E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 compare beta function (as measured by arginine stimulated insulin secretion during a hyperglycemic clamp) after 52 weeks of intensified therapy with exenatide or insulin glargine in subjects with type 2 diabetes treated with metformin.
Open ended extension to compare the beta cell function after longer term therapy with exenatide or glargine in subjects with type 2 diabetes. |
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E.2.2 | Secondary objectives of the trial |
At 52 weeks compare 1st phase, sustained insulin release, glucose measures, insulin, c-peptide, lipids, lipoproteins and markers of inflammation, coag and endothelial function. Insulin sensitivity in euglycaemic clamp test. Weight and composition. Safety and tolerability, (hypoglycemic events, bp and urinary albumin excretion rate). HOMA (insulin sensitivity and beta cell function). At cessation ; b- cell function after 4 weeks, glucose measures, insulin, lipids, lipoproteins and circulating markers at 5 weeks. HbA1c and fasting plasma glucose at 4, 8 and 12 weeks. Time before withdrawal due to loss of glucose control followed for 12 weeks.
Open ended extension. HbA1c, fasting glucose, insulin, proinsulin, c-peptide. Postprandial glucose, insulin C-peptide. Lipids, weight, HOMA. To assess the effect of treatment interruption of exenatide on safety, tolerability and anti exenatide antibodies.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
All individuals must satisfy all inclusion criteria unless appropriate approval is obtained. 1.Is between 30 and 75 years of age, inclusive. 2.Has an HbA1c of 6.6% to 9.5%, inclusive. 3.Has a body mass index of 25 kg/m2 to 40 kg/m2, inclusive. 4.Is male or if female, has a negative pregnancy test (human chorionic gonadotropin, β subunit [β hCG]) regardless of birth control method used and agrees to continue using birth control throughout the study to prevent pregnancy. 5.Has a diagnosis of type 2 diabetes and is otherwise healthy. 6.Has fasting (at least 8 h) plasma glucose <14.4 mmol/L (260 mg/dL). 7.Has blood pressure <=165/95 mmHg measured in the sitting position. 8.Has a physical examination and ECG at screening with no clinically significant abnormalities as judged by the investigator. 9.Has been treated with a stable dose of metformin for at least 3 months prior to screening. 10.Has a history of stable body weight (not varying by >10% for at least 3 months prior to screening).
Open ended extension: completed initial study, off study drug for at least 8 weeks before starting extension. |
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E.4 | Principal exclusion criteria |
Clinical significant history (organ transplant, hepatic, renal, CNS, GI, pulmonary, hematologic diseases including anemia, blood transplant, recent surgery, donated blood, low hemoglobin, CV problems) More than 3 episodes of severe hypoglycaemia within 6 months before screen Less than 2 years remission from clinical significant malignancy. Expresses apoE2 allele Known hypersensitivity to components of treatment Been in a previous exenatide study Taking excluded medications (insulin, SU, TZD, meglitinides, alpha glucosidase, gastrointestinal motility products, antineoplastics, weight loss agents, transplant medications, lipid lowering or b blockers, HRT) or any investigational drug. Received chronic systemic glucocorticoid therapy Relative to person affiliated with study Employee of Amylin or Lilly
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the treatment effect on beta-cell function as measured by the ratio of week 52 arginine-stimulated insulin secretion during a hyperglycaemic clamp, specifically the incremental AUC of insulin with respect to basal value over a 10 minute period (i.e. clamp time 290 min to 300 min) to that at baseline week -2.
Open ended extension: Stimulated beta cell function, proinsulin/insulin ratio and HOMA B. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | No |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 of last subject. |
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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 | |
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 | 9 |