A Study Comparing Insulin Intensification Therapies in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of the study is to compare the effects on overall glycaemic control of two insulin intensification therapies.

Official Title
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A Comparison of Premixed and Basal-Bolus Insulin Intensification Therapies in Patients With Type 2 Diabetes Mellitus With Inadequate Glycaemic Control on Twice-daily Premixed Insulin

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Lispro Premix
* Drug: Insulin Glargine
* Drug: Insulin Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Present with type 2 diabetes mellitus Have been receiving twice-daily premixed insulin therapy with or without metformin and/or alpha-glucosidase inhibitors, for at least six months prior to study entry Have Haemoglobin A1c (HbA1c) >7.0% and <12.0% Exclusion Criteria: Within the last 3 months prior to entry into the study, are taking any non-permitted glucose-lowering agents, or are taking any non-permitted oral antihyperglycaemic medications Are pregnant or intend to become pregnant during the course of the study, or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable. Are women who are breastfeeding. Have an irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night). Do not regularly consume three meals per day. Have a body mass index >35 kilogram per square meter (kg/m^2). Have had more than one episode of severe hypoglycaemia within 24 weeks prior to entry into the study. Have cardiac disease with a functional status that is Class III or IV Have a history of renal or liver disease Have used less than or equal to 20 Units per day (U/day) of insulin during the past 90 days for more than 14 days (accumulated).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Premixed Insulin<br>Twice daily (before breakfast and lunch) insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension [LM50]) and once daily (before dinner) insulin lispro mix 25 (25% insulin lispro, 75% insulin lispro protamine suspension [LM25]) | Drug: Insulin Lispro Premix<br>* Participant dependent dose, administered subcutaneously for 24 weeks<br>* Other names: LY275585;|
| Active Comparator: Basal-Bolus<br>Once daily (bedtime) insulin glargine and three pre-meal insulin lispro | Drug: Insulin Glargine<br>* Participant dependent dose, administered subcutaneously for 24 weeks<br>Drug: Insulin Lispro<br>* Participant dependent dose, administered subcutaneously for 24 weeks<br>* Other names: LY275585;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Haemoglobin A1c (HbA1c) From Baseline to 24 Week Endpoint | Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) with the change from baseline in HbA1c at all post baseline measurement as dependent variables, treatment, country, visit and treatment by visit interaction as fixed effects, baseline HbA1c value as a covariate and participant as a random effect. | Baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to 12 Week Endpoint | Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) with the change from baseline in HbA1c at all post baseline measurement as dependent variables, treatment, country, visit and treatment by visit interaction as fixed effects, baseline HbA1c value as a covariate and participant as a random effect. | Baseline, 12 weeks | 
| The Percentage of Participants Who Achieved Haemoglobin A1c (HbA1c) Less Than or Equal to 6.5% and Less Than or Equal to 7% at 12 Weeks and 24 Weeks | The Percentage of participants achieving a haemoglobin A1c (HbA1c) less than or equal (<=) to 6.5% or 7% is defined as 100 multiplied by the number of participants with a HbA1c of the cut-off value (6% or 7%) divided by the number of participants exposed to study drug. Participants with missing HbA1c values at endpoint were treated as not achieving the HbA1c goal. | 12 weeks, 24 weeks | 
| The 7-point Self-monitored Blood Glucose (SMBG) Profiles at Baseline, 12 Weeks and 24 Weeks. | 7-point Self-monitored Blood Glucose (SMBG) Profiles are measures of blood glucose taken 7 times a day at the morning pre-meal, morning 2-hours post-meal, midday pre-meal, midday 2-hours post-meal, evening pre-meal, evening 2-hours post-meal, and 0300 hour [3 am]. Each participant took measures on 3 non-consecutive days and the average was calculated for each of the 7 time points. The mean of the 7-point averages was calculated for all the participants at baseline, Weeks 12 and 24. | Baseline, 12 weeks, and 24 weeks | 
| Daily Dose of Insulin: Total, Basal, and Prandial |  | 24 weeks | 
| Change in Body Mass Index (BMI) From Baseline to 12 and 24 Weeks | Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) using change from baseline in BMI at all post baseline measurement as dependent variables, treatment, country, visit and treatment by visit interaction as fixed effects, baseline BMI value as a covariate and participants as a random effect. | Baseline, 12 weeks, and 24 weeks | 
| Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial |  | 24 weeks | 
| Percentage of Participants With Hypoglycemic Episodes (Incidence) | Incidence of hypoglycemic episodes is defined as 100 multiplied by the number of participants experiencing a hypoglycemic episode divided by the number of participants exposed to study drug. Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L). | baseline through 24 weeks | 
| The Rate of Hypoglycemic Episodes | The rate of hypoglycemic episodes is defined as the mean number of hypoglycemic episodes per 30 days per participant. Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L). | baseline through 24 weeks | 
| Percentage of Participants Experiencing a Severe Hypoglycemic Episode | Severe hypoglycemic episode is defined as any event requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. The percentage of participants experiencing a severe hypoglycemic episode is defined as the 100 multiplied by the number of participants experiencing a severe hypoglycemic episode divided by the number of participants exposed to study drug. | baseline through 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic Diseases, Diabetes Mellitus, Type 2, Glargine, Diabetes Mellitus, Insulin LISPRO, Insulin