Phase II year
2013
(last award dollars: 2020)
Phase II Amount
$9,046,698
The objective of the proposed study is to develop a subcutaneous implant of risperidone which provides consistent therapeutic blood levels of the drug for 3 months. The benefits of such product include improved medication adherence, the ability to withdraw the medication if needed due to treatment emergent Adverse Effects (AEs), fewer relapses, and improved efficacy. Atypical antipsychotics have been used for several years with great results for the treatment of schizophrenia. However, the effectiveness of these agents in maintenance treatment is limited due to patient non-adherence. Lack of medication adherence has been shown to highly correlate with relapse and re-hospitalization. With each successive relapse, the patient's long- term prognosis deteriorates and previous level of functioning is rarely achieved. Patient non-adherence also places an additional burden on the US healthcare system, which is estimated at $2.3 Billion per year. The proposed formulation of risperidone will be delivered through a small subcutaneous reservoir, which can be implanted during a simple, 15 minute, in-office procedure. Although some subcutaneous implant technologies already exist, none of them is suitable for the delivery of risperidone or other antipsychotics. Results of recent studies show that 86% of physicians and 50% of patients support the use of implants in this disease area. Delpor received Phase I support for this project last year with the objective to complete the preclinical proof-of- concept (defined as a PK and local tolerance study). All Phase I Aims have now been successfully completed and Delpor has demonstrated that the technology is capable of delivering the drug in a zero-order fashion and can maintain steady plasma levels with minimal variability for over 3 months. Furthermore, the local safety of the device has now been shown in animals. The next major milestone, as the company approaches commercialization, is to complete the clinical proof-of-concept which is defined again as PK and local tolerance. The proposed study will allow the company to assemble and file the IND as well as validate all the necessary QA/QC methods in order to achieve such milestone. After the clinical validation of the technology, the product will be very attractive to investors and partners as it will be closer to approval and further de-risked. The clinical benefits of long-acting antipsychotic formulations have already been proven with depot formulations. Relative to daily oral therapy, a 2-week injectable depot formulation of risperidone is associated with improved treatment adherence, improvement in clinical symptoms, and greater reduction in hospital stays in patients with schizophrenia. However, two critical barriers have impeded the development of longer acting depot formulations: Safety issues since the drug cannot be withdrawn after administration, and technical limits of depot technology to provide consistent blood levels for more than 2-4 weeks. The proposed program is designed to address these problems and provide multiple benefits over existing depots including extending the release to 3 months, offering the ability to withdraw the medication, and achieving a safer PK profile.
Public Health Relevance Statement: Public Health Relevance: Patient non-adherence in schizophrenia is estimated at 24%-74% of patients and accounts for approximately 40% of all relapses. Compared to existing schizophrenia treatment alternatives, the proposed product will reduce relapses during maintenance treatment, improve safety, and increase overall treatment success. The final outcome will be an improvement in patient lives, and a reduction in overall healthcare costs.
NIH Spending Category: Bioengineering; Brain Disorders; Mental Health; Patient Safety; Schizophrenia
Project Terms: Accounting; Acids; Address; Adherence (attribute); Adoption; Adverse effects; Adverse event; alternative treatment; analytical method; Animals; Antipsychotic Agents; Area; assay development; atypical antipsychotic; Automobile Driving; base; Biological Assay; Blood; Blood drug level result; Clinical; Clinical Protocols; commercialization; design; Development; Device Designs; Devices; Diffusion; Disease; Dose; Drug Formulations; Drug Kinetics; Effectiveness; Equation; Equilibrium; Exhibits; Health Care Costs; Healthcare Systems; Hospitalization; Hydrolysis; Implant; implantation; Implantation procedure; improved; In Vitro; Injectable; Injection of therapeutic agent; Lactic acid; Length of Stay; Maintenance; manufacturing process; medication compliance; method development; Methods; Oral; Outcome; outcome forecast; Patient Noncompliance; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Phase I Clinical Trials; Physicians; Plasma; Polymers; pre-clinical; Procedures; Process; programs; Protocols documentation; prototype; public health relevance; Relapse; Relative (related person); Reporting; Research Personnel; research study; response; Risk; Risperidone; Safety; safety study; Sampling; scale up; Schizophrenia; Site; Sterilization; subcutaneous; success; Symptoms; System; Technology; technology validation; Testing; Therapeutic; Time; tool; treatment adherence; Uncertainty; Validation
