David P. Walling
NEW YORK — Phase 1 data demonstrated a nano-crystalline milled dispersion of aripiprazole lauroxil, an investigational product designed for initiation onto Aristada, was well-tolerated when combined with 30-mg oral aripiprazole as part of a 1-day initiation regimen, according to a Alkermes press release. Data will be presented in a poster here.
Currently under review by the FDA, Aripiprazole Lauroxil Nano-Crystal Dispersion may present an alternative to the 21-day initiation period required before beginning long-term Aristada (aripiprazole lauroxil, Alkermes) therapy for the treatment of schizophrenia if approved.
“Many patients with schizophrenia, particularly those in an acute episode, have difficulty remembering to take their medications as prescribed. Currently, to start many of our long-acting medications, you need to supplement with oral medications for the first few days,” study author David P. Walling, PhD, chief executive and clinical officer at Collaborative Neuroscience Network Inc., told Healio Psychiatry. “The 1-day regimen that we studied makes it much easier in that subjects can receive an additional injection and one oral pill and get the needed drug levels quickly.”
Currently, the first aripiprazole lauroxil dose requires 21 days of supplementation with oral aripiprazole, according to the investigators; however, a nano-crystalline milled dispersion of aripiprazole lauroxil (ALNCD) has been developed as a 1-day initiation regimen to allow for faster dissolution. This dissolution should yield rapid achievement of therapeutic levels of aripiprazole when ALNCD is given with the first Aristada dose.
In this blinded, randomized, phase 1, pharmacokinetic, safety and tolerability study, Walling and colleagues compared the 1-day initiation regimen for starting long-term Aristada therapy with a 21-day oral aripiprazole regimen. They hypothesized that combining a single injection of ALNCD and a single 30-mg dose of oral aripiprazole within the 1-day initiation regimen would attain concentrations of aripiprazole comparable with those seen within the 21-day oral regimen. Participants were randomly assigned to receive the 1-day initiation regimen or the 21-day initiation regimen (15 mg/day oral aripiprazole), along with a dose of Aristada 441 mg or 882 mg.
Overall, 133 patients completed the study. Walling and colleagues found the 1-day initiation regimen groups had aripiprazole exposure comparable to all corresponding 21-day initiation regimen groups. The results indicated that the combination of ALNCD and 30-mg oral aripiprazole as part of a 1-day initiation regimen with Aristada was well-tolerated and a suitable alternative to 21 days of aripiprazole.
“The 1-day regimen is particularly important because it allows clinicians to start patients on a long-acting injectable without the need to supplement with oral medications for 3 weeks,” Walling told Healio Psychiatry.
The most common adverse events were injection-site pain, headache, increased weight, insomnia, dyspepsia and anxiety. Though nine akathisia events occurred, eight were mild and none led to discontinuation; specifically, four events occurred in four 1-day regimen patients and five events in two 21-day regimen patients, according to the poster.
“The take home for clinicians is that it is possible to simplify the initiation of a long-acting injectable, in this case aripiprazole lauroxil, by utilizing the 1-day regimen that we studied,” Walling said. “This makes it easier for patients, caregivers and clinicians because you know the subject is getting the needed medications at the time that you start them on the medication.” – by Savannah Demko
Walling D, et al. Poster #142. Presented at: American Psychiatric Association Annual Meeting; May 5-9, 20178; New York.
Disclosures: Walling was a principal investigator of the study. He is also an employee of CNS Network, Inc. and reports consulting for Acadia Pharmaceuticals, Janssen and Otsuka Pharmaceuticals.
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