Type 2 Diabetes Mellitus MedDRA version: 17.1 Level: LLT Classification code 10049746 Term: Insulin-requiring type II diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Product Name: Insulin peglispro
Product Code: LY2605541
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Insulin peglispro
Other descriptive name: LY2605541
Concentration unit: U/ml un
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Have T2DM, based on the World Health Organization (WHO) classification, for =1 year. [2] Are 18-70 years of age, inclusive. [3] Use any type of basal insulin (except degludec), including once-or twice-daily human insulin NPH, insulin detemir, or insulin glargine. [4] Have HbA1c levels =9.0% according to central laboratory testing at Visit 1. [5] Have BMI =40.0 kg/m2. [6] Have been treated with stable doses of insulin for at least 30 days before Visit 1 with: • Basal insulin with daily doses ±30% of mean during the last 4 weeks. • Doses of a basal insulin must be between 0.3 U/kg/day and 1 unit/kg/day. [7] If on metformin, TZDs, SGLT-2 inhibitors, or DPP4 inhibitors, must be on stable doses for the last 30 days. [8] This inclusion criterion applies to all females of child-bearing potential: • Are not breastfeeding. • Test negative for pregnancy at Visits 1and 3 based on a serum pregnancy test. • Intend not to become pregnant during the study. • Have practiced reliable methods 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 before screening. • Agree to continue to use reliable methods of birth control as determined by the investigator during the study (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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: [14] Are using prandial, self-mixed, or premixed insulin. Patients using prandial insulin may be switched to daily glargine if investigator judges that the patient will still meet fasting glucose requirements for randomization. [15] Are using insulin pump therapy. [16] Have excessive insulin resistance: Defined as >1.0 U/kg/day as baseline treatment. [17] If being treated with SUs before Visit 1, then must have SUs washed out between Visit 1 and Visit 2. [18] Use any of these concomitant medications: morphine, codeine, antidiuretics, glucagon-like peptide-1 (GLP-1) receptor agonists (for example, exenatide, exenatide once weekly, lixisenatide or liraglutide), or pramlintide, used concurrently or within 90 days before Visit 1 (screening). [19] Have hypoglycemia unawareness, defined as confirmed by laboratory test results or by historical episodes of hypoglycemia 400 mg/dL (>4.5 mmol/L) at Visit 1, as determined by the local laboratory. [21] If currently taking prescription or over-the-counter medications to promote weight loss, should discontinue use of the medication at Visit 1. [22] Have had any episode of severe hypoglycemia (defined by requiring assistance due to neurologically disabling hypoglycemia) within 6 months before entry into the study. [23] Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months. [24] Have had a previous clinically significant episode of ketoacidosis as determined by the investigator (ketone bodies at fasting and without acidosis is acceptable) in the past 6 months. If the investigator is in doubt, C-peptide should be measured, and patients should be excluded if confirmed as Cpeptide negative (while having a fasting C-peptide in the normal range). [25] Have 1 of the following concomitant diseases: clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease or positive for human immunodeficiency virus (HIV), or have signs of active hepatitis B or C as determined by the investigator, for participation. [26] Have known history of cardiovascular disease (including angina, transient ischemic attack [TIA], significant arrhythmia, stroke, myocardial infarction [MI], or peripheral vascular disease), or history of coronary artery bypass graft (CABG) or percutaneous coronary interventions (such as coronary arterial stent insertion or coronary angioplasty). [27] Have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association Cardiac Disease Classification) (Attachment 7). [28] Have history of seizure disorder. [29] Have history of renal transplantation, are currently receiving renal dialysis, or have estimated Glomerular Filtration Rate (eGFR) <60 mL/min (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). [30] Have any known metabolic or lactic acidosis; have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis; or have had a radiologic contrast study within 48 hours before study entry. [31] Have obvious clinical signs or symptoms of liver disease (excluding nonalcoholic fatty liver disease), acute or chronic hepatitis, nonalcoholic steatohepatitis, or elevated liver enzyme measurements as indicated below: ? total bilirubin 2× the upper limit of normal (ULN) as defined by the local laboratory, or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that clinically significant hypoglycemia (defined as blood glucose <54 mg/dL (3.0 mmol/L) or symptoms of severe hypoglycemia) is significantly less frequent following a double dose of insulin peglispro than following a double dose of insulin glargine within 84 hours of double dosing in patients with T2DM.;Secondary Objective: 1. Evaluate the PK of insulin peglispro and insulin glargine after the double dose. 2. Compare measures of glycemic control for the 84 hours following double doses of insulin peglispro and insulin glargine, including: incidence of hypoglycemia, mean nadir glucose, time to mean nadir glucose, mean duration in minutes (per patient) with glucose =70 mg/dL (3.9mmol/L) and fasting blood glucose. 3. Compare measures of glycemic control following a standard dose of insulin peglispro and a double dose of insulin peglispro, including: incidence of hypoglycemic events fasting blood glucose. 4. Compare the effects during the day following the standard dose of insulin peglispro and insulin glargine on, including: glucose area under the concentration-time curve (AUC), Glucose AUC excursion and beta cell function ;Primary end point(s): Clinically significant hypoglycemia is significantly less frequent following a double dose of insulin peglispro that for insulin glargine;Timepoint(s) of evaluation of this end point: Within 84 hours of double dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Evaluation of PK of both insulin peglispro and insulin glargine - Incidence of hypoglycemia (blood glucose =70 mg/dL (3.9mmol/L)) - Incidence of clinically significant hypoglycemia (blood glucose =54 mg/dL (3.0mmol/L)) - Mean nadir glucose - Time to nadir glucose, which is =70 mg/dL (3.9mmol/L) - Mean duration in minutes (per patient) with glucose =70 mg/dL (3.9mmol/L) - Fasting blood glucose - Incidence of hypoglycemic events, defined as =70 mg/dL (3.9mmol/L) ;Timepoint(s) of evaluation of this end point: - 84 hours following double dose for all secondary objectives - within 12 and 84 hours from double dose (evaluate PK of insulin peglispro and insulin glargine, incidence of hypoglycemia) - within 12 hours from double dose (incidence of clinically significant hypoglycemia) - First, second and third days following the double dose (fasting blood glucose) - window between the first inpatient standard dose and the second inpatient standard dose versus the incidence on the first, second, and third days following the double dose (incidence of hypoglycemia events) - window between first inpatient standard dose and the second inpatient standard dose versus the first, second, and third days following the double dose (fasting blood glucose) | — |
Countries
Germany, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed