ViaDerma Inc (VDRM)

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ABSTRACT in brief

Author: Christopher Otiko DPM

BACKGROUND

Diabetes affects almost a half a billion people globally with 23 million affected in the US. With about 83 million affected with condition designated as pre-diabetes. Of those with diabetes, 50% will develop peripheral neuropathy and/or diabetic ulcers. Of the 23 million people affected with diabetes, 25% will develop diabetic ulcers many will require expensive therapy or invasive surgical amputations.

OBJECTIVE

The goal of this study was to evaluate the efficacy and safety of FDA registered OTC Viabecline tetracycline hydrochloride. A topically applied antibiotic ointment designed for the treatment of diabetic foot ulceration.

RESEARCH DESIGN AND METHODS

Clinical investigation (CI) documenting the treatment effectiveness was estimated by enrolling consecutive patients in a multi-center outpatient clinic setting.

RESULTS

Viabecline was more effective than standard care, including IV antibiotics. The effect was greatest in those with the most severe wounds, i.e., large wounds that affect deeper anatomical structures. These patients were last resort patients that had failed all previous care and were headed to an amputation. In some cases even an amputation wasn’t feasible because of the patient’s cardiac status.

CONCLUSIONS

Viabecline is more than 96% effective in healing diabetic foot ulcers within 4 weeks. This effect is more pronounced in more severe wound, and the effect is the same whether the wound is infected or not.





BACKGROUND

Diabetes affects almost a half a billion people globally with 23 million affected in the US [2]. With about 83 million affected with condition designated as “pre-diabetes.”[3] Of those with diabetes, 50% will develop peripheral neuropathy and/or diabetic ulcers. [4] Of the 23 million people affected with diabetes, 25% will develop diabetic ulcers many will require expensive therapy or invasive surgical amputations [5].These wounds are often multifactorial in origin, but tend to occur on the plantar surface of the foot and arise in the setting of peripheral neuropathy, vascular compromise or both. Diabetic foot ulcers are associated with increased morbidity and mortality, and they have a negative impact on both the quality of life and the productivity of diabetic patients [6]. Almost 80,000 people (US) will require lower extremity amputations (LEAs) every year. Of those who require amputations, and depending on which study you choose, one year mortality rates of 10 to 50 percent, and the 5-year mortality rate post-LEA is between 30 and 80 percent.[7-12] Costing about $245 billion in 2012 and cost $365 billion in 2016 [13-15]

OBJECTIVE

The goal of this study was to evaluate the efficacy and safety of FDA registered Viabecline, tetracycline hydrochloride, a new topical antibiotic ointment. [16] Viabecline is a topically applied antibiotic designed for the treatment of diabetic foot ulceration as well as for other basic wound care needs.

RESEARCH DESIGN AND METHODOLOGY

Given the degree of severity of the patient’s condition(s) they were treated consecutively utilizing the multicenter approach. The majority of the patients were treated at Dr. Christopher Otiko practice and at various hospitals and rehab centers in Southern California.

Briefly, subjects were chosen for this study if they were patients with confirmed diabetes who had an ulcer on their foot. Additionally, 90% of these patients were “last resort” patients. Those selected to participate were patients who had failed all previous care and were headed for an amputation or had a non-healing wound for more than 6 months. In some cases even an amputation was problematic because of the patient’s cardiac status.

The wounds were classified using The Wagner-Meggitt classification is based mainly on wound depth and consists of 6 wound grades.[17] These include: grade 0 (intact skin), grade 1

(superficial ulcer), grade 2 (deep ulcer to tendon, bone, or joint), grade 3 (deep ulcer with abscess or osteomyelitis), grade 4 (forefoot gangrene), and grade 5 (whole foot gangrene) APPLICATION

Viabecline Protocol: One or two drops externally applied topical solution directly to the ulcer and rubbed into skin for 30 seconds three times daily. Ulcer was covered with non-sterile gauze dressing.

Patient data

Sex Male: 12. Female: 16

Average Age (years) 69.5

Wound area (cm2) average 1.89

Wound duration (weeks) 16

Wound grade 2.01?(1.98–2.04)

Diabetes type T1/8 – T2/20

Insulin dependent 6

Non-insulin dependent 22

Infected 8



CLINICAL OUTCOMES Study end point

We used an end point of 20 weeks for assessing whether a patient healed. However, 27 out of 28 patients healed within 4 weeks.

One patient who had an exposed necrotic extensor tendon took the longest; 12 weeks. He also had end stage renal disease and peripheral vascular disease which attributed to the delayed healing. Because we wanted to ensure adequate follow up we extended the treatment time to at least 12 weeks, our actual end point was a healed wound within the subsequent 4 weeks. We did this to be consistent with other studies on the efficacy of diabetic foot ulceration therapy. Many of these studies treated patients who had already failed to heal with standard therapy with an investigational agent for 20 weeks



CLINICAL OUTCOMES Study end point (continued)

Of the 28 patients in this study, 100% were treated with Viabeclne and healed by the 12th week of care Patients treated were more likely to have larger wounds, older wounds, and wounds of higher grade. Overall, 27 out of 28 patients (96% of patients) healed within 4 weeks of the initiation of care. The patient had an exposed necrotic extensor tendon took the longest to heal (12 weeks). The patient also had end stage renal disease and peripheral vascular disease which attributed to the delayed healing. His treatment continued at home where his daughter who was a Certified Nurse’s assistant (CNA) applied Viabecline 3 times daily until his ulcer healed in a total time of 12 weeks.

CONCLUSION

This study is the first independent assessment of the efficacy of Viabecline in the treatment of diabetic foot ulcers. We found that Viabecline is very effective in the treatment of diabetic foot ulceration. It appears that Viabecline can be used in minor wounds, but possibly, is more likely to be used in more severe wounds and may be more effective than standard care for severe wounds.

Most patients treated with Viabecline did not begin this treatment until the 3rd month with the ulcer and the Viabecline was the last resort. One patient had a confirmed diagnosis of MRSA that had not responded to 6 weeks IV Vancomycin treatment. Previous studies that examined the efficacy of treatments for diabetic foot ulceration have often used the cutoff of twenty (20) weeks of care. Our study revealed that we achieved healing after only 4 weeks of treatment. We used 20 weeks of care as our study end point. Viabecline treatment typically ended after only 4 weeks on average. Patients in our study had a four (4) week treatment period and a total 20-week observation follow up period. This is consistent with our in house pre-CI that suggests that most infections are under control in about a week and near complete wound recovery in four (4) to six (6) weeks. Previous established therapeutic strategies [18] could take up to twenty weeks (20) then the percentage of healed diabetic neuropathic foot ulceration levels off after approximately five (5) months. This indicates very little increased healing after the 20 week mark. Whereas 96% of our patients all healed within 4 weeks using Viabecline one (1) to three (3) times daily depending on the condition of the patient.

We found that Viabecline healed 96% diabetic neuropathic foot ulcers after 4 weeks of care when compared with treatment using standard care alone. The relative benefits of Viabecline over standard care persist for wounds of all sizes (with or without and infections) and the relative risk of healing using Viabecline versus standard care increases with wounds that are larger and more severe. In the setting of this study, these were also the patients more likely to be treated with Viabecline. Therefore, Viabecline represents an effective treatment for diabetic foot ulceration. Viabecline also appears to be effective in severe wounds, and may therefore play an important role in preventing amputation





CONCLUSION: Forward looking statement

Based on the positive results of the previous CI’s this investigator recommends further study into the efficacy of Viabecline topical antibiotic ointment. Initiating a phase two clinical investigation, including recruiting a larger cohort and using the multi-center approach and adding the double blind and placebo controls to further document the efficacy of the product and protocols. Successful implication of these protocols will positively affect clinical outcomes and be beneficial when used in expanding these procedures globally. Together this may lead to wide spread use and may reduce the staggering numbers of amputation’s and corresponding deaths, and may reduce the nearly 1.4 trillion dollars spent (US) yearly treating diabetes.

Conflict of Interest statement: Author states there is no conflict of interest issues related to this study

Acknowledgements David R Pozek

REFERENCES:



1) Author: Christopher Otiko DPM

6650 Reseda Blvd, Suite 101A, Reseda, Los Angeles County, CA 91335

2) In 2013, according to International Diabetes Federation, an est 381 million people had diabetes https://en.wikipedia.org/wiki/Epidemiology_of_diabetes_mellitus



3) In 2012, 29.1 million Americans, or 9.3% of the population, had diabetes.

http://www.diabetes.org/diabetes-basics/statistics/#sthash.7S3t2HMw.dpuf



4) Diabetic neuropathy is the most common complication of diabetes mellitus (DM), affecting as many as 50% of patients with type 1 and type 2 DM http://emedicine.medscape.com/article/1170337-overview



5) The Cost of Diabetes ADA http://www.diabetes.org/advocacy/news-events/cost-of-diabetes.html



6) 25% of the people with diabetes will develop foot ulcers http://www.medscape.com/viewarticle/821908



7) Diabetes is the leading cause of non-traumatic lower extremity amputations in the United States http://www.apma.org/Learn/FootHealth.cfm?ItemNumber=981

8) Tentolouris N, Al-Sabbagh S, Walker MG, et al. Mortality in diabetic and nondiabetic patients after amputations performed from 1990 to 1995: a 5-year follow-up study. Diabetes Care.

2004;27(7):1598–1604.

http://www.ncbi.nlm.nih.gov/books/NBK65149/

REFERENCES:

9) Larsson J, Agardh CD, Apelqvist J, et al. Long-term prognosis after healed amputation in patients Clin Orthop Relat Res. 1998;350:149–158.

[PubMed] http://www.ncbi.nlm.nih.gov/books/NBK65149/



10) Reiber GE, LeMaster JW. Epidemiology and economic impact of foot ulcers and amputations in people with diabetes. In:Bowker JH, Pfeifer M, editors. Levin and O’Neal’s the diabetic foot.

Philadelphia: Mosby- Elsevier; 2008. pp. 3–22. http://www.ncbi.nlm.nih.gov/books/NBK65149/

11) Diabetic foot infections are a frequent clinical problem. About 50% of patients with diabetic foot infections

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4218993/ have foot amputations die within five years.

12) According to the American Diabetes Association, the annual cost of diabetes, which affects 22.3 million people in the U.S., was $245 billion in 2012: $176 billion in excess health care expenditures and $69 billion in reduced workforce http://care.diabetesjournals.org/content/37/3/651 (2012)



13) Diabetes and prediabetes cost America $322 billion per year - : http://www.diabetes.org/diabetes- basics/statistics/infographics/adv-staggering-cost-of-diabetes.html#sthash.vas8Kkg4.dpuf (2016) http://www.diabetes.org/diabetes-basics/statistics/infographics/adv-staggering-cost-of- diabetes.html

14) Costs of treating diabetic wounds NZD(Of every 3.5 wound episodes, one required a major amputation)* Joret MO1, Dean A2, Cao C3, Stewart J4, Bhamidipaty V5. http://www.ncbi.nlm.nih.gov/pubmed/27565588

15) COSTS of Treating Diabete’s in the US AMERICAN DIABETIES Association

The American Diabetes Association (Association) released new research on March 6, 2013 estimating the total costs of diagnosed diabetes have risen to $245 billion in 2012 from $174 billion in 2007

http://www.diabetes.org/advocacy/news-events/cost-ofdiabetes.html?gclid=Cj0KEQjwxqS- BRDRgPLp0q2t0IUB



16) VIABECLINE- tetracycline hydrochloride (Topical ointment) V-LABS LLC



17) The Choice of Diabetic Foot Ulcer Classification in Relation to the Final Outcome http://www.medscape.com/viewarticle/430891_4



18) Wieman TJ, Smiell JM, Su Y: Efficacy and safety of a topical gel formulation of recombinant human http://www.ncbi.nlm.nih.gov/pubmed/9589248