Pharmacokinetic Evaluation of a 1-Day Treatment Initiation Option for Starting Long-Acting Aripiprazole Lauroxil for Schizophrenia

Abstract

Supplemental digital content is available in the text.

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“…Importantly, plasma aripiprazole levels observed for the 1-day regimen in this study fell within the range of levels associated with significant improvement in schizophrenia symptoms in the pivotal AL 12-week efficacy study. 4,19 The safety profile of the 1-day initiation regimen was comparable to that of the 21-day initiation regimen and consistent with the known safety profile of aripiprazole and AL. 19 AE rates were similar between patients in the 1-and 21-day initiation regimens (Supplemental Table 3).…”

“…4,19 The safety profile of the 1-day initiation regimen was comparable to that of the 21-day initiation regimen and consistent with the known safety profile of aripiprazole and AL. 19 AE rates were similar between patients in the 1-and 21-day initiation regimens (Supplemental Table 3). The incidence of akathisia, an AE associated with oral aripiprazole treatment, 20 was relatively low (5% for the 1-day initiation regimen and 2.5% for the 21-day initiation regimen).…”

“…The comparison between initiation regimens demonstrates that the 1-day initiation regimen of AL NCD þ a single 30 mg dose of oral aripiprazole results in rapid achievement of plasma aripiprazole levels comparable to the 21-day 15 mg/day oral aripiprazole initiation regimen and that aripiprazole levels persist through the first month after treatment initiation. Total aripiprazole exposure (the area under the curve) was also similar for the 1-and 21-day initiation regimen groups 19 (Supplemental Figure 2 and Table 2). Moreover, the two initiation regimens were noted to have comparable peak aripiprazole exposures (Supplemental Figure 3 and Table 2).…”

“…To determine whether the 1-day initiation regimen is comparable to the 21-day regimen, a phase 1, doubleblind, placebo-controlled study in adult patients with schizophrenia initiating AL therapy was carried out to assess the kinetics, safety, and tolerability of the two regimens. 19 The four-arm study compared the 1-and 21-day AL initiation regimens for two individual AL doses (441 or 882 mg administered monthly) as illustrated in Supplemental Figure 1. Patients assigned to the 1-day initiation regimen received a single AL NCD injection given intramuscularly and a single 30 mg dose of oral aripiprazole administered together on day 1 and then received an oral placebo on days 2-21.…”

“…Their baseline demographic and clinical characteristics are shown in Supplemental Table 1. 19 Figure 4 shows study patients' mean plasma aripiprazole levels for 28 days after administration of the 1-day vs. 21-day AL initiation regimens and first AL dose (Figure 4(a), AL 441 mg groups; Figure 4(b), AL 882 mg groups). The comparison between initiation regimens demonstrates that the 1-day initiation regimen of AL NCD þ a single 30 mg dose of oral aripiprazole results in rapid achievement of plasma aripiprazole levels comparable to the 21-day 15 mg/day oral aripiprazole initiation regimen and that aripiprazole levels persist through the first month after treatment initiation.…”