E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Tacrolimus is a potent immunosuppressant agent widely used for the prevention and treatment of rejection in heart transplant recipients. While tacrolimus is typically administered in two divided doses per day, a new oral formulation with modified-release characteristics has recently been developed and licensed for use. Specifically formulated to enable once daily dosing, it was suggested that the benefit of the prolonged-release preparation maybe improved compliance. |
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E.1.1.1 | Medical condition in easily understood language |
While tacrolimus is administered in two doses per day, a new oral formulation with modified-release characteristics has recently been developed and licensed for use possibly improving compliance. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
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 |
- To compare tacrolimus concentration variability C0 of modified-release and standard tacrolimus formulations in heart transplant recipients. |
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E.2.2 | Secondary objectives of the trial |
- To compare the effects of modified-release and standard tacrolimus formulations on glucose metabolism in heart transplant recipients. - To compare the effects of modified-release and standard tacrolimus formulations on renal function in heart transplant recipients. - To evaluate the correlations between tacrolimus concentration variability and genotype in heart transplant recipients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient inclusion criteria will consist of all of the following: 1. Presence of triple immunosuppressive regimen, consisting of standard tacrolimus formulation, mofetil mycophenolate and steroids 2. Absence of significant cellular of antibody-mediated rejection within 3 months before enrollment. Acute cellular rejection will defined in accordance with International Society for Heart and Lung Transplantation (ISHLT) grading system (7) and significant acute cellular rejection was defined as ISHLT grade 2R or higher. Antibody-mediated rejection (AMR) will be defined according to the ISHLT working formulation for pathologic diagnosis of AMR (8) with significant AMR defined as pAMR 2 or higher. 3. Absence of infection episodes within 3 months before enrollment. An infection episode (bacterial, viral, fungal or protozoal) will defined as any infection requiring at least 1 week of intravenous antibiotic therapy (9). 4. Absence of allograft dysfunction within 3 months before enrollment. Allograft dysfunction will be defined as left ventricular ejection fraction (LVEF) <40% on standard echocardiography. 5. Absence of CAV defined as ISHLT CAV grade 1 or higher (10).
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E.4 | Principal exclusion criteria |
Patient exclusion criteria will consist of any of the following: 1. Presence of significant cellular of antibody-mediated rejection within 3 months after enrollment (run-in phase). 2. Presence of infection episode within 3 months after enrollment (run-in phase). 3. Variability of C0 tacrolimus concentration >30% within 3 months after enrollment (run-in phase).
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E.5 End points |
E.5.1 | Primary end point(s) |
Extended release tactolimus in non-inferior to standard release tacrolimus in C0 concentration variability in heart transplant recipients. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 monts after IMP initiation |
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E.5.2 | Secondary end point(s) |
- Extended release tactolimus improves glucose metabolism in heart transplant recipients. - Extended release tactolimus improves kidney function in heart transplant recipients. - A correlation exists between specific genotypes of CYP3A5 and Co variability. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 monts after IMP initiation |
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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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
standard release tacrolimus |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |