Lispro Mid Mixture (MM) Intensive Mixture Therapy With Progressive Dose-Titration of Lispro Low Mixture (LM) or Biphasic Insulin Aspart 30/70 (S019)

Study Overview
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Brief Summary
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Investigation into patients with type 2 diabetes mellitus not achieving adequate glycemic control while treated with combination of premixed insulin analogue formulations twice daily and metformin will be randomly assigned to follow one of two insulin treatment strategies used in combination with metformin administration. The aim of the trial is to try to achieve optimal metabolic control and explore full therapeutic potential of the strategies, patients in both arms will follow progressive insulin dose titration algorithms for 16 weeks.

Official Title
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A Comparison of Insulin Lispro MM Intensive Mixture Therapy With Progressive Dose-Titration of Insulin Lispro LM or Biphasic Insulin Aspart 30/70

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Biphasic Aspart 30/70
* Drug: insulin lispro LM
* Drug: insulin lispro MM
* Drug: insulin lispro LM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have type 2 diabetes (World Health Organization [WHO] classification). Are at least 30 years of age and less than 75 years of age. Have been receiving hypoglycemic treatment with premixed insulin analogue (either with insulin lispro LM or biphasic insulin aspart 30/70) administered twice daily in combination with at least 1500 milligrams (mg) of metformin per day for at least 60 days immediately prior to the study. Have a hemoglobin A1c 1.2 to 1.8 times the upper limit of the normal reference range at the local laboratory at Visit 1 or Have at least 6 of 9 of the postprandial blood glucose values recorded in the period between Visit 1 and Visit 2 exceeding 180 milligrams per 100 milliliters (mg/dl) (10.0 millimole per liter [mmol/l]). Have given written informed consent to participate in this study in accordance with local regulations. Exclusion Criteria: Are taking any other oral anti-diabetic medication (OAM) not mentioned in inclusion criterion. Have a body mass index greater than 40 kilograms per meter squared (kg/m2). Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study. Have congestive heart failure. Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night).

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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: insulin lispro LM + insulin lispro MM<br>Three times per day subcutaneous injection of insulin lispro mid mixture (MM) with the possibility to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved. | Drug: insulin lispro LM<br>* Participant adjusted dose, injected subcutaneously for 16 weeks - possibility of using instead of insulin lispro MM before evening meal if there is a risk of hypoglycemia after the dinner or high fasting glucose levels.<br>* Other names: Humalog;Drug: insulin lispro MM<br>* Participant adjusted dose, three times per day, injected subcutaneously for 16 weeks<br>* Other names: Humalog;|
| Active Comparator: Insulin Biphasic Aspart 30/70 or Insulin Lispro LM<br>Twice daily subcutaneous injection of either insulin biphasic aspart 30/70 or insulin lispro low mixture (LM) (continuation of analogue formulation used before study enrollment). | Drug: Insulin Biphasic Aspart 30/70<br>* Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks<br>Drug: insulin lispro LM<br>* Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks<br>* Other names: Humalog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c (HbA1c) at 16 Week Endpoint |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving Hemoglobin A1c (HbA1c) <7% and HbA1c ≤6.5% at 16 Week Endpoint |  | 16 weeks | 
| Change From Baseline in Hemoglobin A1c (HbA1c) at 16 Week Endpoint |  | Baseline, 16 Weeks | 
| 2-hour Postprandial Plasma Glucose Concentrations After the Midday Meal From Self-monitored 7-point Plasma Glucose at 16 Week Endpoint | Participants self-monitored their blood glucose concentrations at 7 time points: three premeal and three 2-hour postprandial meal measurements for the morning (breakfast), midday (lunch), and evening (dinner) meals, as well as a 3:00 AM measurement. Results presented here are for the blood glucose concentrations 2-hours after the midday meal at Week 16. | 16 weeks | 
| Mean 2-hour Postprandial Blood Glucose Excursions After Midday Meal at 16 Week Endpoint | Participants self-monitored their blood glucose concentrations at 7 time points: three premeal and three 2-hour postprandial meal measurements for the morning (breakfast), midday (lunch), and evening (dinner) meals, as well as a 3:00 AM measurement. Results presented here are for the difference (excursion) between midday premeal and 2-hour postprandial midday meal blood glucose concentrations at Week 16. | 16 weeks | 
| Mean Daily Blood Glucose Values at 16 Week Endpoint |  | 16 weeks | 
| Number of Patients With Self-reported Hypoglycemic Episodes | Hypoglycemia: any time a patient feels, or another person observes, that patient is experiencing a sign/symptom that he or she would associate with hypoglycemia or a plasma-equivalent glucose measurement ≤70 mg/dL. Nocturnal hypoglycemia: hypoglycemia occurring after bedtime and prior to morning meal and morning dose of insulin or metformin. Severe hypoglycemia: hypoglycemia where patient requires assistance from another person and which is associated with either a blood glucose level less than 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration. | Baseline through 16 weeks | 
| 30-Day Adjusted Rate of Hypoglycemic Events | Hypoglycemia: any time a patient feels, or another person observes, that patient is experiencing a sign/symptom that he or she would associate with hypoglycemia or a plasma-equivalent glucose measurement ≤70 mg/dL. Nocturnal hypoglycemia: hypoglycemia occurring after bedtime and prior to morning meal and morning dose of insulin or metformin. Severe hypoglycemia: hypoglycemia where patient requires assistance from another person and which is associated with either a blood glucose level less than 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration. | Baseline through 16 weeks | 
| Change From Baseline in Weight at 16 Week Endpoint |  | Baseline, 16 weeks | 
| Total Daily Insulin Dose at 4 Weeks and 12 Weeks |  | 4 weeks and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, type 2