Type 2 Diabetes Mellitus MedDRA version: 14.1 Level: LLT Classification code 10049746 Term: Insulin-requiring type II diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] T2DM (per World Health Organization [WHO] Classification of Diabetes not treated with insulin [2] Age 18 years of age or older [3] Duration of diabetes = 1 year [4] Have been receiving at least 2 oral anti-hyperglycemic medications (OAMs) for at least 3 months prior to the study. Two or more medications may be contained in one pill. Doses of any OAMs are required to have been stable for the 3 months prior to screening and at least 2 of the OAMs must be dosed at or above half the maximum daily dose allowed by local regulations or the maximally tolerated dose of OAM. • Note: OAMs must be used in accordance with the corresponding product label. Combination treatments of the OAMs are acceptable if they meet the above criteria. Combination medications should be counted as the number of individual components. • For Metformin: Where the maximally allowed daily dose of metformin is 2g or greater the metformin (any formulation) must be dosed daily at 1g or greater or at the maximally tolarated dose. [5] HbA1c of 7.0% to 11.0%, inclusive, according to central lab at screening [6] BMI = 45 kg/m2 [7] Capable of, and willing to do the following: • Inject insulin with a vial and syringe and perform self blood glucose monitoring, and • Record keeping as required by this protocol, as determined by the investigator Caregiver may do all of the above. [8] Have given written informed consent to participate in this study in accordance with local regulations [9] Have access to a telephone [10] Have refrigeration in the home [11] This inclusion criterion applies to females of child-bearing potential (not surgically sterilized and between menarche and 1-year postmenopause) only. • Are not breastfeeding. • Test negative for pregnancy at the time of screening based on a urine pregnancy test. • Intend not to become pregnant during the study. • Have practiced a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) for at least 6 weeks prior to screening. • Agree to continue to use a reliable method of birth control during the study, as determined by the investigator (and for 2 weeks following the last dose of study drug). 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 1137 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 379
Exclusion criteria
Exclusion criteria: [12] Insulin therapy: have used insulin therapy (outside of pregnancy) anytime in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 continuous weeks. Insulin use of any duration during pregnancy is not considered an exclusion criterion. [13] Concomitant medications: rosiglitazone, pramlintide, glucagon-like peptide 1 (GLP-1) receptor agonist (for example, exenatide, exenatide once weekly, or liraglutide) used concurrently or within 3 months prior to Visit 1 (screening). [14] Local OAM restrictions: for patients on OAMs, restrictions for cardiac, renal, and hepatic diseases, local product regulations must apply. [15] Weight loss medications: are currently taking, or have taken within the 3 months preceding Visit 1, prescription or over-the-counter medications to promote weight loss. [16] Severe hypoglycemia history: have had any episodes of severe hypoglycemia within 6 months prior to Visit 1. [17] Diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar nonketotic coma (HHNKC): have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma in the past 6 months. [18] Have cardiac disease with functional status that is New York Heart Association Class III or IV [19] Have a history of renal transplantation, or are currently receiving renal dialysis or have serum creatinine =2 mg/dL (177 ?mol/L). [20] Have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease [NAFLD]), acute or chronic hepatitis, non alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements as indicated below: • total bilirubin =2 x the upper limit of normal (ULN) as defined by the central laboratory, or • alanine aminotransferase (ALT)/(serum glutamic pyruvic transaminase (SGPT) >2.5 x ULN as defined by the central laboratory, or • aspartate aminotransferase (AST)/(serum glutamic oxaloacetic transaminase (SGOT) >2.5 x ULN as defined by the central laboratory. [21] Have had a blood transfusion or severe blood loss within 3 months prior to Visit 1 or have known hemoglobinopathy, hemolytic anemia or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the measurement of HbA1c. [22] Have have active or untreated malignancy, have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years, or at increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator. [23] Have known hypersensitivity or allergy to any of the study insulins or their excipients. [24] Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intranasal, intraocular, and inhaled preparations) or have received such therapy within the 8 weeks immediately preceding Visit 1. [25] Have fasting triglycerides >400 mg/dL (>4.5 mmol/L) at Visit 1 as determined by the central laboratory. [26] Have irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night) in the investigator's opinion. [27] Have any other conditions (including known drug or alcohol abuse or psychiatric disorder) that preclude the patient from following and completing the protocol. [28] Are Lilly employees or Lilly representatives (including employees, temporary contract workers, or designees responsible for the conduct of the study) or Boehrin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate that LY2605541 is noninferior to insulin glargine for the change in HbA1c from baseline to 52 weeks of treatment in insulin naive patients with T2DM;Secondary Objective: Gated: 1. Nocturnal hypoglycemia rate during the first 52 weeks of treatment 2. Proportion of patients with HbA1c <7.0% at 52 weeks and no nocturnal hypoglycemia during the first 52 weeks of treatment 3. HbA1c change from baseline after 52 weeks of treatment 4. Proportion of patients with HbA1c <7.0% after 52 weeks of treatment 5. Total hypoglycemia rate during the first 52 weeks of treatment 6. Fasting serum glucose (FSG) by laboratory measurement after 52 weeks of treatment Non-Gated: 1. Total and nocturnal hypoglycemia rates 2. Total and nocturnal hypoglycemic incidences 3. Weight change from baseline 4. 6-point SMBG profile 5. Proportion of patients with HbA1c <7.0% at 26 and 78 weeks 6. Proportion of patients with HbA1c <7.0% and no nocturnal hypoglycemia at 26 and 78 weeks 7. Triglycerides), total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) 8. Antibodies to LY2605541;Primary end point(s): A change of HbA1c from baseline to 52 weeks that is not inferior to glargine.;Timepoint(s) of evaluation of this end point: 52 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Nocturnal and total hypoglycemia rates and incidences superior to glargine, proportion of patients with HbA1c <7% at 52 weeks of treatment (also HbA1c <7% with no nocturnal hypoglycemia, FPG by laboratory, FBG by SMBG, weight change from baseline, SMBG 6-pt profile, HbA1c, insulin dose, number of dose adjustments to steady state, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, insulin and insulin analog antibodies, other safety endpoints such as serious adverse events, vitals, treatment-emergent adverse events, Health Outcomes measurements EQ-5D, ITSQ, and LBSS.;Timepoint(s) of evaluation of this end point: All gated objective endpoints are at 52 weeks of treatment. Many of the non-gated secondary endpoints have various timepoints such as 0 to 12 weeks, 0 to 26 weeks, 0 to 78 weeks, 12 to 26 weeks, 26 to 52 weeks, 52 to 78 weeks for nocturnal and total hypoglycemia incidences; 0 to 12 weeks, 0 to 26 weeks, 0 to 52 weeks, 0 to 78 weeks, 12 to 26 weeks, 26 to 52 weeks, 52 to 78 weeks for nocturnal and total hypoglycemia rates; 26 and 78 weeks for FPG by laboratory, 26 and 78 weeks for proportion of patients with HbA1c <7%, and the same as immediately above with no nocturnal hypoglycemia, and HbA1c change from baseline | — |
Countries
Argentina, Australia, Brazil, Canada, Czech Republic, Finland, Germany, Greece, Hungary, Israel, Italy, Lithuania, Mexico, New Zealand, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Eli Lilly
Outcome results
None listed