Safety and Pharmacokinetic Profile of a 2-Month Dose Regimen of Aripiprazole Lauroxil: A 44-Week Phase 1 Study and Subsequent Population Pharmacokinetic Modeling

December 21, 2017

This poster was presented at the 30th annual  Psych Congress, held Sept. 16-19, 2017, in New Orleans, Louisiana.

Introduction: Aripiprazole lauroxil (AL) is an FDA-approved, long-acting injectable antipsychotic for the treatment of schizophrenia. A phase 1, 44-week, open-label study evaluated safety, tolerability, and pharmacokinetics (PK) of AL (1064mg) with a dose interval of every 8 weeks (q8wk) (ClinicalTrials.gov: NCT02320032) and was used to inform a 2-month population PK (2MPopPK) model for FDA approval.

Methods: Patients with schizophrenia (N=139) were randomized to one of three AL regimens: 441mg every 4 weeks (q4wk), 882mg every 6 weeks (q6wk), or 1064mg q8wk (totaling 7, 5, or 4 intramuscular injections over 24 weeks, respectively). Patients continued on maintenance oral antipsychotics. Safety and PK assessments occurred during the 24-week study period, and for an additional 20 weeks of follow-up after the last AL injection. Data were combined with data from four prior studies to develop the 2MPopPK model (N=700).

Results: The safety profile of AL 1064mg q8wk was comparable with 882mg q6wk and 441mg q4wk. The most common adverse event was injection-site pain. Administration of AL 1064mg q8wk provided continuous exposure to aripiprazole and yielded aripiprazole concentrations that were within the range associated with the clinical efficacy and tolerability of currently approved AL. The 2MPopPK model showed that median steady-state concentrations of aripiprazole for 1064mg q8wk were comparable with the 882mg q6wk and 662mg q4wk regimens.

Conclusions: The safety profile of AL 1064mg q8wk was consistent with currently approved regimens. The 1064mg q8wk dosage resulted in aripiprazole concentrations within the established AL therapeutic window and was recently approved as a 2-month dose regimen.

Authors: 
Peter J Weiden, MD; Marjie L Hard, PhD; Angela Wehr, PhD; Lisa von Moltke, MD
Sponsoring Organization: 
Alkermes, Inc.
Year: 
2017
Tracks: 
Schizophrenia