SBIR-STTR Award

In phase 1 the investigators demonstrated that the purified isoflavonoid glycoside puerarin (NPI-031G), isolated from kudzu (pueraria lobata), is effective in reducing alcohol intake in rats. The objective of phase 2 is to 1) refine the isolation procedures using a novel high-speed countercurrent chromatographic method, 2) evaluate its effect on alcohol drinking, withdrawal symptoms, and anxiety after acute and chronic administration in rats, 3) generate preclinical data on pharmacokinetic, tissue distribution, and chronic toxicity, and 4) study the mechanism of action. Results will be applied for an Investigational New Drug (IND) application to conduct future clinical studies and subsequent commercial development.

Thesaurus Terms:
alcoholism /alcohol abuse chemotherapy, angiosperm, glycoside, plant extract alcoholic beverage consumption, pharmacokinetics laboratory rat

This application is a resubmission in response to AA-04-002 from the National Institute on Alcohol Abuse and Alcoholism to continue our STTR (Phase I and II) study on the development of NPI-031G (Puerarin), an Isoflavone-C-glycoside isolated from Puerira lobota (Kudzu), as a botanical anti-craving agent for the treatment of alcohol drinking problems. In STTR Phase II, we showed that chronic oral administration of NPI-031G (150 mg/kg/day) suppressed daily alcohol drinking by almost 50 percent in animals throughout a 4-week study (see Preliminary Data Section C). Recently, we demonstrated that the extract of kudzu, which contains 20 percent NPI-031G, reduces alcohol intake significantly in heavy alcohol drinkers. In this continuing application, we propose to complete the preclinical work, including a toxicity study in year 01 and 02, a prerequisite for an IND application. In year 03, we will focus on clinical evaluation in human alcoholics. Specifically, we will conduct the following studies. Year 01: 1) Synthesis of radio-labeled NPI-031G; 2) Purification of NPI-031G (>99.0 percent) for clinical study; 3) Bioavailability and pharmacokinetic study; and 4) Toxicity studies (mutagenic, acute toxicity). Year 02: 1) Chronic toxicity study; 2) In vitro and in vivo drug metabolism studies; 3) Preparation of Drug Master File (DMF); 4) Request for IRB approval, 5) Submission of IND application; and 6) Phase I safety and alcohol challenge study in humans. Year 03: 1) Preparation of NPI-031G and placebo capsules under GMP conditions; 2) Effects on brain alcohol levels (humans); 3) Effects on cerebral blood flow in human; and 4) Human alcohol self-administration in natural setting. The proposed pre-clinical and clinical studies are necessary steps toward the commercial development of NPI-031G. NPI, Inc. has also prepared a comprehensive business plan for further development of NPI-031G as an anti-craving agent in collaboration with a pharmaceutical company in the US (Business Plan in Appendix).

Thesaurus Terms:
Alcoholic Beverage Consumption, Alcoholism /Alcohol Abuse, Alcoholism /Alcohol Abuse Chemotherapy, Drug Design /Synthesis /Production, Flavone, Glycoside, Plant Extract Brain Circulation, Chemical Synthesis, Drug Metabolism, Drug Screening /Evaluation, Pharmacokinetics, Psychopharmacology Clinical Research, Human Subject, Laboratory Rat, Magnetic Resonance Imaging, Radiotracer