E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012601 |
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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 assess and compare the effect on glycaemic control as measured by HbA1c of once daily administration of three doses of liraglutide in combination with glimepiride versus glimepiride monotherapy versus rosiglitazone and glimepiride combination therapy in subjects with type 2 diabetes |
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E.2.2 | Secondary objectives of the trial |
To assess and compare the effect on body weight To assess and compare the effect on glycaemic control fasting plasma glucose FPG , 7-point plasma glucose profiles self measured To assess and compare 946;-cell function Fasting insulin, fasting C-peptide, fasting pro-insulin and glucagon . The homeostasis model assessment HOMA 1 will be used To assess and compare lipid profiles total cholesterol TC , low density lipoprotein cholesterol LDL-C , very low density lipoprotein cholesterol VLDL-C , high density lipoprotein cholesterol HDL-C , triglyceride TG , free fatty acid FFA , apolipoprotein B ApoB To assess and compare the effect on blood pressure |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
6.2 Inclusion Criteria 1. Informed consent IC obtained before any trial-related activities trial-related activities are any procedures that would not have been performed during normal management of the subject . 2. Subjects diagnosed with type 2 diabetes and treated with OAD s for at least 3 months. 3. HbA1c 61485; 7.0-11.0 both inclusive in subjects on OAD monotherapy 61485; 7.0-10.0 both inclusive in subjects on OAD combination therapy 4. Age 18 80 years, both inclusive, as allowed according to local guidelines for glimepiride and rosiglitazone treatment . 5. Body mass index BMI 61603; 45.0 kg/m2. 6.4 Randomisation Criteria 1. Daily use of 4 mg glimepiride for at least two weeks. 2. Mean FPG of 7.0-12.8 mmol/L both incl. 126-230 mg/dL both incl. measured by the Investigator, at the clinic, by use of a glucose meter. A mean of two consecutive measurements using two strips should be used. If FPG at the day of randomisation is outside the above limits, randomisation may be postponed once within the limits of the visit window between Visit 2 and Visit 3. |
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E.4 | Principal exclusion criteria |
6.3 Exclusion Criteria 1. Treatment with insulin within the last three months prior to the trial except for short-term treatment with insulin in connection with intercurrent illness at the discretion of the Investigator . 2. Impaired liver function, defined as ALAT 61619; 2.5 times upper limit of normal ULN one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive . 3. Subjects known to be Hepatitis B antigen or Hepatitis C antibody positive. 4. Impaired renal function defined as serum-creatinine 61619; 125 61549;mol/L 61619; 1.4 mg/dL for males and 61619; 110 61549;mol/L 61619; 1.3 mg/dL for females one retest analysed at the central laboratory within a week permitted with the result of the last sample being conclusive . 5. Clinically significant active cardiovascular disease including history of myocardial infarction within the past 6 months and/or heart failure New York Heart Association NYHA class I-IV at the discretion of the Investigator see Appendix C . 6. Proliferative retinopathy or maculopathy requiring acute treatment as judged by the Investigator. 7. Uncontrolled treated/untreated hypertension systolic blood pressure 61619; 180 mmHg and/or diastolic blood pressure 61619; 100 mmHg . 8. Cancer except basal cell skin cancer or squamous cell skin cancer or any clinically significant disease or disorder, except for conditions associated to type 2 diabetes, which in the Investigator s opinion could interfere with the results of the trial. 9. Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator. 10. Known or suspected allergy to trial products or related products. 11. Use of any drug except for OADs , which in the Investigator s opinion, could interfere with the glucose level e.g. systemic corticosteroids . 12. The receipt of any investigational drug within four weeks prior to this trial. 13. Previous participation in the randomised phase of this trial. Re-screening is allowed once within the limits of the recruitment period. 14. Known or suspected abuse of alcohol or narcotics. 15. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation. 16. Females of child bearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant or not using adequate contraceptive methods adequate contraceptive measures as required by local law or practise . 17. Any contraindications to glimepiride or rosiglitazone according to local requirements . |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint HbA1c |
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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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | 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.8.5 | 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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 |
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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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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 | 1 |
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 | 1 |