Botanical Drug for Chemotherapy Induced Nausea and Vomiting

PROJECT SUMMARY
Nausea and vomiting are among the most distressing side effects of chemotherapy. This unmet need is acute
in the adult and pediatric populations undergoing chemotherapy and is the reason why up to 50% of patients
refuse subsequent chemotherapy treatment. Despite the widespread use of the 5-HT3 and NK-1 receptor
antagonist antiemetics, chemotherapy induced nausea and vomiting (CINV) continues to be reported by up to
70% of adult patients receiving highly emetogenic chemotherapy agents. These synthetic antiemetics are
expensive and burdened with significant side effects. Additionally, an off-label anti-psychotic olanzapine is
finding frequent use as a rescue medication despite its serious adverse side effects. There is a high unmet need
for improved products to treat CINV without adverse side effects.
To meet this unmet medical need, we are developing a botanical drug based on ginger which has been used for
centuries, from Aisa to Egypt and North America to manage gastrointestinal stress. The overall goal of this
proposal is to develop a highly purified and standardized ginger product, Zindol, as a botanical drug product for
the treatment of CINV. In Phase I, we plan to develop and manufacture an improved, highly purified active
pharmaceutical ingredient (API) of Zingiber Officinale as well as a formulated drug product (FDP) in gelatin
capsules, characterize these products, conduct stability studies and establish release criteria. We will also
perform an innovative in vitro nausea assays to define and control manufacturing. In Phase II, we will scale
manufacturing, conduct IND-enabling in vivo toxicology and pharmacology GLP studies, meet with the FDA and
establish the regulatory pathway for conducting clinical trials. In Phase III, we plan to conduct clinical trials on
Zindol® for the treatment of nausea and emesis in adults undergoing chemotherapy, and license the botanical
drug with strategic corporate partners to address the $3.4B marketplace.

Grant Number: 1R43AT013554-01
NIH Institute/Center: NIH
Principal Investigator: TREVOR CASTOR