Development of an Ondansetron Transdermal Patch for Pregnancy-Induced Nausea and Vomiting

Pregnancy-induced nausea and vomiting (PINV) afflicts 50-85% of all pregnancies, of which there are 4 million each year in the US alone. Symptoms, often disabling and sometimes severe and unremitting, occur in 80% of sufferers at random times throughout the day, and typically persist throughout the first and early second trimester, and occasionally much longer. Currently available treatments, of which only one is FDA-approved, require oral ingestion and retention of medication multiple times daily, which can be challenging in the face of unrelenting nausea or vomiting. The proposed SBIR Phase I project aims to complete the pharmaceutical development of a transdermal dosage form designed to deliver the 5-HT3 antagonist anti-nauseant ondansetron to treat pregnancy-induced nausea and vomiting (PINV). The final product will be a small patch which is applied once or twice weekly. Following an initial lag period on the first day of dosing, the product will deliver therapeutic quantities of drug continually throughout the period of application without the need for oral administration. Our product is intended to provide a safe, effective, and tolerable outpatient treatment for PINV that avoids the oral route of administration entirely. It is based on a proprietary skin penetration enhancement system which increases ondansetron absorption through the skin by 450-fold over unenhanced formulations. In a pre-IND meeting, we have obtained FDA’s guidance on the path to regulatory approval. Once approved, this novel product will present a cost-effective, convenient alternative to pregnant women suffering with PINV. The aims of this proposed SBIR Phase I program for a transdermal ondansetron product are to: 1) complete optimization of product design, 2) produce pilot scale patches which conform to product specifications, and 3) conduct IND-enabling dermal safety studies. Upon successful completion of this program, an SBIR Phase II follow-up program will be proposed that will include filing an IND, scale-up and manufacturing of clinical suppllies, and conducting a clinical pharmacokinetics proof-of-concept study in healthy volunteers, while in parallel performing a repeat-dose dermal toxicity study in minipigs to support longer-term clinical studies in pregnant women.