| 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 | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
|
| 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 exenatide once weekly is superior to metformin, sitagliptin, and pioglitazone in HbA1c reduction at 26 weeks compared to baseline, in drug-naive patients with type 2 diabetes who are inadequately treated with diet and exercise. |
|
| E.2.2 | Secondary objectives of the trial |
To compare exenatide once weekly to metformin, sitagliptin, and pioglitazone over 26 weeks with respect to:
• the proportion of patients achieving HbA1c <or=7% and < or=6.5%
• change in fasting serum glucose
• change in body weight
• 7-point self-monitored blood glucose (SMBG) profile
• change in serum lipids
• incidence of hypoglycemic events
• change in systolic and diastolic blood pressure
• safety and tolerability
• health outcomes
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol Sample Banking Addendum H8O-MC-GWCH(1):
Eli Lilly and Company has established a program, Combined Specimen Banking (CSB), to bank samples from patients enrolled in studies sponsored by the company. There is an anonymization process. Patient participation is volontary. The choice not to participate in banking will not be considered a protocol violation. The Banked Samples are collected and banked for research to identify the genes and/or gene products and/or biochemical markers associated with diseases and/or response to clinical trial medication or other medication taken during the trial. For example, the samples collected from the patients may be used for research aimed at associating naturally occurring differences in the serum or plasma (proteins) or DNA (polymorphisms) with risk for diseases such as type 2 diabetes. In addition, scientific research may be aimed at identifying genetic or protein biomarkers related to the therapeutic response to exenatide or other compounds/medications the patient is taking during this study. As possible examples, research may look at DNA variants in the GLP-1 receptor and the response to medications like exenatide.
Protocol Sample Storage Addendum H8O-MC-GWCH(2.1):
The primary objective is to collect and store blood for research into biomarkers associated with type 2 diabetes mellitus and treatment with exenatide. |
|
| E.3 | Principal inclusion criteria |
Patients, males or females, 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 as described by the World Health Organization (WHO) and are treated with diet and exercise alone.
[2] Are at least 18 years of age at screening
[3] Have suboptimal glycemic control as evidenced by an HbA1c between 7.1% and 11.0%, inclusive
[4] Have a body mass index (BMI) of 23 kg/m2 to 45 kg/m2, inclusive
[5] Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening).
[6] This inclusion criterion applies to females of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopause) only.
○ Are not breastfeeding.
○ Test negative for pregnancy at the time of screening based on a blood serum pregnancy test.
○ Intend not to become pregnant during the study.
○ Have practiced a reliable method of birth control for at least 6 weeks prior to screening.
○ Agree to continue to use a reliable method of birth control during the study, as determined by the investigator.
|
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
[7] Are Lilly, Amylin, or Alkermes employees.
[8] 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.
[9] Have had a clinically significant history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study, including myocardial infarction, clinically significant arrhythmia, unstable angina, moderate to severe congestive heart failure (New York Heart Association Class III or IV [CCNYHA 1994]), coronary artery bypass surgery, or angioplasty; or is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
[11] regarding local label exclusions for cardiac failure.
[10] Have any contraindication for the study drug (exenatide, metformin, sitagliptin, or pioglitazone, or the excipients contained in these agents) to which they may be assigned.
[11] Have had poorly controlled blood pressure within the last 4 weeks.
[12] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, alanine aminotransferase (ALT), or serum glutamic pyruvic transaminase (SGPT) greater than 2.5 times the upper limit of the reference range.
[13] Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine > or=1.5 mg/dL for males and > or=1.2 mg/dL for females.
[14] Have active or untreated malignancy, or have been in remission from clinically significant malignancy for less than 5 years.
[15] Have known hemoglobinopathy or chronic anemia (hemoglobin concentration <115 g/L for males, <105 g/L for females).
[16] Have had more than 2 episodes of major hypoglycemia within 6 months prior to screening.
[17] Patients with a history of severe GI disorder (e.g., gastroparesis)
[18] Patients with a history of acute or chronic pancreatitis.
[19] Are known to have active proliferative retinopathy.
[20] Have been treated within 8 weeks of screening with systemic glucocorticoid therapy by oral, intravenous, or intramuscular route, or are regularly treated with potent, inhaled or intranasal steroids that are known to have a high rate of systemic absorption. Exceptions to this criterion include patients who are receiving chronic glucocorticoid therapy for corticotropic hypopituitary deficiency (e.g., Addison disease).
[21] Have been treated with drugs that promote weight loss (e.g., Xenical® [orlistat], Meridia® [sibutramine], Acomplia® [rimonabant], Acutrim® [phenylpropanolamine], or similar over-the-counter medications) within 3 months of screening.
[22] Have been treated with any antidiabetic agent for more than 7 days within 3 months prior to screening.
[23] Have had an organ transplant.
[24] Have any exclusion criteria required by local law.
[25] Have previously completed or discontinued study drug in this study, withdrawn from this study or any other study investigating exenatide once weekly.
[26] 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.
[27] Are currently enrolled in any other clinical study.
[28] Have any other condition that renders them unable to understand the nature, scope, and possible consequences of the study or precludes them from following and completing the protocol, in the opinion of the investigator.
[29] Fail to satisfy the investigator of suitability to participate for any other reason.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in HbA1c from baseline to week 26. |
|
| 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 | No |
| 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 | Information not present in EudraCT |
| 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) | 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 39 |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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