Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers
Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers
This is a phase 3, randomized, controlled, blinded, multicenter study conducted in 3 parallel
 cohorts of diabetic patients with at least 1 infected foot ulcer. Patients will be randomized
 to receive 1 of 3 study treatments; systemic antibiotic therapy and standard ulcer care with
 either (A) daily application of a gentamicin-sponge, (B) daily application of a
 placebo-sponge or (C) no-sponge, in the ratio 2:1:1. Patients will be treated for
 approximately 28 days and return to the clinic weekly for safety and efficacy assessments.
 After completing treatment, patients will return to the clinic for scheduled follow-up visits
 approximately 10, 30, 60 and 90 days after treatment is stopped.
This is a phase 3, randomized, controlled, blinded, multicenter study conducted in 3 parallel
 cohorts of diabetic patients with at least 1 infected foot ulcer. Patients will be randomized
 using an electronic randomization system to receive 1 of 3 study treatments; systemic
 antibiotic therapy and standard ulcer care with either (A) daily application of a
 gentamicin-sponge, (B) daily application of a placebo-sponge or (C) no-sponge, in the ratio
 2:1:1. The investigator will be blinded to the patient's treatment group assignment and
 patients randomized to one of the 2 sponge groups will be blinded as to whether the sponge is
 active or placebo.

 If a patient has multiple infected ulcers, the assigned treatment will be administered to all
 infected ulcers. The investigator will determine the highest severity ulcer to be used for
 all efficacy evaluations and will also determine the size and number of sponges (up to 4)
 that a patient will use in order to completely cover all infected ulcers. The investigator
 will prescribe an empiric systemic antibiotic therapy based on protocol instructions.

 Patients will be treated for approximately 28 days and return to the clinic weekly for safety
 and efficacy assessments. The investigator will stop study treatment if a patient achieves
 clinical cure by or after the 3rd treatment visit (approximately study day 15). After
 completing treatment, patients will return to the clinic for scheduled follow-up visits or
 until ulcer closure. The final efficacy assessments used in the primary efficacy analyses
 will be obtained at the first follow-up visit approximately 10 days after treatment is
 stopped. The remaining follow-up visits will occur at approximately 30, 60 and 90 days after
 treatment is stopped when patients will be assessed for ulcer closure and any re-infection.
-  Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria.

 -  Has at least 1 skin ulcer located on or below the malleolus that presents with the
 following clinical manifestations of a moderate or severe infection based on the
 Infectious Disease Society of America guidelines for the "Diagnosis and Treatment of
 Diabetic Foot Infections" (CID 2012; 54:132-173) (IDSA guidelines):

 -  has ≥ 2 manifestations of inflammation (local swelling or induration, erythema, local
 tenderness or pain, local warmth, purulent discharge (thick, opaque to white or
 sanguineous secretion)

 -  has ≥ 1 of the following characteristics: erythema > 2cm, or involving structures
 deeper than skin and subcutaneous tissues (e.g. abscess, osteomyelitis, septic
 arthritis, fasciitis) For patients with multiple infected ulcers, the ulcer with the
 highest Diabetic Foot Infection Wound score (DFI score) must be on or below the
 malleolus and all infected ulcers must be completely coverable using no more than 4
 sponges (sponges cannot be cut).

 -  Has documented adequate arterial perfusion in the affected limb(s) (either palpable
 dorsalis pedis and posterior tibial pulses, or normal Doppler wave forms, a toe blood
 pressure ≥ 45 mm Hg or participation is approved by a vascular surgeon)

 -  Has received appropriate surgical intervention to remove all necrotic and infected
 bone if diagnosed with osteomyelitis.

 -  Has received appropriate surgical debridement to remove all gangrenous tissue.

 Exclusion Criteria:

 Has a known history of hypersensitivity to gentamicin (or other aminoglycosides).

 -  Has a known or suspected hypersensitivity to bovine collagen.

 -  Has an ulcer infection which, based upon the patient's known history of
 hypersensitivity and/or as otherwise in the opinion of the investigator, cannot be
 adequately treated with at least one of the empiric systemic antibiotic regimens
 allowed by this protocol.

 -  Has an ulcer associated with prosthetic material or an implanted device.

 -  Has received any systemic or topical antibiotic therapy for any reason within 7 days
 of randomization unless it was administered to specifically treat the infected
 ulcer(s) and only within 36 hours of randomization.

 -  Requires or is likely to require treatment with any concomitant topical product or
 wound therapy before the first follow-up study visit.

 -  Is severely immunocompromised, or likely to become severely immunocompromised during
 the study, in the opinion of the investigator.

 -  Has a history of myasthenia gravis or other neurological condition where gentamicin
 use is contraindicated as determined by the investigator.

 -  Has a history of epilepsy.

 -  Has a history of alcohol or substance abuse in the past 12 months.

 -  Has an uncontrolled illness that, in the opinion of the investigator, is likely to
 cause the patient to be withdrawn from the trial or would otherwise interfere with
 interpreting the results of the study