The Impact of LY2189265 versus Insulin Glargine Both in Combination with Insulin Lispro for the Treatment to Target of Type 2 Diabetes Mellitus(AWARD-4: Assessment of Weekly AdministRation of LY2189265 in Diabetes – 4) - GBDD(a)

Phase 1

• Conditions: Type 2 Diabetes Mellitus; MedDRA version: 14.0Level: PTClassification code 10012601Term: Diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders

• Registration Number: EUCTR2010-019223-55-BE
• Lead Sponsor: Eli Lilly & Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09-21
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 837

Inclusion Criteria

[1] - Are patients with type 2 diabetes mellitus (based on the World Health Organization’s [WHO] diagnostic criteria, Protocol Attachment 3) with a screening (Visit 1) HbA1c level = 7.0% and =11% after being treated for at least 3 months with a conventional insulin regimen with or without OAMs:
•Conventional insulin regimen is defined as 2 or less doses of insulin per day including any combination of basal, basal with prandial, or premixed insulin (excluding any prandial only regimen).
•If the most commonly administered total daily dose is ?40 units, then all total daily doses during the prior 3 months should be within ±10% of the most commonly administered total dose to confirm that intensification of therapy is needed.
•If the most commonly administered total daily dose is <40 units, then all total daily doses during the prior 3 months should be within ±4 units of that most commonly administered total daily insulin dose.
[2]- Are at least 18 years of age.
[3]- Are men or nonpregnant women.
Women of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) must:
[a]- test negative for pregnancy at Visit 1, based on a serum pregnancy test;
[b]- agree to use a reliable method of birth control (for example, oral contraceptives or Norplant®; a reliable barrier method of birth control [diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, intrauterine devices]; or have a partner with vasectomy; or maintain abstinence) during the study and for 1 month following the last dose of study drug; and
[c]- not be breastfeeding.
[4]- Are of stable weight (±5%) =3 months prior to screening.
[5]- Have a body mass index (BMI) between 23 and 45 kg/m2, inclusive.
[6]- In the investigator’s opinion, are well motivated, capable, and willing to:
[a]- inject LY2189265 once weekly or insulin glargine once daily in addition to injecting insulin lispro 3 times a day, prior to meals (patients who are visually impaired or have physical limitations and are unable to perform the injections must have the assistance of an individual trained to inject study drugs);
[b]- self-monitor blood glucose to adjust insulin dose(s) to achieve glycemic targets; and
[c]- maintain a study diary, as required for this protocol.
[7]- Inclusion criterion [7] has been deleted.
[8]- 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

[9]- Are patients with type 1 diabetes mellitus.
[10]- Have received therapy with any GLP-1 receptor agonists (for example, exenatide or liraglutide) within the 3 months prior to Visit 1.
[11]- Have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma requiring hospitalization within the 6 months prior to Visit 1.
[12]- Have been treated with prescription or over-the-counter medications that promote weight loss within 3 months of Visit 1.
[13]- Are receiving chronic (>2 weeks or 14 days) systemic glucocorticoid therapy (excluding topical, intra-ocular, intranasal, or inhaled preparations) or have received such therapy within 1 month of Visit 1.
[14]- Have any of the following CV conditions within 2 months prior to Visit 1: acute myocardial infarction, New York Heart Association (NYHA) class III or class IV heart failure, or cerebrovascular accident (stroke).
[15]- Have a known clinically significant gastric emptying abnormality (for example, severe diabetic gastroparesis or gastric outlet obstruction), have undergone gastric bypass (bariatric) surgery, or chronically take drugs that directly affect gastrointestinal (GI) motility.
[16]- Have acute or chronic hepatitis, signs or symptoms of any other liver disease, or an alanine transaminase (ALT) level >3.0 the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Patients with nonalcoholic fatty liver disease are eligible to participate.
[17]- Have signs and symptoms of chronic pancreatitis, acute idiopathic pancreatitis, or have been diagnosed with any form of pancreatitis.
[18]- Estimated glomerular filtration rate (eGFR) =30 mL/min/1.73 m2 at screening.
[19]- Have evidence of a significant, uncontrolled endocrine abnormality (for example, thyrotoxicosis or adrenal crises), in the opinion of the investigator.
[20]- Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in absence of known medullary C-cell lesions. The only exception to this exclusion will be for patients in whom genetic testing has been previously performed and is known to be NEGATIVE for the mutation that exists in affected family members. If genetic testing has not been done, or is POSITIVE or unknown, then the exclusion applies.
[21]- Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, or carcinoma (including sporadic, familial or part of MEN 2A or 2B syndrome).
[22]- Have a serum calcitonin level of =20 pg/mL at Visit 1.
[23]- Have evidence of a significant, active autoimmune abnormality (for example, lupus or rheumatoid arthritis).
[24]- Have any other condition not listed in this section (for example, hypersensitivity) that is a contraindication to LY2189265, insulin glargine, or insulin lispro.
[25]- Have had a transplanted organ (corneal transplants [keratoplasty] allowed).
[26]- Have a history of an active or untreated malignancy, or are 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.
[27]- Have a history of any other condition (such as known drug or alcohol abuse or psychiatric disorder) that, in the opinion of the investigator, may preclude the patient from following and completing the protocol.
[28]- Have any hematological condition that may interfere with HbA1c measurement (for example, hemolytic anemias, sickl

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the effect of once-weekly 1.5 mg LY2189265, to that of insulin glargine (treated-to-target) on HbA1c at 26 weeks (change from baseline) in patients with type 2 diabetes who are treated in combination with prandial insulin lispro, using a non-inferiority analysis.;Secondary Objective: The following key secondary objectives will compare glycemic control (change from baseline) between LY2189265 (1.5 mg and 0.75 mg) and insulin glargine:<br>• To demonstrate that 0.75 mg LY2189265 is noninferior to insulin glargine<br>at 26 weeks.<br>• To demonstrate that 1.5 mg LY2189265 is superior to insulin glargine at<br>26 weeks.<br>• To demonstrate that 0.75 mg LY2189265 is superior to insulin glargine at<br>26 weeks.<br><br>See protocol for additional secondary objectives.;Primary end point(s): The primary efficacy measurement in this study is HbA1c change from baseline at<br>26 weeks.