| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 | 10012594 |
|
| 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 estimate the difference in change in HbA1c from randomization visit (Visit 2) to endpoint (30 weeks) between two regimens: BET (basal insulin Glargine and Exenatide) and BBT (basal insulin Glargine and bolus insulin insulin lispro TID) in subjects with type 2 diabetes and inadequate glycemic control, pretreated by basal insulin Glargine in combination with metformin alone or in combination of metformin and sulfonylurea. Non-inferiority will be concluded if the upper limit of the 95%-confidence interval (CI) for the treatment group difference (BET minus BBT) is <0.4% and <0.3%, respectively |
|
| E.2.2 | Secondary objectives of the trial |
| to determine the clinical outcomes of the different treatment regimens in terms of: &#56256;&#56320; efficacy in terms of glycemic control, and other aspects e.g. body weight and insulin dose &#56256;&#56320; safety in terms of adverse events, hypoglycemia events and anti-Exenatide antibodies &#56256;&#56320; effects on cardiovascular parameters. &#56256;&#56320; Health outcomes &#56256;&#56320; Resource utilization |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| [1] Have T2DM (as defined by World Health Organization [WHO] classification; see Protocol Attachment GWDM.3). [2] Are at least 18 years of age. [3] Have been taking a basal insulin Glargine, at dose of &#8805;20 units/day, for at least 3 months prior to visit 1. [4] Have been taking basal insulin Glargine at dose of &#8805;20 units/day, in combination with 1 of the following OAM regimens, for at least 3 months prior to visit 1 [a] Metformin or immediate-release metformin or extended-release metformin alone at a maximum tolerated and stable dose with no less than 500 mg/day for at least 6 weeks prior to visit 1. Or [b] Metformin or immediate-release metformin or extended-release metformin at a maximum tolerated and stable dose with no less than 500 mg/day for at least 6 weeks prior to visit 1 and sulfonylurea at a stable dose for 6 weeks prior to visit 1. [5] Have an HbA1C >7.0% and &#8804;10.0%. [6] Have a body mass index (BMI) between &#8805;25 and &#8804;45 kg/m2. [7] Have a history of stable body weight (not varying by >10% for at least 3 months prior to visit 1. [8] Liver enzyme tests (alanine aminotransferase [ALT]; aspartate aminotransferase [AST]) are not greater than three times of the upper limit of the reference range (as defined by the Lilly-designated laboratory). [7] Pazienti con indici di funzione epatica (alanina aminotransferasi [ALT]; aspartato aminotransferasi [AST]) non superiori di 3 volte il limite superiore del range di normalita`. (Se i valori sono 1.5 volte superiori, ma comunque inferiori di 3 volte il limite superiore di normalita`, le transaminasi dovranno essere ripetute con un intervallo di 6 mesi). [8] Donne non in gravidanza oppure, se in eta` fertile, che adottino nel periodo dello studio un metodo sicuro di contraccezione come determinato dal medico. |
|
| E.4 | Principal exclusion criteria |
| [9] Are currently taking OAM that is not described above and not allowed with concurrent use of insulin per local product label. [10] Have taken more than 1 week within 1 month prior to the visit 1 any glucose-lowering medications not included in inclusion criteria [3] and [4] (for example those not approved for use with insulin, rosiglitazone, rimonabant, acarbose, miglitol, pramlintide, repaglinide, nateglinide or DPP-4 inhibitors, or pioglitazone) either alone or in combination formulations, or have used a drug for weight loss (for example, prescription drugs such as orlistat, sibutramine, phenylpropanolamine, rimonabant or similar over-the-counter medications) [11] Have taken any insulin other than Glargine within the 3 months prior to visit 1 for more than 1 week. [12] Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, and inhaled preparations) within 4 weeks prior to the visit 1 [13] Have had a clinically significant history of cardiac disease with functional status that is Class III or IV (New York Heart Association Class III or IV) (see Protocol Attachment 5) or considered by the investigator to be exclusionary. [14] Have had more than 1 episode of major hypoglycemia, as defined in the Abbreviations and Definitions section, within 6 months prior to visit 1 [15] Female subjects with a positive pregnancy test and/or intending to become pregnant or sexually active and not using birth control throughout the study to prevent pregnancy. [16] Women who are breastfeeding. [17] Have any of the following concomitant diseases: presence of clinically significant hematologic, oncologic, renal (or have creatinine clearance below 30 ml/min), cardiac, hepatic or gastrointestinal disease or any other serious disease considered by the investigator to be exclusionary. [18] Have fasting triglycerides levels > 500mg/dl ( >5.64mmol/l) [19] Have a history of renal transplantation or are currently receiving renal dialysis. [20] Have a history of confirmed pancreatitis [21] 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. [22] Have contraindication or known hypersensitivity or allergy to Exenatide or to any of the product components (including prior withdrawal of Exenatide therapy after experiencing adverse events). [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 HbA1c methodology. [24] Have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the subject from following and completing the protocol, according to the investigators judgment. [25] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [26] Are investigator site personnel directly affiliated with this study and/or their immediate families.Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [27] Are employed by Lilly or Amylin Pharmaceuticals, Inc.(Amylin) (that is, employees, temporary contract workers, or designees responsible for conducting the study). [28] Have previously completed or been withdrawn from this study after enrollment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy measure will be the change in HbA1c from baseline |
|
| 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 | 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 91 |
| 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 | 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
| |
| 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 | 11 |
| 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 | 11 |
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