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
Interventions
Product Code: LY2605541
Pharmaceutical Form: Solution for injection in pre-filled pen
Current Sponsor code: LY2605541
Other descriptive name: LY2605541
Concentration unit: U/ml unit(s)/millilitre
Conc
Sponsors
Lilly S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Have T2DM (per World Health Organization [WHO] Classification of Diabetes) [2] Are 18 years of age or older [3] Have had diabetes for at least 1 year [4] Have been receiving basal insulin (NPH [isophane], insulin detemir or insulin glargine) and from 0 to 3 OAMs for at least 90 days prior to the study. Doses of any OAMs are required to have been stable for ?90 days prior to screening and at least 1 of the OAMs must be dosed at, or above, half the maximum daily dose allowed by local regulations or at the maximally tolerated dose. ? Note: OAMs must be used in accordance with the corresponding product label at the time of screening. Combination treatments of the OAMs are acceptable if they meet the above criteria. Combination medications should be counted as the number of individual components. [5] Have HbA1c ?9.0% according to central lab at screening [6] Have BMI ?45.0 kg/m2 [7] Are capable of, and willing to do, the following, as determined by the investigator: ? Inject insulin with a prefilled pen and perform self blood glucose monitoring, and ? Record keeping as required by this protocol. Caregiver may be responsible for all of the above. [8] This inclusion criterion applies to females of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) only: ? Are not breastfeeding; ? Test negative for pregnancy at the time of screening and randomization based on a serum 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 307 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 119
Exclusion criteria
Exclusion criteria: [12] Insulin therapy: have used a routine regimen of insulin glargine twice daily in the past 90 days or have used routine, prandial (rapid-acting) insulin therapy (outside of pregnancy) anytime in the past 6 months, except for short-term treatment of acute conditions, and up to a maximum of 4 continuous weeks. Insulin use of any type or 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 90 days prior to screening. [14] Local OAM restrictions: for patients on OAMs, restrictions for cardiac, renal, and hepatic diseases in the local product regulations must apply. [15] Weight loss medications: are currently taking, or have taken within the 90 days preceding screening, 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 screening. [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] Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association [NYHA] Cardiac Disease Classification) [19] Renal: have a history of renal transplantation, or are currently receiving renal dialysis or have serum creatinine ?2 mg/dL (177 ?mol/L). [20] Hepatic: 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] Hematologic: have had a blood transfusion or severe blood loss within 3 months prior to screening 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] Malignancy: 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 are at increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator. [23] Allergy: have known hypersensitivity or allergy to any of the study insulins or their excipients. [24] Glucocorticoid therapy: 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 screening. [25] Triglycerides: have fasting triglycerides >400 mg/dL (>4.5 mmol/L) at screening as determined by the central laboratory. [26] Sleep cycle: have irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night) in the investigator?s opinion. [27] Adherence to protocol: have any othe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate that LY2605541 is noninferior to insulin glargine for the change in HbA1c from baseline to 26 weeks of treatment in patients with T2DM treated with basal insulin alone or in combination with oral antihyperglycemic medication(s) (OAMs);Secondary Objective: The secondary gated objectives are to demonstrate that LY2605541 is superior to insulin glargine (at 26 weeks) for: 1. Nocturnal hypoglycemia rate 2. Proportion of patients with HbA1c <7.0% and no nocturnal hypoglycemia 3. HbA1c change from baseline 4. Proportion of patients with HbA1c <7.0% 5. Total hypoglycemia rate 6. Fasting serum glucose (FSG) by laboratory The secondary non-gated objectives are to compare the efficacy and safety of LY2605541 vs insulin glargine for the following objectives: ? All of the above at other timepoints AND ? Total and nocturnal hypoglycemic incidences ? FBG (by self-monitored blood glucose [SMBG]) ? FBG intra-patient variability by SMBG ? Weight change from baseline ? 6-point SMBG profile ? Proportion of patients with HbA1c ?6.5% ? HbA1c ? Insulin dose ? Number of dose adjustments to steady-state ? Triglycerides, total cholesterol, LDL C, HDL-C;Primary end point(s): Change in HbA1c from baseline;Timepoint(s) of evaluation of this end point: 26 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Total and nocturnal hypoglycemia rate; proportion of patients with at least 1 hypoglycemia event for each hypoglycemia category; proportion of patients with HbA1c ?6.5% and <7.0%; proportion of patients with HbA1c <7.0% without nocturnal hypoglycemia; FSG (laboratory measurements); FBG (by SMBG); FBG intra patient variability (SMBG), as measured by standard deviation; SMBG 6-point profile; weight change from baseline; HbA1c actual and change from baseline; insulin dose; number of dose adjustments to steady-state;Timepoint(s) of evaluation of this end point: - 26 weeks: all gated objective endpoints - 0 to 12 weeks, 12 to 26 weeks, 0 to 26 weeks, 26 to 52 weeks, 0 to 52 weeks, and by visit: total and nocturnal hypoglycemia rate and proportion of patients with at least 1 hypoglycemia event for each hypoglycemia category - 26 and 52 weeks: proportion of patients with HbA1c ?6.5% and <7.0%; proportion of patients with HbA1c <7.0% without nocturnal hypoglycemia - By visit: FSG (laboratory measurements); FBG (by SMBG); FBG intra patient variability (SMBG), as measured by standard deviation; SMBG 6-point profile; weight change from baseline; HbA1c actual and change from baseline; insulin dose - number of dose adjustments to steady-state | — |
Countries
Czech Republic, Germany, Greece, Israel, Romania, Russian Federation, Spain, United States
Contacts
Public ContactClinical Trial Information
Eli Lilly
Outcome results
None listed