| 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.1.2 | Term | Diabetes |
|
| 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 estimate the difference in change in HbA1c from the randomization visit (visit 2) to endpoint (30 weeks) between 2 regimens: BET (basal insulin Glargine, Exenatide BID and metformin) and BBT (basal insulin Glargine,, bolus insulin insulin TID and metformin) in subjects with type 2 diabetes and inadequate glycemic control (HbA1c > 7.0%) pretreated with basal insulin Glargine in combination with metformin or in combination with metformin and sulfonylurea (SU). |
|
| E.2.2 | Secondary objectives of the trial |
To compare the efficacy and safety between the BET and BBT regimens with respect to:
•Percentage of subjects with HbA1C ≤7.0 % with minimum weight gain and with HbA1C ≤6.5 % with minimum weight gain (≤1kg)
• Percent of subjects with HbA1c ≤7.0 % and ≤6.5 %
• FBG
•7-point self-monitored blood glucose (SMBG) profiles and daily mean blood glucose (BG) based on the 7-point SMBG profile
•Fasting Glucagon
•Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides
•Body weight and BMI
•Waist and hip circumference
•Insulin dose
• SBP and DBP
• Safety as measured by
o self-reported hypoglycemic episodes and incidence of major hypoglycemic events
oTEAEs
oanti-Exenatide antibodies
•Patient reported quality of life as measured by the short form of the IWQOL-Lite
• Patient satisfaction with treatment as measured by the DTSQ) status and change versions
•Resource use with regards to Adverse Events and frequency of non-protocol required SMBG.
|
|
| 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)
[2]Are at least 18 years of age
[3]Have been taking a basal insulin Glargine, at dose of ≥20 units/day, for at least 3 months prior to visit 1
[4]Have been taking basal insulin Glargine at dose of ≥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 ≤10.0%.
[6]Have a body mass index (BMI) between ≥25 and ≤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).
|
|
| 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]
[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 systemic glucocorticoid therapy 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 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 investigator’s 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)
[28]Have previously completed or been withdrawn from this study after enrollment.
[29]If on metformin and have contraindication to metformin use, including known metabolic or lactic acidosis, or any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis.
[30]Have had a radiologic contrast study performed within 48 hours prior to visit 1.
[31] have any exclusion required by local law
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy measure will be the change in HbA1c from baseline (Visit 2) to 30 weeks. |
|
| 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 | 15 |
| 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 | |
| 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 | 11 |
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