E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
1) Patients with type 2 diabetes (T2D) and no or severely reduced kidney function, depending on chronic dialysis treatment.
2) Patients with T2D and normal kidney function. |
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E.1.1.1 | Medical condition in easily understood language |
1) Patients with type 2 diabetes (T2D) and no or severely reduced kidney function, depending on chronic dialysis treatment.
2) Patients with T2D and normal kidney function. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012347 |
E.1.2 | Term | Dependence on renal dialysis |
E.1.2 | System Organ Class | 10041244 - Social circumstances |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061835 |
E.1.2 | Term | Diabetic nephropathy |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 investigate safety parameters in patients with T2D and no or severely reduced kidney function treated with the antidiabetig drug liraglutide. Plasma concentrations of liraglutide and side effects will be closely monitored during intervention. Results will be compared with a group of patients with T2D and normal kidney function. |
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E.2.2 | Secondary objectives of the trial |
To investigate efficacy parameters in patients with diabetes and no or severely reduced kidney function treated with the antidiabetig drug liraglutide. Regulation of blood glucose, weight and cardiovascular parameters will be monitored. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Group 1)
· Male or female; aged 18-85 years
· Chronic severely impaired kidney function treated with chronic maintenance
dialysis
· Type 2 Diabetes
Group 2)
· Male or female; aged 18-85 years
· Normal kidney fuction
· Type 2 Diabetes
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E.4 | Principal exclusion criteria |
Group 1 and 2
· Type 1 diabetes mellitus
· Chronic pancreatitis / previous acute pancreatitis
· Known or suspected hypersensitivity to trial product(s) or related products
· Treatment with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors or other drugs, which in the Investigator’s opinion could interfere with glucose or lipid metabolism 90 days prior to screening
· Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder which in the investigators’ opinion could interfere with the results of the trial
· Inflammatory bowel disease
· Cardiac disease defined as: decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months
· Body mass index ≤ 18.5 kg/m2 or ≥ 50.0 kg/m2
· Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
· Clinical signs of diabetic gastroparesis
· Impaired liver function (transaminases >two times upper reference levels)
· Receipt of any investigational product 90 days prior to this trial
· Known or suspected abuse of alcohol or narcotics
· Screening calcitonin ≥50 ng/l
· Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the trough concentrations of liraglutide over time. It will be compared between patients with normal kidney function and patients in dialysis to evaluate the level of accumulation of liraglutide in patients undergoing dialysis treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation of the primary endpoint is expected after LPLV, ie ultimo 2013 |
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E.5.2 | Secondary end point(s) |
PD parameters:
- Postprandial plasma glucose, assessed by mean and peak PG values and AUC during a standard 4-hour meal test before and after intervention (optionel to dialysis patients).
- HbA1c, FPG; Body weight, Beta-cell surrogate markers, lipids, and other cardiovascular risk markers (ProBNP, CRP, vWF).
Safety of liraglutide will be evaluated by registration of
- AE´s
- Hypoglycaemic events divided into minor (BG<3.1 mM, and no need for assistance) or major (requiring assistance from third person). Registered by measurements from the CONTOUR® USB apparatus and questioning during trial visits.
The comparison of safety parameters will be performed both between active vs. placebo group of renal impaired patients, as well as between the two active liraglutide groups.
- Plasma concentration of liraglutide pre-, per- and post dialysis treatment (PD and HD).
- Concentration of liraglutide in dialysis fluid (PD and HD).
Other secondary endpoints
- Glycaemic control (assessed from 24-hour glucose profile, daily blood glucose measurements and HbA1c before, during and after intervention).
- Pancreatic beta-cell function (assessed from results of meal test before and after intervention and/or proinsulin-insulin ratio).
- Liver- and kidney function and homeostasis (blood samples before and after intervention)
- Cardiovascular parameters: Blood pressure, ECG, lipid profile and proBNP before and after intervention
- Markers of inflammation and endothelial function: vWF, CRP
- Insulin dose among participants treated with insulin at start of intervention
- Dose of oral antidiabetics among participants treated with oral antidiabetics at start of intervention
- Weight
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation of the secondary endpoints is expected after LPLV, ie ultimo 2013 |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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 last subject (LVLS) |
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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 |