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 | 10012601 |
E.1.2 | Term | 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 demonstrate that the glycemic control of the high dose of LY2189265 selected at the Decision Point is noninferior to that of sitagliptin at 12 months (52 weeks), as measured by HbA1c change from baseline in patients with type 2 diabetes on metformin. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that • the high dose of LY2189265 is superior to placebo at 6 months • the high dose of LY2189265 is superior to sitagliptin at 12 months • the low dose of LY2189265 is superior to placebo at 6 months • the low dose of LY2189265 is noninferior to sitagliptin at 12 months • the low dose of LY2189265 is superior to sitagliptin at 12 months
Additional secondary objetives are included and outlined in the protocol. |
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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 |
Test Meal; Protocol Addendum H9X-MC-GBCF(1); ; Version 1; 2008-04-15. Objective: To evaluate the effect of once-weekly LY2189265 compared to sitagliptin and placebo after a standard test meal given at randomization (Visit 4), Month 1 (Visit 6), and Month 6 (Visit 9) with respect to: • fasting blood glucose (FBG), • postprandial blood glucose (PPBG), and • insulin concentrations.
Sample Banking; Protocol Addendum H9X-MC-GBCF(12; ; Version 1; 2008-04-15. Objective: Banked Samples are collected and banked for research to identify the genes, 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, in Study H9X-MC-GBCF, the samples collected from patients will be used to identify genetic and/or protein and/or biochemical markers related to LY2189265 and/or type 2 diabetes. The banked samples are anonymized.
Sample Storage; Protocol Addendum H9X-MC-GBCF(3); ; Version 1; 2008-04-15. Objective: To collect and store samples of blood, plasma, and serum for future research to evaluate genetic variants and biomarkers that may be associated with type 2 diabetes mellitus and/or treatment with LY2189265. Stored samples will retain the patient identifier. Samples will be stored for a maximum of 5 years after the last patient visit for the study.
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E.3 | Principal inclusion criteria |
[1] Have type 2 diabetes for at least 6 months prior to entering the trial [2] Are treated with diet and exercise, are taking metformin as monotherapy or in combination with another OAM, or are taking another OAM as monotherapy [3] Have an HbA1c value of ≥7.0% to ≤9.5% [4] Men or women who are between the ages of 18 to 75 years [5] Females of childbearing potential (not surgically sterilized & between menarche & 1-year postmenopausal) must test negative for pregnancy at Visit 1: agree to use a reliable method of birth control; & not be breastfeeding [6] Have a body mass index (BMI) between 25 and 40 kg/m2 [7] Have a stable weight during the 3 months prior to Visit 1 [8] Well motivated, capable, and willing to perform SMBG testing; learn how to self-inject treatment (or with assistance for those with physical limitations); & maintain a study diary [9] Have given written informed consent to participate in this study |
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E.4 | Principal exclusion criteria |
[10] Have known type 1 diabetes [11] Have been treated with a GLP-1 analog within 6 months prior to Visit 1 or are being treated with insulin [12] Have a known clinically significant gastric emptying abnormality, have undergone gastric bypass (bariatric) surgery, or chronically take drugs that directly reduce gastrointestinal motility [13] Are currently taking prescription or over-the-counter medications to promote weight loss [14] Have had a listed cardiovascular event (see protocol) within 6 months prior to Visit 1 or between Visits 1 and 4 [15] Have poorly controlled hypertension (as defined in protocol), renal artery stenosis, or evidence of labile blood pressure including symptomatic postural hypotension [16] At Visit 1, an ECG reading considered outside the normal limits & relevant for interpretation or indicating cardiac disease; aberrant, blocked, or impaired propagation; and clinically significant signs of ischemic heart disease [17] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, a history of chronic pancreatitis or idiopathic acute pancreatitis, or ALT levels >3.0 times the upper limit of the reference range at Visit 1 [18] Have a serum creatinine ≥1.5 mg/dL, or a creatinine clearance <60 ml/minute at Visit 1, which would contraindicate the use of metformin per the local label [19] Have uncontrolled diabetes defined as more than 2 episodes of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to Visit 1 [20] Have evidence of a significant active, uncontrolled endocrine or autoimmune abnormality [21] Have a history of a transplanted organ (corneal transplants [keratoplasty] allowed) [22] Are receiving chronic (>2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations) or have received such therapy within 4 weeks immediately prior to Visit 1 [23] Have an active or untreated malignancy or have been in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years [24] Have any other condition (such as, known drug or alcohol abuse or psychiatric disorder) that may preclude the patient from following and completing the protocol [25] Have any contraindication, known allergy, or hypersensitivity to metformin, sitagliptin, or excipients contained in these products [26] Are currently taking a central nervous system stimulant [27] Are investigator site personnel directly affiliated with this study and/or their immediate families [28] Are Lilly employees [29] 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. [30] Have participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to entry into the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure of this study is HbA1c change from baseline at 12 months |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | 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) | Yes |
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 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |