E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne muscular dystrophy |
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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 | 10013801 |
E.1.2 | Term | Duchenne muscular dystrophy |
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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 determine whether the introduction of ACE-inhibitor (perindopril) combined with beta-blocker therapy (bisoprolol), before the onset of echo-detectable left ventricular dysfunction, can delay the age of onset and/or slow the rate of progression of cardiomyopathy in males with DMD. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Boys with proven DMD (defined out of frame deletion OR frame-shifting point mutation OR absent/<3% dystrophin on muscle biopsy);
• Age 7-12 years
• Normal left ventricular function on trans-thoracic echocardiography [defined as left ventricular ejection fraction > 60% [as calculated from 16 segment wall motion score method (see appendix C of trial protocol ID NCTU:ISRCTN50395346)]
• Left ventricular fractional shortening > 28% [for calculation – see appendix C of trial protocol ID NCTU:ISRCTN50395346]
• no global or regional wall motion abnormalities – refer appendix C of trial protocol ID NCTU:ISRCTN50395346 for use of 16-segment wall motion scoring system.
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E.4 | Principal exclusion criteria |
• Current or recent inclusion in another trial will not exclude participation in the DMD Heart Protection study.
• Contraindication to ACE-inhibitor or beta-blocker therapy (see SmPCs for perindopril (Appendix A of trial protocol) and bisoprolol (Appendix B of trial protocol ID NCTU:ISRCTN50395346) for contra-indications to these drugs).
• An initial echocardiogram of insufficient quality (see appendix C of trial protocol ID NCTU:ISRCTN50395346) to allow reliable measurements of ejection fraction, fractional shortening or wall motion (one repeat echocardiogram is permitted at baseline) may not enter the Trial.
• Renal function should be measured by plasma urea, creatinine and potassium prior to study entry. Patients with abnormal renal function [creatinine > upper limit of local laboratory range; typically > 120 mmol/l] or consistently abnormally high serum potassium level [K > upper limit of local laboratory range; typically 5 mmol/l] will also be excluded from the trial.
Inability to swallow a placebo capsule of the size to be used in the trial
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in left ventricular ejection fraction – measured by the 16-regional wall motion scoring system - compared to baseline, after a minimum of two years of combination therapy or placebo. To assess robustness of ejection fraction result, similar comparisons will be made for parameters of left ventricular end-systolic diameter, left ventricular wall motion index & left ventricular ejection fraction (%) and mitral flow to left ventricular tissue Doppler ratios (E/E’ ratios). |
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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 | No |
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) | 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 | No |
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 | 5 |
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 | 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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |