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 | 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 of this study is to test the hypothesis that exenatide injected twice daily is non-inferior to glimepiride given once daily before breakfast (titrated up to the maximally tolerated dose) in terms of time to treatment failure (TTF), when given as addon treatment to patients with type 2 diabetes and BMI levels of ≥ 25 kg/m2 who failed to achieve glycemic control with metformin alone.
----Study period III----- to explore the effects of different treatment options in patients with type 2 diabetes who failed to achieve HbA1c targets with metformin plus exenatide or plus glimepiride |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of Exenatide(E) and Glimepiride(G) on beta-cell function, on body weight, body mass index and waist circumference To compare E and G with respect to changes in HbA1c, to cardiovascular risk factors, on fasting and postprandial plasma glucose and blood glucose profiles. To study the efficacy and safety of different treatment options -----Specific to Study period III----- HbA1c levels during add-on treatment Proportion of patients who achieve HbA1c targets of ≤ 7.0% blood glucose profiles, proinsulin and insulin levels body weight, cardiovascular risk factors safety and tolerability |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol Sample Banking Addendum H80-EW-GWBE(1): Long-Term Treatment with Exenatide versus Glimepiride in Patients with Type 2 Diabetes Pretreated with Metformin Eli Lilly and Company has established a program, Combined Specimen Banking (CSB), to bank samples (collectively called Banking Sample) from patients enrolled in studies sponsored by Eli Lilly and Company. The banking samples are collected and banked for research to identify the genes and gene products associated with chronic diseases and/or response to clinical trial medication or other medication taking during the trial. The samples collected from the patients enrolled into study H8O-EW-GWBE (EUREXA) study will be used for research aimed at associating naturally occurring differences in the serum or plasma (proteins) or DNA (polymorphisms) with risk for diseases such as type 2 diabetes. In addition, scientific research aimed at identifying genetic or protein biomarkers related to the therapeutic response to exenatide (exendin-4) or other compounds/medications the patient is taking during the EUREXA study. As possible examples, research may look at DNA variants in the GLP-1 receptor and the response to medications like exenatide.
Protocol Addendum (2): Substudy on Body Composition, Body Fat Distribution and Adipokines Objectives: To compare the effects of exenatide and glimepiride, given as add-on treatment to metformin, on body composition (BIA), body fat distribution (MRI), and selected, non-traditional cardiovascular risk factors, after 9 months of treatment. For exploratory reasons, additional data on the effects of exenatide, glimepiride and the different treatment options given during the extention period will be collected up to the end of study.
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E.3 | Principal inclusion criteria |
[1] Patients are between 18 and 85 years of age, inclusive. [2] Patients present with type 2 diabetes based on the disease diagnostic criteria as defined by the World Health Organization (WHO). [3] Patients have been treated with diet and exercise, and a stable, maximally tolerated dose (in the opinion of the investigator) of immediate-release metformin or extended-release metformin for at least 3 months prior to screening. [4] Patients have suboptimal glycemic control as evidenced by an HbA1c between ≥6.5% and ≤ 9.0%, for whom a sulfonylurea treatment is deemed appropriate in the opinion of the investigator as a next step of diabetes treatment. [5] Patients have a body mass index ≥25 kg/m2 and < 40 kg/m2. [6] Patients have a history of stable body weight (not varying by > 10% for at least 3 months prior to screening). [7] This inclusion criterion applies to females only: Patients are not breastfeeding. And Patients of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) must fulfill all of the following criteria: o Test negative for pregnancy at the time of screening based on a serum pregnancy test. o Do not intend to become pregnant during the study. o Have practiced a reliable method of birth control (oral contraceptives or Norplant®; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy) for 3 months prior to screening. o Agree to continue to use a reliable method of birth control (oral contraceptives or Norplant®; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy) during the study, as determined by the investigator. Patients are eligible to be enrolled into Study Period III, that is the extension phase of the study, only if they meet the following additional inclusion criterion for Study Period III: [8] Patients with failure of HbA1c control (primary endpoint) as defined in Section 6.1.1 during Study Period II if failure occurs 12 months or more than 12 months prior to the projected conclusion of the study. |
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E.4 | Principal exclusion criteria |
[9] Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [10] Patients are employed by Lilly or Amylin (that is, employees, temporary contract workers, or designees responsible for the conduct of the study). Immediate family of Lilly or Amylin employees may participate in Lilly-sponsored or Lilly-managed clinical trials, but are not permitted to participate at a Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [11] Patients have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry. [12] Patients have an active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years. [13] Patients have characteristics contraindicating metformin or glimepiride use, according to product-specific label. [14] Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine ≥1.5 mg/dL (132 µmol/L) for males and ≥1.2 mg/dL (110 µmol/L) for females. [15] Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, alanine aminotransaminase (ALT), or serum glutamic pyruvic transaminase (SGPT) greater than three times the upper limit of the reference range. [16] Patients have known hemoglobinopathy or clinically significant, chronic anemia. [17] Patients have active, symptomatic proliferative retinopathy or macular edema. [18] Patients are receiving chronic treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility, including but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics. [19] Patients have severe gastrointestinal disease, including gastroparesis. [20] Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical, nasal and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening. [21] Patients have used any prescription drug to promote weight loss within 3 months prior to screening. [22] Patients have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: Insulin; Thiazolidinediones; Alpha-glucosidase inhibitors; Sulfonylurea; Meglitinides. [23] Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that renders them unable to understand the nature, scope, and possible consequences of the study or precludes them from following and completing the protocol, in the opinion of the investigator. [24] Patients fail to satisfy the investigator of suitability to participate for any other reason. Patients will be excluded from enrollment into Study Period III, that is the extension period of the study, if they meet the following additional exclusion criterion for Study Period III: [25] Patients have characteristics contraindicating thiazolidinedione use, according to product-specific label. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Period II time to treatment failure (TTF) (HbA1c measurement)
Period III o HbA1c levels body weight, cardiovascular risk factors Fasting blood glucose, blood glucose profiles, proinsulin and insulin |
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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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 22 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 133 |
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 | 3 |
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 | 3 |