Type 2 diabetes mellitus MedDRA version: 9.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus
Conditions
Interventions
Product Name: LY2428757 for Injection, 5 mg
Pharmaceutical Form: Powder for solution for injection
Current Sponsor code: LY2428757
Other descriptive name: GLP-PEG, GLP-1 Analog V PEG, GLP PEG 40
Conce
Sponsors
Eli Lilly and Company, Indianapolis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Have T2DM for at least 6 months before entering the trial based on the disease diagnostic criteria (World Health Organization [WHO]) classification (see Protocol Attachment GECD.3). - Are currently being treated with diet and exercise therapy consistent with the local standards of medical care, in the opinion of the investigator. - Patients may be treated with diet and exercise alone or in combination with a stable dose, at least 1000 mg/day, of metformin for at least 2 months before Visit 1. - Have an HbA1c value of 7% to 10% , inclusive, at Visit 1 and a fasting glucose =15 mmol/L (270 mg/dL) at Visit 2. - Men or women who are between the ages of 18 to 70 years, inclusive. - Women of child-bearing potential must test negative for pregnancy at the time of Visit 1 and agree to abstain from heterosexual intercourse for the duration of the study, or use 2 effective forms of birth control during the study, including at least 1 of the following: tubal ligation (sterilization), partner's vasectomy, intrauterine device, or hormonal treatment (combination oral contraceptives, transdermal patch, injectables, implantables, or vaginal ring). Other forms of contraception that can be combined with 1 of the above are male latex condom with or without spermicide, diaphragm with spermicide, cervical cap with spermicide, or vaginal sponge. - Have a body mass index (BMI) between 25 and 40 kg/m2, inclusive at Visit 1. - Weight stable (±5 kg) during the 3 months before Visit 1 (by patient self-report). - In the investigator’s opinion, are well motivated, capable, and willing to • perform self monitoring of blood glucose (SMBG) • complete study diary/ies, as required for this protocol • are receptive to continuing their prestudy diet, activity levels, and follow simple dietary advice as appropriate • comply with the required study and dosing visits. - Have given written informed consent to participate in this study in accordance with local regulations and the Ethical Review Board (ERB) governing the study site. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Use of insulin or any antidiabetic agent other than metformin during the 2 months before Visit (V) 1. - In the opinion of the investigator, have a gastrointestinal disease that significantly impacts gastric empting or motility or have undergone bariatric surgery. - Have had more than 1 episode of severe hypoglycemia, as defined in the Abbreviation and Definitions section of this protocol, within 6 months before entry into the study, or is currently diagnosed with having hypoglycemia unawareness. - Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months. -Are currently taking prescription or over-the-counter medications to promote weight loss. - Have a history of acute or chronic pancreatitis or elevation of serum lipase (greater than 2 times the upper limit of normal). -Women who are breastfeeding. - In the last 2 years, have known or suspected cardiac autonomic neuropathy, based on clinical signs, symptoms, or appropriate diagnostic testing. - Have cardiac disease with functional status that is NYHA Class II, III, or IV or a history of myocardial infarction, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, transient ischemic attack, cerebrovascular accident or decompensated congestive heart failure in the past 6 months. - Have poorly controlled hypertension at V1 or V2, malignant hypertension, renal artery stenosis, and/or evidence of labile blood pressure including symptomatic postural hypotension. Doses of antihypertensive medications must be stable for 30 days before randomization. -Have resting tachycardia at V1 or V2 or a history of a supraventricular tachycardia, ventricular tachycardia, or other cardiac arrhythmia that, in the opinion of the investigator, may preclude the patient from participating in the protocol. - Have an EKG considered by the investigator to be outside of normal limits and relevant for interpretation or indicating cardiac disease at V1. The following conduction abnormalities may confound QTc analysis and should be avoided: second- or third-degree atrioventricular block, delayed intraventricular conduction with QRS >120 msec, left bundle branch block, complete right bundle branch block, or Wolff-Parkinson-White. A QTc interval greater than450 msec in men and greater than 470 in women or a PR interval more than 220 msec are specifically excluded. - Personal or family history of long QT syndrome, family history of sudden death in a first-degree relative before age 40, or personal history of unexplained syncope within the last year. Use of prescription or over-the-counter medications known to prolong the QT or QTc interval. - Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or an alanine transaminase or aspartate aminotransferase levels >2.5 times the upper limit of the reference range at V1. - Have a serum creatinine >2 mg/dL or, in patients being treated with metformin, a serum creatinine above what is approved in the metformin product labeling in the respective country. - Have severe hypertriglyceridemia at V1. If taking lipid-lowering agents, doses of these medications must be stable for 30 days before randomization. - Evidence of hypothyroidism or hyperthyroidism based on clinical evaluation and/or an abnormal thyroid-stimulating hormone result at V1 and which, in the opinion of the investigator, would confound data interpretation or pose a risk to patient safety. Subjects
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to test the hypothesis that once-weekly injections of LY2428757 given to patients with T2DM inadequately controlled with diet and exercise alone, or metformin monotherapy, produces a significant decrease in the mean HbA1c from baseline to endpoint at 12 weeks as compared to placebo.;Secondary Objective: •Evaluate the safety and tolerability of LY2428757 given once-weekly for 12 weeks in patients with T2DM. •Evaluate and compare the percentage of patients requiring study discontinuation due to treatment failure for both LY2428757 and placebo. •Establish the dose response relationship for change in HbA1c in patients with T2DM given once-weekly LY2428757 with or without metformin. •Evaluate and compare the effects of LY2428757 and placebo on change in weight from baseline to endpoint. •Evaluate and compare the effects of LY2428757 and placebo on fasting and post-prandial plasma glucose levels and insulin secretory response. •Evaluate the population pharmacokinetics (popPK) and pharmacodynamics (PD) of LY2428757. •Evaluate the frequency and consequences of immune reactions to LY2428757. •Evaluate and compare the effects of LY2428757 and placebo on fasting lipid and lipoprotein values. For the rest of secondary objectives please refer to the protocol page 15.;Primary end point(s): The change in HbA1c, from baseline to endpoint, is the primary efficacy measure. Baseline is the Visit 3 HbA1c measurement. Endpoint will be the Visit 9 HbA1c measurement (12-week clinic visit). If a patient discontinues before study completion, then the last observed HbA1c measurement postrandomization will be used as endpoint. | — |
Countries
Austria, Germany, Spain, United Kingdom
Outcome results
None listed