E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic patients with a mild infection of a lower extremity skin ulcer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012664 |
E.1.2 | Term | Diabetic foot ulcer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the safety and efficacy of the topical gentamicin-collagen sponge (gentamicin sponge) combined with standard of care (daily wound care, off-loading, diabetic control and debridement by a physician or podiatrist), compared to oral levofloxacin combined with standard of care, in the treatment of mildly infected skin ulcers. |
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E.2.2 | Secondary objectives of the trial |
- To determine the effect of the gentamicin sponge compared to oral levofloxacin on eradication of wound pathogens
- To assess the effect of the gentamicin sponge compared to levofloxacin on absolute and percent decrease of total wound surface area. Total wound surface area will be calculated by a third party, blinded to all patient data and regimen, using wound tracings
- To assess the systemic exposure to gentamicin following the administration of the gentamicin sponge by measuring serum gentamicin concentrations at various time points after applying the sponge. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Is a man or woman aged 18 to 75 years. 2. Has diabetes mellitus, according to the American Diabetes Association criteria. 3. Has a single infected skin ulcer below the knee, defined as “mild” by the Infectious Disease Society of America (IDSA) Guidelines, for whom, in the Investigator’s judgment, topical or oral antimicrobial therapy is appropriate (IDSA Guidelines, CID 204;39:885-910).
Mild infection severity: The presence of ≥ 2 manifestations of inflammation (purulence or erythema, pain, tenderness, warmth or induration) but any cellulitis/erythema extends ≤ 2 cm around the ulcer, and the infection is limited to the skin or superficial subcutaneous tissue, with no other local complications or acute, systemic illness.
4. Has had an x-ray of the infected area within the 2 days immediately preceding or at Visit 1 (Baseline/Randomization) that is negative for osteomyelitis. 5. Meets the following laboratory criteria: • Hemoglobin (Hb) > 10 g/dL. • White blood cells (WBC) ≥ 4000 cells/mm3 and/or absolute neutrophil count (ANC) ≥ 1500 cells/mm3. • Calculated creatinine clearance (CLcr) of ≥ 20 mL/min (using the Cockroft-Gault equation). • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) within 3x the upper limit of normal. • Hemoglobin A1C (HbA1C) < 10%. 6. Has an ankle-brachial index (ABI) ≥ 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 ≥ 40 mm Hg on the limb with the target ulcer.) 7. If female, is nonpregnant (negative pregnancy tests at the Baseline/ Randomization Visit) and nonlactating. 8. 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 1 of the following medically-acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study: • Oral, implantable or injectable contraceptives for 3 consecutive months before the Baseline/Randomization Visit. • Total abstinence from sexual intercourse (≥ 1 complete menstrual cycle before the Baseline/Randomization Visit). • Intrauterine device (IUD). • Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream). 9. Willing to return to the study facility for the Final Study Visit. 10. Must be able to fluently speak and understand English and be able to provide meaningful written informed consent for the study. |
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E.4 | Principal exclusion criteria |
1. 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. 2. Has a known hypersensitivity to bovine collagen. 3. Has any uncontrolled illnesses that, in the opinion of the Investigator, would interfere with interpreting the results of the study. 4. Has an infecting pathogen known to be intermediate or resistant in vitro to levofloxacin. Patients enrolled into the study presumptively will be discontinued if their cultured organism is intermediate or resistant to levofloxacin. 5. Has a target ulcer with a wound size > 5 × 5 cm. 6. Has gangrenous tissue of the affected limb that cannot be removed with a single debridement. 7. Has a wound associated with prosthetic material or device. 8. Received any topical or systemic antimicrobial therapy within the 2 weeks prior to study entry (Visit 1 [Day 1]). 9. Has documented osteomyelitis. 10. If severely immunocompromised, may be excluded at the discretion of the Investigator. 11. Has a history of alcohol or substance abuse in the past 12 months. 12. Is undergoing dialysis (renal or peritoneal) or has history of kidney transplant. 13. Has a history of myasthenia gravis or other neurological condition where gentamicin use is contraindicated as determined by the Investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the percent of patients with a clinical outcome of “clinical cure” in each treatment group at the Final Study Visit.
Clinical cure is defined as: The resolution of all signs and symptoms of infection (purulence or evidence of inflammation) that were present at enrollment and the patient requires no further antimicrobial therapy or surgical intervention to treat the infection. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will be the last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |