Two 6-week, pivotal trials evaluated efficacy and safety in patients with schizophrenia who would benefit from hospitalization
REXULTI pivotal trial design1-3:
- Two 6-week, randomized, placebo-controlled, fixed-dose pivotal trials
- Patients who met DSM-IV-TR criteria for SZ and would benefit from hospitalization or continued hospitalization for an acute exacerbation of symptoms
- In Study 3, patients were randomized to receive 2 or 4 mg of REXULTI or placebo, while in Study 4 patients received 1, 2 or 4 mg of REXULTI
- Treatment initiated at 1 mg/day on Days 1–4, titrated to 2 mg/day on Days 5–7, then maintained or increased to 4 mg/day on Day 8, depending on treatment arm
- Primary endpoint was change in total PANSS score from baseline to 6 weeks
Patient demographic
Average baseline PANSS total score: moderately to markedly ill
Study 3 and Study 4: REXULTI—mean baseline PANSS total score at randomization1,3-5,a
The PANSS is a 30-item scale that measures positive symptoms of SZ (7 items), negative symptoms of SZ (7 items), and general psychopathology (16 items), each rated on a scale 1 (absent) to 7 (extreme); the total PANSS scores range from 30 (best) to 210 (worst).
aPatients were hospitalized for screening and throughout the 6-week treatment phase.1
bMean baseline PANSS total scores (SD) for patients were—Study 3: REXULTI 2 mg/day, 95.9 (13.8); REXULTI 4 mg/day, 94.7 (12.1); placebo, 95.7 (11.5); Study 4: REXULTI 2 mg/day, 96.3 (12.9); REXULTI 4 mg/day, 95.0 (12.4); placebo, 94.6 (12.8).1
cn=358; sum of patients in the efficacy analyses who received placebo in Study 3 and Study 4.1
dn=718; sum of patients in the efficacy analyses who received REXULTI 2 mg/day or 4 mg/day in Study 3 and Study 4.1
DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision); PANSS, Positive and Negative Syndrome Scale; SD, standard deviation.
Short-term data: Significantly superior efficacy at 4 mg in two 6-week trials
Study 3 and Study 4: REXULTI 4 mg/day—reduction
in PANSS total score vs placebo in pooled data at 6 weeks1,6
ep<0.0001 vs placebo.2
Adapted with permission.
Difference in mean reduction in PANSS total score vs placebo at Week 6 in both pivotal trials
Study 31,2
| REXULTI 2 mg/day | REXULTI 4 mg/day |
| -8.7 (95% CI: -13.1, -4.4), p<0.0001 | -7.6 (95% CI: -12.0, -3.1), p=0.0006 |
Study 41,3
| REXULTI 2 mg/day | REXULTI 4 mg/day |
| -3.1 (95% CI: -7.2, 1.1), p=0.1448 | -6.5 (95% CI: -10.6, -2.4), p=0.0022 |
- Statistical significance was achieved at 2 mg/day vs placebo in Study 31
- A 1-mg/day treatment arm was included in Study 4. Statistical significance was not achieved for the primary endpoint with either the 1-mg/day dose or the 2-mg/day dose compared with placebo (p>0.05)2
The PANSS is a 30-item scale that measures positive symptoms of SZ (7 items), negative symptoms of SZ (7 items), and general psychopathology (16 items), with each rated on a scale of 1 (absent) to 7 (extreme); the total PANSS scores range from 30 (best) to 210 (worst).
CI, confidence interval; LS, least squares; PANSS, Positive and Negative Syndrome Scale; SE, standard error.
Contraindication
In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.
Maintenance withdrawal trial evaluated impending relapse after stabilization
REXULTI randomized withdrawal trial design1:
- Stabilization phase (single-blind): patients with SZ were stabilized on flexible doses of REXULTI 1 mg/day to 4 mg/day for at least 12 weeks (n=202)
- Maintenance phase (double-blind): patients who met stabilization criteria were then randomized to either their achieved stable dose of REXULTI 1 mg/day to 4 mg/day (n=97) or placebo (n=105) for 52 weeksf
- Primary endpoint was time from randomization to impending relapse in the maintenance phase
- Impending relapse was defined as any of the following:
- CGI-improvement score of ≥5 and an increase to >4 on PANSS conceptual disorganization, hallucinatory behavior, suspiciousness, or unusual thought content, with either a ≥2 increase on a specific item or ≥4 increase on the combined 4 items
- Hospitalization due to worsening of psychotic symptoms
- Current suicidal behavior
- Violent/aggressive behavior
- Impending relapse was defined as any of the following:
Study 5: REXULTI—PANSS total score during stabilization
and maintenance phases for REXULTI 1 mg/day to 4 mg/day and placebo7,8
Single-blind stabilization
- Flexible dose
- Visits every week for 4 weeks, every other week thereafter for up to 36 weeks
Double-blind maintenance
- Fixed dose achieved in the stabilization phase
- Visits every other week for 8 weeks, every 4 weeks thereafter for up to 52 weeks
Mean dose during maintenance phase was 3.6 mg/day.7
PANSS total mean baseline scores [SD] (at Week zero in the maintenance phase): REXULTI 1 mg/day to 4 mg/day (n=97), 56.5 [8.7]; placebo (n=105), 58.1 [8.1].7
Patients had a PANSS total score of >80 and, if needed, were part of a 1- to 4-week washout phase of previous medications before moving on to stabilization.
fStabilization was defined as all of the following: (1) outpatient status; (2) PANSS total score ≤70; (3) a PANSS score of ≤4 on conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content; (4) CGI-Severity ≤4; (5) no current suicidal behavior; (6) no violent or aggressive behavior resulting in injury or property damage.7
The PANSS is a 30-item scale that measures positive symptoms of SZ (7 items), negative symptoms of SZ (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 (best) to 210 (worst).
CGI, Clinical Global Impressions; PANSS, Positive and Negative Syndrome Scale; SD, standard deviation.
Important Warning and Precaution for Cerebrovascular Adverse Events, Including Stroke
In clinical trials, elderly patients with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis.
Demonstrated efficacy as maintenance treatment
Study 5: REXULTI—Kaplan-Meier estimation of
patients with impending relapse in the maintenance phase1,7
gOf the 202 patients randomized, 2 patients were excluded from the efficacy analysis: 1 patient taking REXULTI did not have post-randomization efficacy evaluations, and 1 patient taking placebo did not take the investigational medicinal product.1
hCox proportional hazards model with treatment as term.7
iLog-rank test.7
Maintenance phase efficacy sample. Kaplan-Meier curves of the cumulative proportion of patients meeting criteria for impending relapse during the double-blind treatment phase vs placebo.1
- Trial was terminated early because maintenance of efficacy had been demonstrated1
CI, confidence interval; HR, hazard ratio.
Important Warning and Precaution for Neuroleptic Malignant Syndrome (NMS)
NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of REXULTI, intensive symptomatic treatment, and monitoring.
Examine the safety profile for REXULTI.
Learn about once-daily treatment with a target dose of 2 mg–4 mg.1