Objectives: To define a study context that allows comparison of body contouring effects of potential body contouring drugs with deoxycholic acid (DA) at a dose regimen that demonstrates lipolytic effect in MRIs and is sufficiently tolerated to allow completion of the study. An additional objective is to demonstrate the advantages of 3-dimensional MRI imaging in conjunction with photo documentation of local post-injection reactions and blinded histopathological evaluation in providing a substantial basis for providing the rationale for further development of DBI-500 as an injectable body contouring drug.
Introduction: Expansion of DA use for body sculpting beyond unwanted submental fat has been hampered by an exaggerated local inflammatory reaction in a subpopulation of clients that cannot be prospectively identified and therefore excluded from treatment.
There were 408,000 body-sculpting procedures performed in 2017. In that year, the most frequent procedures were cryolipolysis (208,00), radiofrequency (89,000), followed by deoxycholic acid (46,000).
A potential alternative injectable agent should demonstrate superior efficacy and/or tolerability compared with DA.
Materials / method: Three minipigs were dosed with 0.5% or 1.0% of DBI-500, 1.0% DA, a combination of 1% DBI-500 + 1.0% DA, or placebo (saline). Each dose was administered 6 or 4 weeks prior to study end. Each dose consisted of 6 injections of 1mL for a total volume of 6 ml and injected 1.3 cm vertically. Injections for each dose group were done into tattooed grids of of 1 by 1 cm and a total area of 3 by 3 cm. These injections were 1 cm and 2 cm apart (sagital versus transverse plane).
Blinded histological slide review was performed by TPL Path Labs, Freiburg, Germany. Clinical assessments were also done.
Results: Review of serial MRIs in conjunction with 3D depictions (RadiANT™ Dicom Reader) of the injection areas clearly demonstrated reduction of subcutaneous fat deposits of both compounds. However, Post-injection photos of the injected areas indicate superior tolerability of DBI-500.
An experienced external histopathologist performed a blinded assessment of signs of inflammation in the respective histological slides. The analysis demonstrated a statistically significant reduction in inflammation scores (P<0.016) at 4 weeks. No significant effects on body weight or clinical labs were observed.
Conclusion: A minipig model utilizing MRIs and adequate density and depth of injections into dorsal subcutaneous fat is an efficient means of comparing potential injectable body contouring agents with that of the currently FDA-approved drug (deoxycholic acid).
Using this methodology, we were able to demonstrate at least comparable efficacy with superior tolerability of DBI-500 compared with DA at 5-fold greater volume per injection than recommended in the prescribing information of DA.
These results warrant further development of DBI-500 for body sculpting and cellulite.
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请注明名称（个人，公司，学会等等）: Co-founder of company
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请注明日期: Approved
和审阅情况: EU patent 2019
这项工作的完成感谢以下机构的支持： Dale Biotech, LLC.
