E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Digital Ulcera in Systemic Sclerodermia patients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053400 |
E.1.2 | Term | Endothelin increased |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To demonstrate the correlation of blood flow in the hands and the extent of DU disease in patients with SSc. - Evaluate the effect of bosentan on the blood flow in the hands from baseline to 12 weeks, measured by laser Doppler imaging, in SSc subjects with a history of DU disease in the past 2 years and clinically relevant reduction of blood flow at baseline. |
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E.2.2 | Secondary objectives of the trial |
- Evaluate the effect of bosentan on the blood flow in different regions of the hands from baseline to 4 weeks and 12 weeks. -Evaluate the effect of bosentan on the hand function, pain perception and quality of life from baseline to 12 weeks, 26 weeks and 52 weeks. -Evaluate the effect of bosentan on the modified Rodnan skin score from baseline to 12 weeks, 26 weeks and 52 weeks. -Evaluate the effect of bosentan on the development of new digital ulcers and pitting scars from baseline to 12 weeks, 26 weeks and 52 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects > 18 years diagnosed with SSc; 2. Reduction of blood flow measured by laser Doppler imaging, of at least 50%, distally to the proximal interphalangeal joint, compared to historical healthy controls; 3. Women of childbearing potential must have a negative pregnancy test and use a reliable form of contraception; 4. A history of 1 or more DUs within 2 years prior to inclusion; 5. No use of bosentan in the past; 6. Subjects willing and able to sign informed consent. |
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E.4 | Principal exclusion criteria |
1. Parenteral prostanoid treatment for DU < 3 months ago; 2. Chronic treatment with PDE-5 inhibitor or ERA; 3. History of bosentan use; 4. Irreversible significant limitation of the hand function, e.g. amputation of more than one finger; 5. Other types of system- or connective tissue diseases; 6. Significant peripheral (macro-) vascular disease due to e.g. diabetes, hyperlipidemia, uncontrolled systemic hypertension, coagulopathy; 7. Any serious medical co morbidity (eg, active malignancy) such that the subjects life expectancy is < 12 months; 8. Known AST and/or ALT elevations higher than 3 times Upper Limit Normal (ULN); 9. Moderate to severe liver function disorder; 10. Pregnancy or breastfeeding; 11. Treatment with Glibenclamide, Fluconazole, Cyclosporin A, Tacrolimus or other calcineurin inhibitors; 12. Hypersensitivity for bosentan or one of its components; 13. Subjects not able to follow the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Correlation between blood flow in the hands, as measured by laser Doppler imaging, and extent of DU disease assessed by the mean blood flow restriction in four distinct groups of patients: patients without current DU (pitting scars allowed), patients with new DU (< 3 mo), patients with persistent DU (>3mo) and patients with significant tip-necrosis.
- Change in blood flow in the hands after 12 weeks of bosentan treatment compared to the baseline, as measured by laser Doppler imaging. |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 10 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 is defined by the last visit of the last subject. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |