Feasibility of a Risperidone Implant for the Maintenance Treatment of Schizophrenia for up to 12 Months After a Single Administration

Abstract

Introduction

Disruptions of antipsychotic therapy lead to greater symptoms and increased likelihood of relapse. One way to improve medication adherence has been with long-acting formulations, usually administered by injection. Implantable technology has been used to support medication continuity in a few therapeutic areas, e.g., contraception. Despite the potential benefits from implants, this modality is not yet available for maintenance treatment of schizophrenia. Delpor, Inc. is developing an investigational risperidone implant (DLP-114) that releases therapeutic drug levels for up to 12-months. Initial clinical findings are reported below.

Methods

The DLP-114 implant is a titanium cylinder approximately 4-5 cm long and 5 mm in diameter. It has membranes mounted on each end and is loaded with a proprietary formulation of risperidone.

The clinical study (NCT04418466) was an open-label study in stable schizophrenia patients to evaluate the safety, tolerability, and pharmacokinetics (PK) of switching from oral risperidone to DLP-114. Schizophrenia patients (N=28), stable on a 2-3 mg dose of oral risperidone for ≥2 weeks were randomized to receive either 6- or 12-month DLP-114 implant devices. Each patient received two DLP-114 devices implanted in the abdomen. Device placements were conducted through a 10-minute procedure using local anesthetic and a custom placement tool. Plasma levels of risperidone and 9-hydroxyrisperidone were tracked over the treatment period, and patients were clinically monitored for signs of relapse. Patient safety (including local tolerance and emergent AEs) and PK were the principal endpoints. Secondary clinical endpoints included PANSS and CGI scores.

Results

The placement and removal procedures were well tolerated. Of 28 enrolled patients, two were lost to follow up and one asked to have the implant removed prior to the end of the dosing period. One nonrelated SAE (pulmonary embolism) was reported. Treatment-related AEs were generally mild, and included implant site pain/soreness/tenderness, drowsiness, ecchymosis, increased appetite, insomnia, and headache. The PK profile in both groups followed near zero-order kinetics with both dosing periods until the end of study. The average steady-state plasma concentration ranged between 7-13 ng/mL. One patient was removed from the study with signs of impending relapse. All other patients were clinically stable for the study duration, with average PANSS scores from 50-60 and CGI-I scores from 3-4. PANSS and CGI-I scores were comparable between the oral and the implant phases of the study.

Conclusions

DLP-114 was well tolerated for up to 12 months. Average PANSS and CGI-I scores were similar between the oral and implant treatment phases, suggesting that, for most patients, DLP-114 provided a comparable therapeutic benefit to 2-3 mg of daily oral risperidone over time. Plasma concentrations of risperidone and 9-hydroxyrisperidone were substantially constant for 6-12 months, but values for steady-state Cave fell slightly below the target of 10-14 ng/mL.

Funding

Research reported in this poster was supported by Delpor, Inc. and by the National Institute of Mental Health of the National Institutes of Health under award number R44MH094036.