Official Title: “A Randomized, Controlled, Open Label Study of the Safety and Efficacy of a Topical Gentamicin Collagen Sponge Combined With An Antibiotic Compared to Antibiotic Therapy Alone in Diabetic Patients With Moderately Infected Foot Ulcers”

The purpose of this study is to determine whether the gentamicin-collagen sponge (Collatamp G topical) when combined with standard daily wound care and an oral antibiotic (levofloxacin) is safe and effective in treating moderately infected skin ulcers compared to treatment only with standard daily wound care and an oral antibiotic (levofloxacin).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2009

Infected skin ulcers with diabetes can be very debilitating because they are difficult to heal. Diabetic ulcers are responsible for frequent health care visits, and are a major predictor of amputation. Diabetic ulcers can be caused by a patient's inability to sense pain or warmth as well as peripheral vascular disease, which causes diminished blood flow to the foot. Early aggressive treatment is necessary to treat infection and ultimately prevent the need for amputation.

Gentamicin is an antibiotic that is effective in treating certain kinds of infection.

Collagen is a protein that is found in all mammals. The gentamicin-collagen sponge is a thin flat sponge made out of collagen that comes from cow tendons and containing gentamicin. When applied to an open ulcer, the collagen breaks down and the gentamicin is released into the ulcer, but very little is absorbed into the blood stream. The high levels of gentamicin in the open infected ulcer may help treat the infection.

In this study, all subjects will be given the necessary supplies and taught how to take care their foot ulcer. All subjects will also receive oral an antibiotic (levofloxacin).

Additionally, subjects who are randomly assigned to receive the gentamicin-collagen sponge will place a gentamicin-collagen sponge on their ulcer during daily wound care.

Intervention(s) in this Clinical Trial

• Drug: gentamicin-collagen sponge and levofloxacin
  • Collatamp G Topical Gentamicin Collagen Sponge: 10 × 10 cm in size containing 280 mg of Type I bovine collagen and 200 mg of gentamicin sulfate (equivalent to 130 mg gentamicin base) OR 5 × 5 cm in size containing 70 mg of Type I bovine collagen and 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) (gentamicin sulfate 2 mg/cm2 [equivalent to 1.3 mg/cm2 of gentamicin base]), depending on the size of the wound. The patient will continue using the same size sponge for the duration of the study. And 750 mg tablet po every 24 hours or 750 mg IV administered by slow infusion over 90 minutes every 24 hours.
• Drug: Levofloxacin only
  • levofloxacin, 750 mg tablet po every 24 hours or 750 mg IV administered by slow infusion over 90 minutes every 24 hours

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Gentamicin sponge applied into wound plus levofloxacin, 750 mg by mouth (po) or intravenous (IV) every 24 hours or, if ulcer culture results show resistance to levofloxacin, alternative antimicrobial therapy as determined by susceptibility testing
• Active Comparator: B
  • Levofloxacin, 750 mg po or IV every 24 hours or, if ulcer culture results show resistance to levofloxacin, alternative antimicrobial therapy as determined by susceptibility testing

Primary Measures

• The percent of patients with a clinical outcome of "clinical cure" in each treatment group at Visit 3
  • Time Frame: Day 7 of treatment
    Safety Issue?: No

Secondary Measures

• The percent of patients with a positive clinical response at each time point
  • Time Frame: Every time point
    Safety Issue?: No
• The percent of patients with a "clinical cure"
  • Time Frame: Every time point
    Safety Issue?: No
• The percent of patients with pathogen eradication
  • Time Frame: Every timepoint
    Safety Issue?: No
• Absolute change in total wound surface area in each treatment group
  • Time Frame: Every time point
    Safety Issue?: No
• Time to clinical cure
  • Time Frame: Actual time assessed
    Safety Issue?: No
• Time to positive clinical response
  • Time Frame: Actual time assessed
    Safety Issue?: No
• Time on parenteral antimicrobial therapy
  • Time Frame: Actual time assessed
    Safety Issue?: No
• Visual Analog Scale (VAS) for pain assessment
  • Time Frame: Every timepoint
    Safety Issue?: No
• Lipsky wound score
  • Time Frame: Every timepoint
    Safety Issue?: No
• Treatment emergent adverse events
  • Time Frame: Throughout study period
    Safety Issue?: Yes

Inclusion Criteria:

• Is a man or woman aged ≥ 18 and ≤ 80 years.
• Has diabetes mellitus, according to the American Diabetes Association criteria.
• Has a single infected skin ulcer below the knee, defined as "moderate" by the Infectious Disease Society of America (IDSA) Guidelines for whom, in the Investigator's opinion, intravenous (IV) or oral antimicrobial therapy is appropriate
• Has had an x ray of the infected area within the 2 days immediately preceding or at Visit 1 (Baseline/Randomization) to document the presence or absence of osteomyelitis.
• Patients with osteomyelitis must receive appropriate surgical intervention to remove all necrotic and infected bone and otherwise meet enrollment criteria before being enrolled in the study.
• Meets certain minimal laboratory criteria
• Has an ankle brachial index (ABI) > or = 0.7 and ≤ 1.3. (Note: Patients with ABI
• < 0.7 or > 1.3 may be included if they have either a transcutaneous oxygen pressure or a toe pressure > or = 40 mm Hg on limb with ulcer.)
• If female, is nonpregnant (negative pregnancy test results at the Baseline/Randomization Visit) and nonlactating.
• If female, is either not of childbearing potential (defined as postmenopausal for ≥ 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing a medically acceptable methods of birth control and agrees to continue with the regimen throughout the study
• Willing to return to the study facility for the Final Study Visit.
• Must be able to fluently speak and understand English and be able to provide meaningful written informed consent for the study.

Exclusion Criteria:

• Has a known history of hypersensitivity to gentamicin (or other systemic aminoglycosides) or levofloxacin or drugs in the same class, or any of the test article or reference product components.
• Has a known hypersensitivity to bovine collagen.
• Has any uncontrolled illnesses that, in the opinion of the Investigator, would interfere with interpreting the results of the study.
• Has a target ulcer with a wound size > 10 × 10 cm.
• Has gangrenous tissue of the affected limb that cannot be removed with a single debridement.
• Has wound known to contain isolates resistant to levofloxacin.
• Has a wound associated with prosthetic material or device.
• Received any topical or systemic antimicrobial therapy within the 2 weeks prior to study entry (Visit 1 [Day 1]).
• If severely immunocompromised, may be excluded at the discretion of the Investigator.
• Has a history of alcohol or substance abuse in the past 12 months.
• Has serum creatinine > 3 mg/dL, is undergoing dialysis (renal or peritoneal) or has a history of kidney transplant.
• 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 tendon disorders related to fluoroquinolone administration

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Innocoll Technologies

Overall Clinical Trial Officials and Contacts

David Prior Study Director Innocoll Technologies  

Overall Contact: Lisa Hemsen 860-610-5530 skinulcers@premier-research.com

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00659646

Study ID Number: INN-TOP-003

ClinicalTrials.gov Identifier: NCT00659646

Health Authority: United States: Food and Drug Administration