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 |
The primary objective of this study is to determine whether exenatide given subcutaneously twice daily provides better HbA1c control, with minimal weight gain, than basal insulin given subcutaneously once daily for six months in patients with type 2 diabetes not adequately controlled using a combination of oral anti-diabetic therapy and are a higher risk population (see section 4.1.1) as measured by the proportion of patients who have achieved HbA1c ≤ 7.4% with minimal weight gain (≤ 1kg). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to compare exenatide and insulin glargine with respect to: •Proportion of patients who have achieved HbA1c ≤ 7.4% and ≤ 0.5kg weight gain •Fasting serum glucose (FSG) •The proportion of patients achieving: oHbA1c ≤ 7.4% oHbA1c < 7% oHbA1c < 6.5% •7 point self monitoring blood glucose (SMBG) profile •Changes in cardiovascular risk parameters: oBMI (body mass index), waist circumference, waist/hip ratio. Weight change in kg and % plus the proportion of patients achieving 5% and 10% weight change. oSystolic and diastolic BP (blood pressure). oLipid profile. •Hypoglycaemia rate per patient (adjusted for 30 days), incidence and severity •Noctural hypoglycaemia •Safety and Tolerability •Patient reported Quality of Life •Healthcare Resource Utilisation
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients are eligible to be included in the study only if they meet all of the following criteria: [1] Present with type 2 diabetes based on the disease diagnostic criteria, and are currently being treated with the following: Dual or triple oral therapy – on a stable combination and dose for at least 3 months. Patients will continue on their oral therapy. [2] HbA1c between 7.5% and 9.5%. [3] Present with any one of the cardiovascular risk factors as defined in Section 4.1.1. Disease Diagnostic Criteria. [4] BMI >27. [5] Are at least 30 years of age and less than 75 years of age. [6] Negative pregnancy test for women of childbearing potential (see exclusion criteria).
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: [7] Investigators, site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted. [8] Are employed by Lilly or Amylin (that is, employees, temporary contract workers, or designees responsible for conducting the study). Immediate family of Lilly or Amylin employees may participate in Lilly-sponsored 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. [9] Patients who 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. [10] Have cardiac disease that is Class III or IV (see attachment GWBG.7). [11] Uncontrolled hypertension (systolic ≥ 180mmHg, diastolic ≥ 105mmHg). [12] Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than or equal to 135 µmol/L for males and greater than or equal to 110 µmol/L for females. [13] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or ALT/SGPT greater than three times the upper limit of the reference range as defined by the local laboratory. [14] Have known haemoglobinopathy or chronic anaemia. [15] Have known proliferative retinopathy. [16] Have known metabolic acidosis. [17] Patients who would be otherwise excluded due to the label of the concomitant oral therapy. [18] Female patients who are breastfeeding. AND Female patients of childbearing potential (not surgically sterilised and between menarche and 1-year postmenopausal) who must fulfill all of the following criteria: o Test negative for pregnancy at the time of screening based on a urine 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. [19] Receive chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to Visit 1. [20] Have had more than one episode of severe hypoglycaemia (defined as requiring assistance of a third party due to disabling hypoglycaemia) within 6 months prior to entry into the study. [21] Have participated in an interventional medical, surgical, or pharmaceutical study (a study in which a medical or surgical treatment was given) within 30 days prior to entry into the study. [22] Have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the patient from following and completing the protocol. [23] Treatment with the following medications: • Insulin as outpatient therapy within last 3 months. • Meglitinides, or acarbose within the last 3 months. • Regular use of any drugs that directly affect gastrointestinal motility (see attachment GWBG.8). • Any previous (study) therapy with exenatide or GLP-1 analogue. • Anti-obesity agent use within the last 3 months. [24] History or presence of bulimia or laxative abuse. [25] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the proportion of patients achieving HbA1c ≤ 7.4% with minimal weight gain (≤ 1kg). |
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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 | Information not present in EudraCT |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | No |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |