Sex
Male372 (69)422 (73)151 (74)415 (71)1360 (72)
Female167 (31)153 (27)52 (26)169 (29)541 (28)
Age
Mean years (SD)37 (10)38 (11)40 (10)37.8 (11)37.8 (11)
Median (years)3637413837
Min, Max (years)18, 6118, 6518, 6318, 6418, 65
Age Group
=18 - <65 years539 (100)574 (100)203 (100)584 (100)1900 (100)
>=65 years01(<1)001 (<1)
Race
White278 (52)24749 (24)237 (41)811 (43)
Black or African American141 (26)191108 (53)215 (37)655 (35)
Asian90 (17)10438 (19)96 (16)328 (17)
American Indian or Alaska  Native3 (1)102 (<1)6 (<1)
Native Hawaiian or Other Pacific Islander1 (<1)11 (1)4 (1)7 (<1)
Other9 (2)147 (3)18 (3)48 (3)
Not collected17 (3)17012 (2)46 (2)
Ethnicity
Hispanic or Latino33 (6)41 (7)20 (10)42 (7)136 (7)
Not Hispanic or Latino487 (90)515 (90)183 (90)529 (91)1714 (90)
Not collected19 (4)19 (3)013 (2)51 (3)
Region
United States228 (42)302 (53)162 (80)318 (55)1010 (53)
South America12 (2)13 (2)6 (3)16 (3)47 (2)
Europe212 (39)157 (27)0155 (26)524 (28)
Asia87 (16)100 (17)35 (17)93 (16)315 (17)
Africa03 (1)02 (<1)5 (<1)

The maximum approved dose is 6 mg/day
Source: Company Trial Data

How were the trials designed?

Three trials evaluated the benefit of VRAYLAR, and two of them evaluated the side effects.

In the trials, patients were randomly assigned to receive either VRAYLAR or placebo. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.

The trials measured symptoms of schizophrenia.

How were the trials designed?

VRAYLAR was studied in three 6-week, randomized, double-blind, placebo controlled, trials in adult patients with schizophrenia who met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, (DSM IV TR) criteria. An active control arm (risperidone or aripiprazole) was included in two trials to assess assay sensitivity.

VRAYLAR or placebo was administered daily.

The primary endpoint was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score.

The PANSS is a 30-item scale that measures positive symptoms of schizophrenia (7 items), negative symptoms of schizophrenia (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); the total PANSS scores range from 30 to 210.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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Page Last Updated: 05/09/2017
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