| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Overweight/Obese Type 2 Diabetic Patients Not Adequately Controlled with Metformin |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
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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 |
| The primary objective is to demonstrate, after 52 weeks (1 year) of treatment, the non-inferiority of rimonabant 20 mg od versus glimepiride od in reducing HbA1c in overweight/obese patients with type 2 diabetes not adequately controlled with metformin at a stable dose (≥ 1500mg/day) for at least 3 months. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- To assess the effect of rimonabant in comparison to glimepiride after 52 weeks (1 year) of treatment on:
- Body weight.
- HDL-Cholesterol.
- Waist circumference.
- Triglycerides (TG).
- Other markers of glycemic control (fasting glucose, fasting-insulin, C-peptide).
- To evaluate the long-term safety and tolerability of rimonabant in comparison with glimepiride in patients with type 2 diabetes not adequately controlled with metformin
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Male or female patients with legal age.
- BMI > 27 kg/m².
- Type 2 diabetes as defined by WHO criteria (26) (diagnosis was based on fasting venous plasma glucose concentration ≥ 7.0 mmol/L or 2-h post-glucose load venous plasma glucose ≥ 11.1 mmol/L) only treated with metformin for at least 6 months and with a stable dose of metformin ≥ 1500 mg/day for at least three months.
- HbA1c ≥ 7% and ≤ 9% at screening Visit.
- Patients able to perform self monitoring blood glucose as confirmed at baseline Visit
|
|
| E.4 | Principal exclusion criteria |
Exclusion criteria relating to methodology
- Weight loss > 5 kg within three months prior to screening Visit.
- Patients with conditions/concomitant diseases making them non evaluable for the efficacy assessment:
- Presence of any clinically significant endocrine disease according to the Investigator (euthyroid patients on replacement therapy will be included if the dosage of thyroxine is stable for at least three months prior to screening Visit).
- Presence of type 1 diabetes.
- Presence of any severe medical or psychological condition or chronic conditions/infections that in the opinion of the Investigator would compromise the patient’s safety or successful participation in the study.
- Presence or history of cancer within the past five years with the exception of adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer.
- Previous participation in a clinical study with rimonabant.
- History of previous treatment with sulphonylurea(s).
NB: This previous treatment will be allowed if there was no prescription of a sulphonylurea within 1 year prior to screening visit and the duration was less than 3 months. Cessation of this treatment should not have been linked to safety purpose.
- Administration of other investigational drugs within 30 days prior to screening Visit.
- Absence of effective medical contraceptive method for females of childbearing potential.
- Related to previous or concomitant medications that could bias evaluation of primary and secondary endpoints:
- Within 6 months prior to screening Visit and/or between the screening and the baseline Visits:
- Administration of any oral antidiabetic drugs other than metformin (i.e.; metiglinides, thiazolidinediones, alpha-glucosidase inhibitors, DPP-a inhibitors, GLP-1 agonists) and/or insulin (for sulphonylurea treatment see above).
- Within 3 months prior to screening Visit and/or between the screening and the baseline Visits:
- Administration of anti-obesity drugs (sibutramine, orlistat).
- Administration of other drugs for weight reduction (e.g., phentermine, amphetamines).
- Administration of thyroid preparations or thyroxine (except in patients on stable replacement therapy).
- Within 2 months prior to screening Visit and/or between the screening and the baseline Visits:
- Administration of systemic long-acting corticosteroids.
- Prolonged use (more than one week) of other systemic corticosteroids.
- Change in the lipid lowering treatment.
N.B.: Optimal dosing for lipid lowering therapies (if any) should be achieved at least 2 months prior to screening and therefore, changes in lipid-lowering therapies or doses are discouraged after screening. However, changes can be made if clinically indicated. If such a change in lipid-lowering therapies is expected/planned at the time of the screening Visit (or prior to the baseline Visit), the patient should not be randomized.
- Within 30 days prior to screening Visit and/or between the screening and the baseline Visits:
- Administration of herbal preparations for weight reduction
- Related to laboratory findings:
- Endogeneous insulin production as measured by a fasting C-peptide < 1.0 ng/mL.
- Abnormal serum thyrotropin (TSH) levels at screening Visit.
- Positive test for hepatitis B surface antigen and/or hepatitis C antibody at screening Visit.
- Positive urine pregnancy test in females of childbearing potential at screening and baseline Visits.
- Any relevant abnormality interfering with the efficacy or the safety assessments during the study drug administration.
- Patients considered by the Investigator unsuitable candidates to receive an investigational drug.
- Refusal or inability to give informed consent to participate to the study.
- Presence of any other condition (e.g. geographic, social…) actual or anticipated, that the Investigator feels, would restrict or limit the patient’s participation for the duration of the study.
Exclusion criteria related to glimepiride
- Pregnancy or breast feeding.
- Severe renal or hepatic function disorders.
- Known hypersensitivity to glimepiride.
- History of diabetic ketoacidosis with or without coma
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Absolute change in HbA1c from baseline to 52 weeks (1year).
Secondary analyses of the primary criteria
- Absolute change in HbA1c from baseline over time by visit.
- Percentage of patients with HbA1c < 7% at the end of the study on Week 52.
- Percentage of patients with HbA1c ≤ 6.5% at the end of the study on Week 52
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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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| 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 | 7 |
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