Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation

Abstract

Aripiprazole lauroxil (AL), a new long-acting injectable antipsychotic, demonstrated safety and efficacy in treating acute exacerbation symptoms of schizophrenia in a 12-week placebo-controlled trial of two doses of AL (441 mg and 882 mg) administered every 4 weeks. We performed a post hoc analysis of this trial to evaluate the efficacy of AL in the subgroup of patients with severe psychotic symptoms, defined as those with baseline Positive and Negative Syndrome Scale (PANSS) Total score above the median score of 92 (n = 309). Change from baseline to Day 85 in PANSS Total score; Positive, Negative, and General Psychopathology subscale scores; and overall response rate were assessed. Statistically significant and clinically meaningful improvements in PANSS Total score were demonstrated with AL 441 mg and AL 882 mg, with placebo-adjusted differences of −14.7 (p b 0.0001) and −16.6 (p b 0.0001), respectively. Significant and clinically meaningful findings with both doses of AL were also demonstrated for the PANSS subscales and responder rates. Overall responder rates at Day 85 were significantly greater for AL 441 mg (49%; p b 0.001) and 882 mg (61%; p b 0.001) groups vs. placebo (18%). Common adverse events (N 5%) were schizophrenia, akathisia, headache, insomnia, and anxiety. AL demonstrated robust efficacy in treatment of the subgroup of patients experiencing severe psychotic symptoms. Both doses (441 mg and 882 mg) were effective, with numerically greater improvement in symptoms and proportion of responders favoring the higher dose arm. Both doses had a side effect profile consistent with the known safety profile of aripiprazole.

Pharmacokinetic Profile of a 2-Month Dose Regimen of Aripiprazole Lauroxil: A Phase I Study and a Population Pharmacokinetic Model

“…Aripiprazole lauroxil (AL) is an intramuscular injectable extended-release prodrug of aripiprazole that is approved for the treatment of schizophrenia [ 5 , 6 ]. Pivotal clinical studies have demonstrated that AL 441 mg and 882 mg doses administered monthly (every 4 weeks [q4wk]) are efficacious [ 7 , 8 ] and population pharmacokinetic (PopPK) modeling provided the pharmacokinetic basis for the approval of the 662 mg dose q4wk and the 882 mg dose every 6 weeks (q6wk) [ 9 ].…”

Long-Acting Injectable Antipsychotics and Infections in Schizophrenia

“…Three studies reported that the placebo was intralipid (fat emulsion for human use). 19,21,22 The remaining studies did not describe the composition of the placebo. In all studies combined, the prevalence of any infection was 2.4% in the LAI antipsychotic group and 1.5% in the placebo group (Table 2).…”

“…Mean study duration was 13 weeks, mean subject age was 39.5, mean % male was 71.5%, mean BMI was 27.3, and mean PANSS total score was 86.8. Three studies reported that the placebo was intralipid (fat emulsion for human use) 19,21,22 . The remaining studies did not describe the composition of the placebo.…”

An Integrated Pharmacokinetic–Pharmacodynamic–Pharmacoeconomic Modeling Method to Evaluate Treatments for Adults with Schizophrenia

“…Patients who recovered from their relapse moved to the “remission” health state. From all health states, patients could move to the absorbing health state “death.” Adverse events were not modeled because evidence regarding adverse events at different C min was unavailable and evidence also suggested that the safety profiles of AM and AL were similar [ 20 , 21 ]. The model had a cycle length of 2 weeks, which was the highest common denominator of the 4-, 6-, and 8-week regimens of the evaluated LAIs, was built in R version 4.0.2 [ 1 ], and made use of the RxODE package [ 2 ].…”