E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bone Health in Duchenne Muscular Dystrophy- a randomised controlled study of Risedronate use |
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MedDRA Classification |
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 |
(1)To prospectively determine, using a randomized controlled trial, the effects of a targeted intervention on improving BMD in this population using oral bisphosphonate and calcium and Vitamin D supplementation (Calcichew D3 Forte) versus Calcium and Vitamin D supplementation with Calcichew D3 Forte alone.
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E.2.2 | Secondary objectives of the trial |
(2)To assess bone health in Irish population of children and young adults with DMD a) Baseline calcium and vitamin D status and optimize prior to onset of trial b) Baseline bone mineral density in ambulant and nonambulant boys with DMD, using DXA scan and markers of bone formation and resorption. DXA performed up to six months prior to the onset of the trail will be used as a baseline measurement. c) Determine the incidence of long bone and vertebral fractures and bone pain in this group and whether there is any correlation with disease severity/steroid use or genetic mutations. (3) To establish guidelines on management of bone health in the DMD population to reduce fracture risk.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.>/4 years old at time of initiation of study 2. Z score as measured by DXA >1.0 S.D. below the mean 3. boys only with DMD |
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E.4 | Principal exclusion criteria |
1. Hypersensitivity to Risedronate sodium 2. <4years at time of initiation of study 3. Previous bisphosphonate use 4. Uncorrected hypocalcaemia, uncorrected low Vitamin D 5. Inability to stay in an upright position (sitting or standing) for at least 30minutes 6. Severe renal impairment (creatinine clearance <30ml/min) 7.Undergoing invasive dental treatment 8. History of recent or active oesophageal or upper gastrointestinal problems 9.History of oesophageal disorders which delay oesophageal transit or emptying e.g. stricture or achalasia 10. Involvement in clinical trial in the preceding 12 weeks. 11. Learning difficulties in carer resulting in difficulties comprehending treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome: Efficacy of bisphosphonates and Calcium and Vitamin D supplementation with Calcichew D3 Forte, compared with Calcium and Vitamin D supplementation (Calchichew D3 Forte) alone
a. Change /% change in areal/volumetric BMD Z score of lumbar spine following intervention over 12 months is the primary endpoint. Criteria for success of treatment will be an increase of 0.5SD in lumbar spine Z score as measured by DXA scan. The doctor reporting the DXA scans (MMcK) will be blinded to what treatment each patient is receiving. Our study is large enough to detect a difference of 0.8SD in lumbar spine DXA score between treatment and control groups.
b. Change /% change in areal/volumetric BMD Z score of lateral distal femoral head, distal third of radius, total body excluding head as measured by DXA
Our power calculation is based on the primary end point of lumbar spine BMD Z-score changes. Because stratified randomization has only a minor effect on power for a superiority trials such as this standard two-group comparison power calculations were used Based on a two-sided significance level of 5% and a power of 80%, a trial with 25 patients in each group would be able to detect a difference in BMD lumbar spine Z-score changes of 0.81 standard deviations (SD) or greater after 12months treatment. This change in BMD lumbar spine Z score has been reported by previous groups using similar dose regime.
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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) | 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 | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | 2 |
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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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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
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 |