E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
The primary objective of this study is to assess whether treatment with an enteric coated formulation of mycophenolic acid (MPA) permits higher MPA doses to be maintained, than treatment with standard MMF therapy, in patients with demonstrated susceptibility to gastro intestinal side effects |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to determine the effect of the use of the enteric coated formulation of MPA on patient reported outcomes, in patients who warrant conversion from MMF or require a reduced dose of MMF because of GI side effects. Symptom severity is assessed by the Gastrointestinal Symptom Rating Scale (GSRS) and Bristol stool form chart; HRQL is assessed by the Gastrointestinal Quality of Life Index (GIQLI) and SF-36. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Patients that have received a kidney transplant; 2. Receiving immunosuppressive regimen that includes MMF; 3. Patients suffering GI side effects related to standard MMF doses or patients on reduced dose MMF with existing but tolerated/controlled GI side effects. 4. At least 18 years of age; 5. Willing to provide written informed consent; 6. Able to meet all study requirements and completing three study visits.
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E.4 | Principal exclusion criteria |
1. Patients with GI symptoms assumed or known not to be caused by MPA therapy (e.g. oral bisphosphonate induced, infectious diarrhea); 2. Acute rejection < 1 week prior to study enrollment; 3. Women of child-bearing potential who are planning to become pregnant or are pregnant and/or lactating who is unwilling to use effective means of contraception; 4. Presence of psychiatric illness (i.e., schizophrenia, major depression) that, in the opinion of the site investigator, would interfere with study requirements; 5. Undergoing acute medical intervention or hospitalization; 6. Any other medical condition that, in the opinion of the site investigator based on recall or chart review would interfere with completing the study, including but not limited to, visual problems or cognitive impairment. 7. Receiving any investigational drug or have received any investigational drug within 30 days prior to study enrollment.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy assessment will be based on the proportion of patients who are maintained at Visit 4 on a dose that is at least one dosage step greater than at baseline (Visit 2). Table 6.1 shows the dosage steps corresponding to 25%, 50% and 100% of the target therapeutic dose for each drug.
The main secondary efficacy assessment of GI complaints will be based on changes from baseline to Visits 3 and 4 in the diarrhoea and indigestion subscales of the GSRS instrument and compared between the Myfortic and standard therapy groups. For GSRS, a higher score represents greater impairment of quality of life due to GI symptoms. The comparisons between the groups will be based on confidence interval as well as hypothesis testing approaches. An analysis of covariance (ANCOVA) model will be fitted including terms for treatment, dose level (expressed as a proportion of the target therapeutic dose), baseline GSRS, and centre. The possibility of a treatment by centre interaction, or a treatment by baseline GSRS interaction will be examined, although the interaction terms will not be included in the primary analysis model. The least squares mean (“adjusted mean”) change from baseline for each treatment group, the difference in the least squares mean changes between the two treatment groups (Myfortic - MMF), and the two-sided 95% confidence interval for the difference will be obtained from the primary analysis model and presented. As a guide to aid interpretation, the minimum clinically important difference on the GSRS is 0.50. Bristol stool chart: Summary statistics will be provided for the frequencies in each category of the chart and changes from baseline presented.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
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) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Current therapy - Cellcept |
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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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 last patient. |
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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 | 3 |
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 | 3 |