A Trial to Assess Safety and Efficacy of Topical MBN-101 in Patients With Moderate/ Severe DFI
A Trial to Assess Safety and Efficacy of Topical MBN-101 in Patients With Moderate/ Severe DFI
This is a randomized, double-blind, placebo-controlled, multi-center study, in patients with
 moderate to severe diabetic foot infection (DFI), that will be conducted in two parts. In
 Part I, patients will be enrolled into 1 of 3 escalating dose cohorts at a ratio of 3:1
 (Active to Placebo). In Part II, patients will be randomized in a 1:1 ratio (Active to
 Placebo) based on the optimal dose demonstrated in Part I. Patients will be randomized to
 receive either topical application of MBN-101 or topical application of vehicle, applied
 directly to the target site, 3 times per week, for a minimum of 14 days and up to a maximum
 of 21 days. All patients will also receive systemic antibiotic treatment.
This is a randomized, double-blind, placebo-controlled, multi-center study that will be
 conducted in two parts. In Part I, patients will be enrolled into escalating dose cohorts
 (150, 375, or 600 µg/mL) (N=16/cohort) at a ratio of 3:1 (Active to Placebo). In Part II,
 patients will be randomized in a 1:1 ratio (Active to Placebo) based on the optimal dose
 demonstrated in Part I.

 Patients with diabetes mellitus and a foot infection with an Infectious Disease Society of
 America (IDSA) infection severity rating of moderate or severe will be eligible for the
 trial. Both inpatients and outpatients are eligible if they meet all inclusion/exclusion
 criteria, however all enrolled patients must remain in-hospital for the first 24 hours after
 initial dosing. Patients with a need for surgical therapy (e.g., incision and drainage or
 removal of necrotic tissue) beyond standard bedside wound debridement should not be enrolled.

 Patients will be randomized to receive either topical application of MBN-101 or topical
 application of vehicle, applied directly to the target site, 3 times per week, for a minimum
 of 14 days and up to a maximum of 21 days. The determination to stop topical antibiotic
 therapy will be at the discretion of the principal investigator, and should be based on the
 resolution of findings of infection. All patients will also receive systemic antibiotic
 treatment based on the protocol defined algorithm. Systemic antibiotic therapy should
 continue until, but not beyond, the resolution of findings of infection, as outlined in the
 2012 IDSA clinical practice guideline for the diagnosis and treatment of diabetic foot
 infections,
Inclusion Criteria:

 -  Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria

 -  Has a foot infection as defined by the IDSA guidelines, with a severity rating of
 moderate or severe

 -  Either no current or recent (within 72 hours) antibiotic therapy for the DFI,

 -  Has documented adequate arterial perfusion in the affected limb (either palpable
 dorsalis pedis or posterior tibial pulses, or normal Doppler wave forms, or a toe
 blood pressure ≥ 45 mm Hg, or an ankle-brachial index (ABI) of >0.6)

 Exclusion Criteria:

 -  Proven or highly suspected, involvement of bone (i.e., osteomyelitis)

 -  More than one concurrent, infected, diabetic foot ulcer

 -  Hemoglobin A1c > 11 on the day of presentation

 -  Requirement for ongoing immunosuppressive therapy (topical or inhaled corticosteroids
 are permitted)

 -  Serum creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or
 Alkaline Phosphatase >2 times the upper limit of the normal range of the local testing
 laboratory

 -  Absolute neutrophil count <1000

 -  Any condition that has required treatment with any other bismuth containing compound
 within the last 2 weeks (i.e., Kaopectate or Pepto-Bismol)

 -  Participation in an investigational trial to evaluate pharmaceuticals or biologics
 within the past 3 months

 -  Need for any surgical therapy beyond debridement to treat the diabetic foot ulcer
 (e.g., incision and drainage, removal of necrotic tissue)

 -  Planned lower extremity amputation that will include their infected ulcer

 -  Known allergy to bismuth and/or MBN-101 excipients (methylcellulose, Tween 80
 (polysorbate 80))

 -  Female patients who are pregnant, lactating, or who have a positive serum human
 chorionic gonadotropin (pregnancy) as determined by laboratory testing

 -  Immunocompromised due to illness or organ transplant

 -  History of any type of cancer (excluding non-melanoma localized skin cancer or
 completely excised and cured carcinoma-in-situ of uterine cervix)

 -  History of major medical noncompliance

 -  Other medical conditions which, in the opinion of the Principal Investigator, would
 jeopardize the safety of the study subject or impact the validity of the study results