E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic foot ulcer with mean diameter between 1.5 and 4 cm after débridement if indicated),
Wound stage Wagner grade I or II, Armstrong stadium A or C (for Wagner-Armstrong-Classification), treated unsuccessfully for at least 4weeks.
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E.1.1.1 | Medical condition in easily understood language |
Diabetic foot ulcers treated for at least 4 weeks unsuccessfully |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
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 assess which of three DPOCl doses is most effective compared to reference treatment in reducing wound sizes in the tested sample patient populations |
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E.2.2 | Secondary objectives of the trial |
• Wound area reduction (change between last visit and baseline), as measured by computerised wound area determination.
• Percentage of patients achieving complete wound closure.
• Time to complete wound closure
• Sustainability of wound closure within the 12 week treatment time frame.
• Course of wound closure over time.
• Improvement of subjective symptoms (itching, pain, well-being using Visual Analogue Scores (VAS))
• Improvement of objective clinical symptoms (prickling, heat sensation, cold sensation, numbness, furry
feeling, smell, exudation)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.The patient must have given written informed consent.
2.Age: ≥ 18 years, inclusive of the date of randomization.
3.Diabetic foot ulcer with mean diameter between 1.5 and 4 cm after débridement (1.5 and 4 cm if debridement is not indicated), determined as longest length + longest width)/2.
Wound shapes other than circular must have both a length and width of at least 1.5 cm;
Wound stage Wagner grade I or II, Armstrong stadium A or C treated unsuccessfully for at least 4weeks.
Should more than one eligible wound be present, only one will be selected (“target wound”)
Note: Other wounds with impaired healing, e.g. decubitus ulcer, arterial and/or venous leg ulcer, Charcot's foot or malum perforans, may be present in the same patient but shall not be selected as targets for the present study.
4.Type 1 or type 2 Diabetes Mellitus under metabolic control as confirmed by a glycosylated hemoglobin (HbA1c) ≤ 12% at screening
The laboratory results may not be older than 3 month at the date of randomization.
5.Adequate perfusion of the lower leg on the affected extremity determined by an ankle/ brachial ratio of >0.7 or systolic blood pressure of either > 50 mm Hg (big toe) or > 70 mm Hg (dorsalis pedis) as determined by an appropriate method, according to local use, concerning the foot pulse to exclude patients who require a revascularization therapy; examination results should be not older than 3 months
6.Females of non-childbearing potential defined as being amenorrhoeic for longer than 2 years with an appropriate clinical profile or surgically sterile.
If of childbearing potential the patient must use an adequate birth control and must have a negative pregnancy test.
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E.4 | Principal exclusion criteria |
1.Local antibiotic therapy of the target wound selected for the study.
2.Suspicion of bone infection or osteomyelitis* affecting the area of target wound.
3.Peripheral arterial occlusive disease in the pelvic region or lower. Note: The ulcer is primarily ischemic in etiology as diagnosed by an ABI of ≤ 0.7 on the affected extremity extremities or systolic pressure of ≤ 50 mmHg (great toe) or ≤ 70 mmHg (dorsalis pedis).
4.Vascular reconstruction or angioplasty less than 3 months ago or planned revascularization procedure.
5.Start or change of a new off-loading strategy (already existing off-loading device at the investigator´s discretion, is optimally applied and must be maintained)
6.Clinically significant abnormal values in clinical chemistry except those typical for the underlying diseases mentioned in the inclusion (for ranges see laboratory manuals of the laboratories of the participating sites/ countries). These exceptions are at the discretion of the Investigator and taken into account the tolerated ranges given in Section 11.3.8.
Note: Patients with a high blood glucose level are eligible, provided HbAc1 ≤12% at screening
7.Severe or uncontrolled heart disease (NYHA class III or IV, see Appendix 2).
8.Renal failure or treatment with dialysis.
9.Active severe hepatic disease, which might have an impact on wound healing.
10.Concurrent illness or a condition that may interfere with wound healing other than those mentioned in the inclusion criteria (e. g. carcinoma, hematological disease, vasculitis, connective tissue disease, alcohol neuropathy).
11.Previous radiation of the region of the target wound selected for the study.
12.Exposure to any systemic immunosuppressive or cytostatic therapy during the previous 30 days prior to the study, including the day Informed Consent is given.
13.Severe psychiatric or neurological disorder.
14.Incapability of giving informed consent .
15.Co-worker, student, relative or spouse of the investigator.
16.Previous participation in this present study.
17.Participation in another experimental clinical study during the previous 3 months prior to entry into the present study.
18.Current drug or alcohol abuse.
19.Any other significant disease or disorder which, in the opinion of the Investigator, may either put the patients at risk because of participation in the trial, or may influence the result of the trial, or the patient’s ability to participate in the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
Wound area reduction (percentage change between last visit and baseline as compared to baseline), as measured by computerised wound area determination |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Wound area reduction (change between last visit and baseline), as measured by computerised wound area determination.
• Percentage of patients achieving complete wound closure.
• Time to complete wound closure
• Sustainability of wound closure within the 12 week treatment time frame.
• Course of wound closure over time.
• Improvement of subjective symptoms (itching, pain, well-being using Visual Analogue Scores (VAS))
• Improvement of objective clinical symptoms (prickling, heat sensation, cold sensation, numbness, furry feeling, smell, exudation)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
3 blinded doses of IMP versus comparator |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Hartmann Hydrosorb® dressing |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | No |
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 |
Estonia |
Georgia |
Latvia |
Ukraine |
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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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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
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 | 5 |