Phase I randomized double-blind placebo-controlled single-dose safety studies of Bowman-Birk inhibitor concentrate

Abstract

In previously performed animal studies and Phase I–II human trials, Bowman-Birk inhibitor concentrate (BBIC) appeared to be a promising cancer chemopreventive agent. The present study describes the results of two phase I randomized double-blind placebo-controlled trials performed in male subjects to assess the safety and toxicity of the original and new formulations of BBIC administered in a single dose as a suspension in orange juice. The dose of BBIC varied from 800–2,000 chymotrypsin inhibitor (CI) units. The BBI concentration in the serum samples collected from the subjects was analyzed by a dot-blot analysis procedure using the 5G2 monoclonal antibody, which is specific for reduced BBI. A total of 41 subjects were enrolled, 20 in the initial BBIC study and 21 in the second BBIC study. In these human trials, no clinically relevant changes in hematological or biochemical parameters were observed. Overall, BBIC was found to be well-tolerated. For these BBIC single-dose phase I trials, there was no dose-limiting toxicity for BBIC, even at the highest dose evaluated, and there were no apparent differences between the clinical trial results for the two formulations of BBIC. The bioavailability of BBI in the second clinical trial, which used the new BBIC formulation, was approximately 40 to 43% of the BBI bioavailability reached in the first clinical trial, which used the original BBIC formulation. The observed bioavailability difference was attributed to the different BBIC formulations used in these two clinical trials. These trials demonstrated that BBIC is safe when administered in a single dose of up to 2,000 CI units. Therefore, the results from the two trials indicate that a multi-dose trial of BBIC may be safely performed with doses of up to 2,000 CI units per day.

Soybean-derived Bowman-Birk inhibitor (BBI) blocks HIV entry into macrophages

“…As a natural product from soybean, BBI may have safety advantage in use for HIV prevention and therapy. It was reported that BBI concentrate (BBIC), a soybean extract enriched in BBI (Kennedy et al, 1993), had little toxicity effect in the phase I randomized double-blind placebo-controlled trials (Lin et al, 2014). Our in vitro experiments showed that BBI at the concentration of 100 μg/ml had little cytotoxicity effect on macrophages (Fig.…”

Soybean Bioactive Peptides and Their Functional Properties

“…It has demonstrated anti-carcinogenicity in different species including humans and tissue types including colon, liver, esophagus, breast, prostrate, and was considered as an FDA Investigational Drug in 1992 [ 57 , 108 ]. In both Phases I and II human trials, the BBI promised to be a safe cancer chemopreventive agent that prevents and suppresses malignant transformation and carcinogenesis at doses from 800 to 2000 chymotrypsin inhibitor units [ 108 , 109 ]. The mechanism by which BBI exerts its anti-cancer activity involves apoptosis through reactive-oxygen-species-induced mitochondrial damage after proteasomal inhibition and anti-angiogenesis [ 110 , 111 , 112 , 113 ].…”

Bowman-Birk Inhibitors: Insights into Family of Multifunctional Proteins and Peptides with Potential Therapeutical Applications

“…Therefore, the potencies of both-pure BBI and a soybean-derived extract enriched in BBI (known as BBIC)-are sometimes expressed in chymotrypsin inhibitor units (CIU). One CIU is the amount of a substance required to inhibit 1 mg of bovine pancreatic chymotrypsin [172,173].…”