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 | 9.1 |
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 |
to test the hypothesis that twice daily exenatide plus titration of basal insulin is superior to placebo plus titration of basal insulin on glycemic control as measured by change in A1C from baseline (Visit 3) to Week 30, with or without oral antihyperglycemic medications (OAMs) in adult subjects with T2DM who are suboptimally controlled (A1C ≥7.1% and ≤10.5%). |
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E.2.2 | Secondary objectives of the trial |
to compare the efficacy and safety of exenatide to placebo when added to basal insulin glargine with or without OAMs with respect to: • percentage of subjects with A1C ≤7.0% and A1C ≤6.5% at 30 weeks; • change from baseline in fasting glucose; • 7-point self-monitored blood glucose (SMBG) profiles and mean blood glucose (BG) measurement based on 7-point SMBG; • change from baseline in fasting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides; • change from baseline in body weight (kg); • change from baseline in waist circumference (cm); • change from baseline in insulin dose (24-hour total international units [IU] and total units/kg body weight); • change from baseline in seated systolic (SBP) and diastolic blood pressure (DBP); • safety, as measured by: o self-reported hypoglycemic episodes; o treatment-emergent adverse events (TEAEs); |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Have T2DM [2] Are at least 18 years of age [3] Have been taking basal insulin glargine at a dose of ≥20 units/day for at least 3 months prior to Visit 1 [4] Have been receiving glargine alone or in combination with one of the following OAM regimens for the 3 months prior to Visit 1:metformin,pioglitazone, a combination of metformin and a pioglitazone at a stable dose for 6 weeks prior to Visit 1 and do not meet exclusion criteria 11. [5] Have an A1C ≥7.1% and ≤10.5%. [6] Have a body mass index (BMI) ≤45 kg/m2. [7] Show no evidence of cardiovascular disease as determined by a normal electrocardiogram (ECG) [8] Have a history of stable body weight [9] Liver enzyme tests (ALT, AST) are not greater than 1.5 times the upper limit of the reference range [10] Are female subjects with serum creatinine level ≤1.4 mg/dL or male subjects with serum creatinine level ≤1.5 mg/dL. |
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E.4 | Principal exclusion criteria |
[11] Are currently taking a dose or combination of OAM that is not allowed with concurrent use of insulin glargine per local product label [12] Have taken any glucose-lowering medications not included in Inclusion Criteria [3] and [4] in the 3 months prior to Visit 1 for more than 1 week or within 1 month of screening. [13] Have taken any insulin other than glargine within the 3 months prior to Visit 1 for more than 1 week or within 1 month of screening [14] Have had more than one episode of major hypoglycemia, within 6 months prior to Visit 1 [15] Are pregnant or intend to become pregnant during the course of the study or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable. [16] Women who are breastfeeding. [17] presence of clinically significant hematologic, oncologic, renal, cardiac, hepatic, gastrointestinal disease, or any other serious disease [18] Have a history of renal transplantation or receiving dialysis [19] Are subjects with a malignancy (see protocol for specifics) [20] Have contraindication or known hypersensitivity or allergy to exenatide or to any of the product components [21] Have used a drug for weight loss within 3 months prior to Visit 1 for more than 1 week or within 1 month of screening [22] Are currently on a supervised weight-loss program [23] Have had a blood transfusion or severe blood loss within 3 months prior to Visit 1 or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other condition known to interfere with the A1C methodology. [24] Are receiving chronic systemic glucocorticoid therapy or have received such therapy within the 8 weeks immediately preceding Visit 1. [25] Have an irregular sleep/wake cycle [26] Have any other condition that renders the subject unable to understand the nature, scope, and possible consequences of the study, [27] Have received treatment within 30 days before Visit 1 with a drug that has not received regulatory approval for any indication at the time of study entry. [28] Are investigator site personnel directly affiliated with this study and/or their immediate families. [29] Are employed by Lilly or Amylin Pharmaceuticals, Inc. [30] Have previously completed or withdrawn from this study after signing the ICD. [31] If on metformin and have contraindication to metformin use [32] If on metformin, have had a radiologic contrast study performed within 48 hours prior to Visit 1. [33] If on pioglitazone, have a contraindication to pioglitazone including NYHA Class II-IV CHF or are on a dose of pioglitazone that is contraindicated with insulin in that country. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary analysis variable is the change in A1C, and the primary analysis set is FAS. The conclusion for the primary analysis will be based on the pvalue for the test of treatment effect at 30 weeks. |
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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 | 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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 11 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 1 |