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 general objective of the study is to show the positive benefits /risks balance of using the recombinant insulin formulation (Insuman Implantable 400 UI/ml) compared to the semi-synthetic insulin (Insuplant 400 UI).
Primary:
• To compare Insuman Implantable 400 IU/ml versus Insuplant 400 IU/mL with respect to the pump refill accuracy during a 4 refill cycle period (Comparative phase = 160+/- 20 days)
• To assess efficacy measured by HbA1 change in Insuman Implantable 400 IU/ml group versus Insuplant 400 IU/mL group after a 4 refill cycle period (comparative phase = 160+/- 20 days)
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E.2.2 | Secondary objectives of the trial |
Secondary:
• To assess efficacy, safety, refill accuracy evolution and device interventions during the open-label treatment period with Insuplant (insuplant non-comparative phase)
• To assess efficacy, safety, refill accuracy evolution and device interventions during the open-label treatment period with Insuman (insuman non-comparative phase)
• To evaluate daily insulin doses
• To assess the Anti-Insulin Antibodies (AIA = ADA) levels during the comparative phase
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Substudies to be run in selected centers
1) Pharmacokinetic parameters - breakfast profiles (3 centers): (Ctrough [predose insulin concentration], Cmax, Tmax, AUC0-4h free insulin) will be assessed in a subpopulation of 24 patients (12 patients per arm) at visit 2 and at the end of the comparative phase (V5).
2) Evaluation of the quality of Insuman implantable and Insuplant (one study center-12 patients): In-use stability (i.e. assay of insulin and phenol, related substances, high molecular weight proteins, pH) of insulin remaining in the pump reservoir before each new refill procedure will be assessed for 12 patients (1 sample for each patient will be assessed at each refill (comparative phase). At each pump refill, the remaining insulin in the vials (not used) will also be kept for analysis.
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E.3 | Principal inclusion criteria |
Inclusion criteria for comparative phase
• Patients already treated with Insuplant 400 IU/ml via a Medtronic MiniMed Implantable System 2007
• HbA1c ≤ 9.0%
• Patient showing a percentage of error at refill equal or below 20%
• Patient undergoing a NaOH rinse procedure of at least 10 minutes period with or without flush
Or
• Patient being re-implanted with a new pump (first fill with insulin)
• Signed informed consent form prior to enrolment
Inclusion criteria for Insuplant non-comparative phase
• Patients already treated with Insuplant 400 IU/ml via a Medtronic MiniMed Implantable System 2007
• Signed informed consent form prior to enrolment
Inclusion criteria for Insuman non comparative phase
• Participation to the comparative phase
Or
• Already treated with Insuplant
Or
• Being implanted with Minimed Implantable Pump
• Signed informed consent form prior to enrolment
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E.4 | Principal exclusion criteria |
Exclusion criteria for comparative phase
• Pump life time > 6 years
• Pump battery voltage < 2.6 volts
• Pregnancy or childbearing potential without a medically approved form of birth control
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoints:
• Refill accuracy between the 2 insulin groups after 4 refill cycles
The refill accuracy is calculated as a difference expressed in percentage between the theoretical refill volume calculated by the PPC using programmed values and the actual refill volume used by weight measurements
• HbA1c change from baseline in the 2 insulin groups after 4 refill cycles
Safety endpoints:
• Number of episodes of severe hypoglycaemia and non severe hypoglycaemia (<70 mg/dl) per patient (determined by SMBG or venous samples)
• Number of DKA episodes (pH<7.25),
• All adverse events,
• Anti-insulin antibody (ADAs) levels assessment (at Baseline (visit 1) and at each subsequent refill visit up to visit 5. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over 4 refill cycles (approximately 6 months) |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | 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) | 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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
non-comparative study coupled with a parallel open label phase and followed by an extension phase |
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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
| 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |