E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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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 confirm the superiority of liraglutide versus placebo as add-on to existing oral antidiabetic drug (OAD) and/or insulin therapy on glycaemic control after 26 weeks treatment in subjects with type 2 diabetes and moderate renal impairment |
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E.2.2 | Secondary objectives of the trial |
• To evaluate and compare the effect on cardiovascular risk factors of liraglutide versus placebo as add-on to existing OAD and/or insulin therapy after 26 weeks treatment in subjects with type 2 diabetes and moderate renal impairment
• To evaluate and compare safety and tolerability of liraglutide versus placebo as add-on to existing OAD and/or insulin therapy after 26 weeks treatment in subjects with type 2 diabetes and moderate renal impairment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects diagnosed with type 2 diabetes with stable diabetes treatment (unchanged medication and unchanged dose) for 90 days prior to the screening visit including:
- Monotherapy or any duo-combinations of metformin and/or SUs and/or pioglitazone. Metformin should be used with caution in subjects with moderate renal failure and must be used in accordance with local metformin labelling or guidelines.
or
- Monotherapy or any combinations of metformin and/or pioglitazone and/or basal or premix insulin. Insulin adjustments (total daily dose) ≤10% within 90 days prior to the screening visit as confirmed by the investigator are acceptable. Metformin should be used with caution in subjects with moderate renal failure and must be used in accordance with local metformin labelling or guidelines. Combination of pioglitazone and insulin should be used with caution and according to local labelling or guidelines.
• HbA1c 7–10% (both inclusive).
• Moderate renal impairment diagnosed more than 90 days prior to the screening visit and confirmed by an eGFR of 30-59 mL/min/1.73 m^2 per MDRD formula at the screening visit.
• BMI 20–45 kg/m^2 (both inclusive).
• Male or female, age 18-80 years (both inclusive).
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E.4 | Principal exclusion criteria |
• Recurrent severe hypoglycaemia or hypoglycaemic unawareness as judged by the investigator.
• Treatment with antidiabetic medication(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. Previous short-term (≤ 7 days in total) treatment with rapid- or short-acting insulin in connection with intercurrent illness is allowed at the discretion of the investigator.
• Impaired liver function, defined as ALAT ≥2.5 times upper normal limit.
• History of chronic pancreatitis or idiopathic acute pancreatitis.
• Within the past 180 days any of the following: Episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack (TIA) or other significant cardiovascular event (including e.g. arrhythmias or conduction delays on ECG).
• Heart failure defined as New York Heart Association (NYHA) class IV.
• A systolic blood pressure ≥180 mmHg or a diastolic blood pressure ≥100 mmHg.
• Rapidly progressing renal disease (e.g., acute glomerulonephritis) at the discretion of the investigator.
• Use of immunosuppressive treatment within 90 days prior to screening.
• Diagnosis or treatment for cancer in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer).
• Proliferative retinopathy or maculopathy requiring acute treatment as judged by the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c from baseline to Week 26. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Selected secondary endpoints
After 26 weeks treatment:
1. HbA1c <7.0% and no weight gain (yes/no)
2. HbA1c <7.0% and no minor or severe hypoglycaemic episodes (yes/no)
Change from baseline to week 26 in:
3. Self-measured plasma glucose (SMPG) 7-point profiles
- Mean 7-point profile
- Postprandial increments after breakfast, lunch and dinner, respectively
4. Body mass index (BMI)
Selected safety endpoints
Change from baseline to Week 26 in:
5. Renal function
- estimated glomerular filtration rate (eGFR) using the “modification of diet in renal disease (MDRD) formula”
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 26 weeks treatment
2. After 26 weeks treatment
3. From baseline to week 26
4. From baseline to week 26
5. From baseline to week 26
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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 | 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) | 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 | 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 | 2 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Poland |
Russian Federation |
Ukraine |
United Kingdom |
United States |
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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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 11 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 11 |