e suspension based on mg/m2 body surface area, respectively.
14 CLINICAL STUDIES
Efficacy for PERSERIS was demonstrated in an 8-week, randomized, double-blind, placebo-controlled study (Study 1, NCT #02109562). The study eva luated the efficacy, safety and tolerability of PERSERIS (90 and 120 mg subcutaneous every 4 weeks) compared with placebo in adults (age 18 to 55 years, inclusive) experiencing acute exacerbations of schizophrenia. Patients were required to have a Positive and Negative Syndrome Scale (PANSS) total score of 80 to 120 inclusive (moderate to severely ill) at the screening visit, occurring 3 to 8 days before the start of double-blind treatment, without an improvement in the PANSS total score of ≥ 20% between screening and the first dosing day.
At the screening visit, all patients received two doses of 0.25 mg oral risperidone 24 hours apart to establish tolerability. Patients were then placed in an inpatient setting, if not already hospitalized, and tapered off their current oral antipsychotic medication (if they were taking one) over a period of 3 to 8 days. Patients were randomized to receive 2 doses of subcutaneous PERSERIS (90 mg or 120 mg) or placebo 28 days apart (on Day 1 and Day 29). No supplemental oral risperidone was permitted during the study.
The primary endpoint was the change in PANSS total score from baseline to end of study (Day 57). Both PERSERIS 90 and 120 mg doses demonstrated a statistically significant improvement compared with placebo based on the primary endpoint (TABLE 8). The results at each scheduled visit are displayed in FIGURE 14.
Characteristics of the patient population were balanced across the treatment groups. The mean baseline PANSS total score ranged from 94 to 96 across the groups. Most patients were male (74 to 83% per group), and the mean ages were 40 to 43 in each group. Most patients in this study were black or African American (71 to 75% per group). Of the 354 subjects randomized to treatment, 337 were included in the intent-to-treat (ITT) population, and 259 (73%) completed the study.
Subgroup analyses by gender, age, and race did not suggest any clear evidence of differential responsiveness to PERSERIS.
Table 8: Primary Efficacy Analysis Results for Study 1
ITT: intent-to-treat; SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval
ªDifference (drug minus placebo) in least-squares mean change from baseline
*Doses that are statistically significantly superior to placebo
Primary Efficacy Measure: PANSS
Treatment Group
N
(# ITT subjects) Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted
Differencea (95% CI)
PERSERIS 90 mg* 111 95.5 (9.23) -19.86 (1.56) -6.50 (-10.87, -2.13)*
PERSERIS 120 mg* 114 94.9 (8.09) -23.61 (1.58) -10.24 (-14.64, -5.85)*
Placebo 112 94.1 (8.89) -13.37 (1.58) --
Figure 14. Least Square Mean Change from Baseline (+/- Standard Error) in PANSS Total Scores by Days
Figure 14
The secondary efficacy endpoint was defined as the CGI-S score at Day 57. Both PERSERIS treatment groups demonstrated statistically significantly better CGI-S scores versus placebo.
16 HOW SUPPLIED/STORAGE AND HANDLING
PERSERIS (risperidone) for extended-release injectable suspension, for subcutaneous use is, when fully mixed, a viscous suspension that varies from wh |
