| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type II Diabetes Mellitus |
|
| 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 |
|
| 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 demonstrate a dose-dependent effect of once-weekly
LY2189265 (0.1, 0.5, 1.0 and 3.0 mg) injected subcutaneously on HbA1c at 12 weeks
(change from baseline) in patients with type 2 diabetes mellitus who have discontinued metformin monotherapy or are antihyperglycemic medication-naïve. |
|
| E.2.2 | Secondary objectives of the trial |
● To evaluate dose-dependent effect of LY2189265 (0.1, 0.5, 1 and 3mg) on fasting blood glucose (FBG) at 12 weeks.
● To compare LY2189265 (0.1, 0.5, 1 and 3mg) and placebo treatment groups with respect to the following at 12 weeks:
○ HbA1c and mean daily blood glucose values.
○ beta-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S).
● To compare safety of LY2189265 (0.1, 0.5, 1 and 3mg) and placebo treatment groups at 12 weeks with respect to the following outcomes:
○ Cardiovascular (CV) system-related safety
○ Glycemia-related safety
○ Immune system-related safety
● To characterize the pharmacokinetics (PK), potential patient factors that may influence PK of LY2189265 and the relationship between LY2189265 plasma concentration, and safety and efficacy measures. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Have type 2 diabetes based on the disease diagnostic criteria (World Health Organization [WHO] classification)
[2] Are antihyperglycemic medication-naïve (diet and exercise only) or are taking metformin as monotherapy and are willing to discontinue this medication.
[3] Have completed at least 8 weeks of wash-out prior to randomization, if taking metformin.
[4] Have a qualifying HbA1c value (see protocol for criteria)
[5] Men or women, aged 18 to 75 years, inclusive.
[6] Females of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) must: (a) test negative for pregnancy at Visit 1; (b) agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; and (c) not be breastfeeding.
[7] Have a body mass index (BMI) between 23 and 40 kg/m, inclusive, for
patients who are native to, and reside in, South and/or East Asia . All other patients
must have a BMI between 25 and 40 kg/m, inclusive.
[8] Have a stable weight during the 3 months prior to Visit 1.
[9] Are well motivated, capable, and willing to:
- perform SMBG testing;
- learn how to self-inject treatment, as required for this protocol (or be assisted if visually impaired) and;
- maintain a study diary, as required for this protocol.
[10] Have given written informed consent to participate in this study |
|
| E.4 | Principal exclusion criteria |
[11] Have type 1 diabetes
[12] Are taking any glucose-lowering oral agents other than metformin within 3 months prior to Visit 1.
[13] Have been treated with a GLP-1 analog or any other incretin mimetic (e.g. liraglutide or exenatide) within the 6 months prior to Visit 1, or have been treated with insulin therapy for diabetes.
[14] Are currently taking prescription or over-the-counter medications to promote weight loss.
[15] Are receiving chronic (>2 weeks) systemic glucocorticoid therapy or have received such therapy within 4 weeks prior to Visit 1.
[16] Have a known clinically significant gastric emptying abnormality, have undergone gastric bypass surgery, or chronically take drugs that directly reduce gastrointestinal motility.
[17] Are currently taking a central nervous system stimulant.
[18] Have had any of the following cardiovascular conditions within 6 months prior to Visit 1: acute coronary syndrome, coronary heart disease treated with coronary artery bypass graft surgery or percutaneous coronary intervention (diagnostic
angiograms are permitted), heart failure, atrial or ventricular arrhythmia, pacemaker implantation, clinically significant signs of ischemic heart disease, transient ischemic attack, or cerebrovascular accident (stroke).
[19] Have poorly controlled hypertension (see protocol), renal artery stenosis, or evidence of labile BP including symptomatic postural hypotension.
[20] At Visit 1, an ECG reading considered outside the normal limits (see protocol).
[21] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine transaminase (ALT) levels >3.0 x the upper limit of the reference range at Visit 1.
[22] Have obvious clinical signs or symptoms of pancreatitis,a history of chronic pancreatitis or acute pancreatitis at Visit 1. Patients who have amylase ≥3 times the upper limit of normal and/or lipase ≥2 times upper limit of normal, as determined by the central laboratory at Visit 1, are excluded.
[23] Have a serum creatinine ≥1.5 mg/dL for men or ≥1.4 mg/dL for women, or a creatinine clearance <60 mL/minute, at Visit 1.
[24] Have uncontrolled diabetes defined as 2 or more episodes of hyperosmolar state requiring hospitalization in the 6 months prior to Visit 1.
[25] Have evidence of a significant active, uncontrolled endocrine or autoimmune abnormality.
[26] Have a history of a transplanted organ (corneal transplants allowed).
[27] 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.
[28] 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.
[29] Are investigator site personnel directly affiliated with this study and/or their immediate families.
[30] Are Lilly employees.
[31] Have received treatment within the last 30 days with a drug that has not received regulatory approval in the respective country for any indication at the time of study entry.
[32] Have participated in a study in which a medical or surgical treatment was given within 30 days prior to entry into the study.
[33] Have previously completed or withdrawn from this study after providing informed consent. |
|
| 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 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 | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | 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) | No |
| 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) | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 months | 11 |
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