Development of Zindol® through multi-center clinical trial for chemotherapy induced nausea and vomiting

Abstract

Despite the widespread use of 5-HT3 receptor antagonist anti-emetics, chemotherapy induced nausea and vomiting (CINV) continues to be reported by up to 70% of adult patients and up to 58% of children receiving highly emetogenic chemotherapy agents. Nausea and vomiting are among the most distressing side effects of chemotherapy. Zindol® is an enhanced ginger product that is standardized by the bioactive constituents, gingerols and shogaols, of ginger (Zingiber officinale Roscoe). We utilized polarity-guided supercritical fluid fractionation SFS-CXF technology to establish conditions for the isolation of the active ingredients and then manufactured the API using SFS-CXP following cGMP. The API was then formulated to achieve a specific concentration of gingerols and shogaols with all-natural liquid excipients designed to maximize the stability and bioavailability of the bioactive constituents and encapsulated into gel capsules with a nitrogen head following cGMP. Zindol® was successfully evaluated in a multi-center, 644-patient, dose-finding, placebo-controlled, randomized Phase II/III clinical trial as an adjunctive therapy to conventional 5-HT3 anti-emetics for nausea in cancer patients undergoing chemotherapy (US Patent). We have since studied the MOA using a newly developed in vitro potency assay (US Patent Pending) and are planning to conduct a pivotal Phase III clinical trial for CINV and file an NDA with the FDA. A sister dietary supplement product, Zindol® DS, has been reported to be safe and effective in motion sickness, and nausea and vomiting related to pregnancy, elective surgery and medications. We plan to conduct rigorous clinical trials for these indications after NDA approval of Zindol® for CINV in adult and pediatric populations.