A Phase 3 Randomized, Placebo-Controlled, Blinded Study to Investigate the Safety and Efficacy of a Topical Gentamicin-Collagen Sponge in Combination with Systemic Antibiotic Therapy in Diabetic Patients with an Infected Foot Ulcer

• Register: EUCTR
• Last refreshed on: 9 January 2017
• Main ID: EUCTR2015-000934-31-AT
• Date of registration: 28/05/2015
• Prospective Registration: Yes
• Primary sponsor: Innocoll Pharmaceuticals Limited
• Public title: A Phase 3 Randomized, Placebo-Controlled, Blinded Study to Investigate the Safety and Efficacy of a Topical Gentamicin-Collagen Sponge in Combination with Systemic Antibiotic Therapy in Diabetic Patients with an Infected Foot Ulcer
• Scientific title: A Phase 3 Randomized, Placebo-Controlled, Blinded Study to Investigate the Safety and Efficacy of a Topical Gentamicin-Collagen Sponge in Combination with Systemic Antibiotic Therapy in Diabetic Patients with an Infected Foot Ulcer
• Date of first enrolment: 09/07/2015
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000934-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: No test article Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Poland, Slovakia, Spain, United Kingdom

Contacts

• Name: Clinical Trials Information
• Affiliation: Innocoll Pharmaceuticals Limited

• Name: Clinical Trials Information
• Affiliation: Innocoll Pharmaceuticals Limited

Key inclusion & exclusion criteria

Inclusion criteria:
A patient will be eligible for study participation if he/she meets the following criteria before enrollment:
1. Is aged = 18 and = 85 years.
2. Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria.
3. 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).
4. 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)
5. Has received appropriate surgical intervention to remove all necrotic and infected bone if diagnosed with osteomyelitis. [Note: The investigator is referred to Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161 for recommendations for the diagnosis of diabetic foot osteomyelitis.]
6. Has received appropriate surgical debridement to remove all gangrenous tissue.
7. If female, is nonpregnant (negative pregnancy test results 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. Is willing and able to return to the study facility for all follow-up visits.
10. Is able to fluently speak and understand the local language and is able to provide meaningful written informed consent for the study.
Once baseline clinical laboratory results become available, a patient will continue to be eligible for study participation after enrollment if he or she meets the following criteria:
11. Has the following laboratory values
• white blood cells (WBC) = 4000 cells/mm3 and/or absolute neutrophil count (ANC) = 1500 cells/mm3
• hematocrit > 25%,
• hemoglobin > 8 g/L,
• platelet count > 75 000/mm3
• coagulation test results less than 1.5 times the upper limit of normal (unless on anticoagulant therapy).
Any subject whose baseline laboratory results fall outside of these parameters will be withdrawn from the study.


Are the trial subjects under
Exclusion criteria:
A patient will be excluded from the study if he/she meets any of the following criteria:
1. Has a known history of hypersensitivity to gentamicin (or other aminoglycosides).
2. Has a known or suspected hypersensitivity to bovine collagen.
3. 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.
4. Has an ulcer associated with prosthetic material or an implanted device.
5. 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.
6. Requires or is likely to require treatment with any concomitant topical product or wound therapy before the first follow-up study visit.
7. Is severely immunocompromised, or likely to become severely immunocompromised during the study, in the opinion of the investigator.
8. Has a history of myasthenia gravis or other neurological condition where gentamicin use is contraindicated as determined by the investigator.
9. Has a history of epilepsy.
10. Has a history of alcohol or substance abuse in the past 12 months.
11. 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Diabetic Patients with an Infected Foot Ulcer
MedDRA version: 18.0 Level: PT Classification code 10021784 Term: Infected skin ulcer System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Product Name: Cogenzia
Pharmaceutical Form: Medicated sponge
INN or Proposed INN: GENTAMICIN SULFATE
CAS Number: 1405-41-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Medicated sponge
Route of administration of the placebo: Topical use (Noncurrent)

Primary Outcome(s)

Secondary Objective: To determine the effect of the gentamicin-sponge in combination with systemic antibiotic therapy compared to placebo-sponge and no-sponge, both in combination with systemic antibiotic therapy on microbiological outcome and eradication of baseline ulcer pathogens.

To assess the safety and tolerability of the gentamicin-sponge in combination with systemic antibiotic therapy.

Primary end point(s): The primary efficacy variable is the percent of patients with a clinical outcome of “clinical cure” at Follow-up visit 1.

Main Objective: To determine the effect of the Topical Gentamicin-Collagen Sponge (gentamicin sponge) in combination with systemic antibiotic therapy compared to placebo-sponge and no-sponge, both in combination with systemic antibiotic therapy on diabetic patients’ clinical outcome in the treatment of infected foot ulcers.

Timepoint(s) of evaluation of this end point: Follow-up visit 1.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: As per E.5.2

Secondary end point(s): The key secondary efficacy variables in order of hierarchy are as follows:
• Percent of patients with both a clinical outcome of “clinical cure” and “baseline pathogen eradication” at F/U visit 1
• Percent of patients with re-infection
• Time (days) to a clinical outcome of “clinical cure”
• Percent of patients that have an amputation associated with the target ulcer
• Percent of patients with target ulcer closure at or before F/U visit 2
• Time (days) to closure of the target ulcer

Other secondary efficacy variables are as follows:
• Percent of patients with a clinical outcome of “clinical cure” at the End-of-treatment visit
• Percent of patients with a clinical outcome of “clinical cure” at or before treatment visits 2, 3, 4, and 5
• Percent of patients with “clinical response” at End-of-treatment visit and at F/U visit 1, respectively
• Percent of patients with “clinical response” at or before treatment visits 2, 3, 4, and 5
• Time (days) to “clinical response”
• Percent of patients with “baseline pathogen eradication” at the End-of-treatment visit and at F/U visit 1, respectively
• Percent of patients with “baseline pathogen improvement” at the End-of-treatment visit and at F/U visit 1, respectively
• Percent of total baseline pathogens (all species from all subjects) eradicated at the End-of-treatment visit and at F/U visit 1, respectively
• Percent of patients with a microbiological outcome of “microbiological success”
• Percent of patients with a microbiological outcome of “microbiological response”
• Percent of patients with both a clinical outcome of “clinical cure” at F/U visit 1 and a microbiological outcome of “microbiological success”
• Percent of patients with both “clinical response” at F/U visit 1 and “microbiological response”
• Percent of patients with both “clinical response” and “baseline pathogen response” at F/U visit 1
• Percent of patients with target ulcer closure at or before each study visit (except F/U visit 2, which is evaluated as a key secondary efficacy variable)
• Percent of patients that have any surgical intervention (other than sharp debridement) associated with the target ulcer

Secondary ID(s)

2015-000934-31-CZ

INN-TOP-005

Source(s) of Monetary Support

Innocoll Pharmaceuticals Limited