Extended-release risperidone capsule may improve drug adherence in schizophrenia

An oral, ultra-long-acting, extended-release risperidone capsule provided sustained therapeutic levels of risperidone over 1-week dosing intervals, according to results of a randomized, parallel group, placebo-controlled study.

A researcher presented the study findings at the American Society for Clinical Psychopharmacology annual meeting.

“Preventing relapse is critical in reducing health care costs and preserving function in individuals with schizophrenia,” David Walling, PhD, chief clinical officer at Apex Innovative Sciences and chief executive officer and principal investigator of Collaborative Neuroscience Research, told Healio Psychiatry. “In the U.S. alone, medication nonadherence causes at least 10% of hospitalizations and approximately 125,000 avoidable deaths per year, costing the health care system more than most other diseases. LYN-005 is Lyndra’s oral, ultra-long-acting, extended-release risperidone capsule, in development for the weekly treatment of schizophrenia, and it is designed to provide consistent drug levels for an entire week or as long as 1 month from one, normal-sized capsule, which is something no oral therapy has ever achieved.”

In the current study, Walling and colleagues enrolled 32 clinically stable patients who had a primary diagnosis of schizophrenia or schizoaffective disorder. Patients received immediate-release 2 mg or 4 mg risperidone tablets according to their current antipsychotic dose for 13 days, after which the researchers randomly assigned them 3:1 to receive immediate-release risperidone-matched placebo and LYN-005 (14 mg or 28 mg risperidone; 12 patients per group) or LYN-005-matched placebo and immediate-release risperidone (2 mg or 4 mg; four patients per group) for 3 weeks. They received LYN-005 once weekly for a total of three doses, and immediate-release risperidone administration occurred once daily. Treatment assignments were blinded, but dose levels were not. Pharmacokinetics after LYN-005 capsules and after immediate-release risperidone, and the incidence of adverse events, served as primary endpoints. Pharmacokinetics after switching from immediate-release risperidone to LYN-005 served as the secondary endpoint. The researchers used a non-compartmental model to conduct pharmacokinetics analyses.

Results showed an increase in systemic exposure to risperidone active moiety with increasing dose following LYN-005 administration. The researchers observed exposure throughout the dosing intervals and noted peak concentration and generally observed peak concentration within the first 3 days of dosing. LYN-005 peak exposure appeared lower than those associated with immediate-release risperidone. Steady-state appeared to be achieved before the LYN-005 dose, based on inspection of pre-dose concentrations. Approximately 85% of patients completed all three dosages, suggesting LYN-005 was well tolerated. Patients reported no severe or serious adverse events. A total of 75% of patients in LYN-005 groups reported adverse events, 10 of which occurred in the 14 mg group and eight in the 28 mg group. A total of eight patients had a moderate adverse event. Gastrointestinal disorders represented the most common adverse events, occurring among 54% of patients, with a higher incidence among the 28 mg group compared with the 14 mg group. A total of nine patients reported abdominal pain, discomfort and/or tenderness, and five reported nausea. Overall, LYN-005 had a higher incidence of adverse events than immediate-release risperidone; however, the adverse events were considered mild and transitory, with fewer reported with subsequent LYN-005 dosing. Adverse events occurred among two patients in immediate-release risperidone groups; one patient had alanine aminotransferase and weight increases, and one had diarrhea and akathisia.

“These data are very promising as, in addition to possibly improving adherence, weekly oral risperidone treatment may provide more consistent plasma drug levels than daily dosing,” Walling said. “This investigational product in development, LYN-005, has the potential to improve drug compliance and adherence for people with schizophrenia or schizoaffective disorder by reducing the number of capsules needed for antipsychotic treatment to one per week.”