E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
Evaluate the effect of dalteparin compared to placebo on the healing of chronic neuroischaemic foot ulcers in diabetic patients with peripheral arterial occlusive disease (PAOD) and peripheral neuropathy, as determined by the number of patients who have ≥50% reduction in ulcer surface area including intact skin healing after a maximum of 6 months of treatment. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objectives are to evaluate the number of diabetic subjects with chronic neuroischaemic foot ulcers who had intact skin healing. The number of subjects who have required an amputation within the 6 month treatment period will also be investigated. The safety and tolerability of dalteparin compared to placebo in treatment of diabetic patients with neuroischaemic foot ulcers will also be evaluated. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects ≥18 years of age. 2. Subjects with type 1 or type 2 diabetes. 3. Subjects with peripheral occlusive arterial disease (PAOD) who have the following: • Thorough clinical assessment by the treating clinical team to exclude all other available PAOD treatment options (ie, revascularization etc) • Toe/arm blood pressure index ≤0.8. 4. Subjects must have a neuropathy disability score (NDS) of ≥3. 5. Subjects with chronic foot ulcers (defined as an ulcer for >2 months) and an ulcer area between 25-2500 mm2. All ulcers must have an ulcer staging of 1C and 2C according to the University of Texas wound classification system. 6. Subjects must be on a minimum of 75 mg of aspirin (or equivalent dose of calcium carbasalate or other acetylsalicylic acid therapy) daily for at least 4 weeks prior to randomization and the aspirin/calcium carbasalate or other acetylsalicylic acid therapy must be continued for the entire duration of the study. 7. Subjects with ulcer infections at screening as assessed by the presence of clinical signs of infection must be treated with appropriate antibiotics (in accordance to any available bacterial culture and sensitivity pattern results) prior to randomization. 8. Subjects must be willing to comply with the protocol, scheduled visits, laboratory tests and medication regimen. 9. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. |
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E.4 | Principal exclusion criteria |
1. Subjects who have undergone vascular reconstruction or angioplasty less than 1 months prior to randomization. 2. Subjects with an ulcer grading of 0 or 3 and staging of A, B or D according to the University of Texas wound classification system. 3. Subjects with a known bleeding disorder or evidence of active bleeding. 4. Subjects who are on dialysis. 5. Subjects with hepatic dysfunction defined as a prothrombin complex level <50 %. 6. Subjects with proliferative diabetic retinopathy that in the investigators opinion will result in an increased risk of hemorrhage if treated with dalteparin. 7. Subjects who have undergone a major organ transplant and/or treatment with immunosuppressive agents. 8. Subjects who have participated in a study of an investigational drug or device within four weeks of study entry. 9. Subjects with malignant ulcers, all subjects with clinically suspicious ulcers will require a biopsy to exclude a malignancy prior to enrollment. 10. Female subjects who are pregnant, lactating, or planning a pregnancy during the course of the study, or who are of child bearing potential and not using an acceptable method of birth control. Female subjects should continue contraceptive methods during the study and for at least 30 days after receiving their last treatment. 11. Subjects treated with anticoagulants or anti-platelet therapy other than aspirin such as warfarin or clopidogrel. 12. Abuse of alcohol and/or any other drug in the opinion of the investigator. 13. Subjects with contraindications to dalteparin administration, which include: • Known hypersensitivity to the active ingredient in dalteparin or to any of the excipients of this product. • History of confirmed or suspected immunologically mediated heparin induced thrombocytopenia. • Severe hypertension. • Acute gastroduodenal ulcer, cerebral hemorrhage or known hemorrhagic diathesis. • Subacute endocarditis. • Injuries to and operations on the central nervous system, eyes and ears (within the last month). 14. Subjects with any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the following:
• Number of subjects with ≥50% reduction in ulcer surface area including intact skin healing.
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
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 | Yes |
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |