| 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 | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10012601 |
| E.1.2 | Term | Diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| 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 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. |
|
| E.2.2 | Secondary objectives of the trial |
The following key secondary objectives will compare glycemic control (change from baseline) between LY2189265 (1.5 mg and 0.75 mg) and insulin glargine:
• To demonstrate that 0.75 mg LY2189265 is noninferior to insulin glargine
at 26 weeks.
• To demonstrate that 1.5 mg LY2189265 is superior to insulin glargine at
26 weeks.
• To demonstrate that 0.75 mg LY2189265 is superior to insulin glargine at
26 weeks.
See protocol for additional secondary objectives. |
|
| 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 |
Continuous Glucose Monitoring:
The purpose of this sub-study is to evaluate the 24-hour glucose profile for LY2189265 versus insulin glargine when either is used in combination with insulin lispro prior to meals.
The objective is to compare the 2 therapeutic interventions for percentage of time in the optimum target range for blood glucose control, to determine the percentage of time in the hyper- and hypoglycemia range, and to evaluate the glucose variability in response to therapy.
The sub-study will be offered to a subgroup of patients at selected sites, but not in Belgium. |
|
| E.3 | Principal 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.
|
|
| E.4 | Principal 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, sickle-cell disease).
[29]- 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.
[30]- Are Lilly employees.
[31]- Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device (other than the study drug/device used in this study), or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
[32]- Have previously completed or withdrawn from this study or any clinical trial of LY2189265 after providing informed consent.
[33]- Are patients who are currently treated with three or more doses of insulin daily (MDI regimen ).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy measurement in this study is HbA1c change from baseline at
26 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 | 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 | Yes |
| 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 | 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| 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
|
| Last Visit of Last Subject |
|
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
