Comparison of a Basal Plus One Insulin Regimen With a Biphasic Insulin Regimen in Type 2 Diabetes Patients

Study Overview
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Brief Summary
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The primary objective is to demonstrate the non-inferiority at six months of a basal plus one insulin regimen (Lantus plus one injection of Apidra) compared with a biphasic insulin regimen (NovoMix 30) at controlling glycosylated haemoglobin (HbA1c) in type 2 diabetes. The secondary objective are: To compare the proportion of patients in each treatment group reaching HbA1c target (< 7%) at the end of the treatment period To compare the rates of hypoglycaemia (total, severe, nocturnal) To compare the change in body weight from visit 10 to visit 24 To compare the change in diabetes specific quality of life and other patient reported outcomes from visit 10 to visit 24 Diabetes Treatment Satisfaction Questionnaire - status and change (DTSQs+c) Audit of Diabetes-Dependent Quality of Life (ADDQoL) questionnaire Insulin Treatment Satisfaction Questionnaire (ITSQ) EuroQoL 5 Dimensions (EQ5D) questionnaire To record the change in the daily dose of insulin from visit 2 to visit 10 and visit 10 to visit 24

Official Title
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Comparison of a Basal Plus One Insulin Regimen (Insulin Glargine/Insulin Glulisine) With a Biphasic Insulin Regimen (Insulin Aspart/Insulin Aspart Protamine 30/70) in Type 2 Diabetes Patients Following Basal Insulin Optimisation

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: INSULIN GLARGINE (HOE901)
* Drug: Insulin aspart
* Drug: Insulin Glulisine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Type 2 diabetes mellitus Patients being treated with Lantus once daily, Levemir once or twice daily or NPH insulin once or twice daily as a single insulin for at least three months 10.0% > or = HbA1c > or = 7.5% BMI < or = 40 kg/m² If patients are taking oral antidiabetics (OADs), the dose must be stable for at least 1 month Ability and willingness to perform blood glucose monitoring using a blood glucose meter and ability and willingness to use a patient diary Provision of written informed obtained prior to enrollment in the study Exclusion criteria: Type 1 diabetes mellitus Current or previous treatment with an insulin other than basal insulin (biphasic insulin, short acting insulin, rapid-acting insulin analogue) Treatment with GLP-1 receptor agonists or with DPPIV inhibitors in the 3 months before screening Active proliferative diabetic retinopathy, as defined by the application of photocoagulation or surgery, in the 6 months before screening or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgery during the study (confirmed by an optic fundus exam performed in the 2 years prior to screening) Unable or unwilling to enter either of the treatment arms Women who are pregnant or lactating (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method) History of hypersensitivity to the study drugs or to drugs with a similar chemical structure Treatment with systemic corticosteroids in the 3 months prior to study entry Treatment with any investigational product in the 2 months prior to study entry Current treatment with any non-selective beta-blockers Likelihood of requiring treatment during the study period with drugs not permitted by this clinical protocol Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major disease making implementation of the protocol or interpretation of the study results difficult Impaired hepatic function as shown by ALT and/or AST greater than three times the upper limit of normal at screening Impaired renal function as shown by serum creatinine >135 µmol/l in men and > 110 µmol/l in women at screening History of drug or alcohol abuse Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study Patient unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow-up visits, or unlikely to complete the study Patient is the investigator or any sub investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: Lantus + Apidra basal plus one<br>Before randomization (common with arm 2): A 1 to 2 weeks of screening period: patients will continue on their current insulin and oral antidiabetic drug (OAD) therapy. 8 weeks of run-in period: patients will switch their treatment for insulin glargine (one daily injection at bedtime) and all OADs (with the exception of metformin) will be discontinued. After randomization: 24 weeks of treatment period: Insulin (Lantus®) + metformin (if applicable) + a single injection of insulin glulisine (Apidra®), the latter administered at the patients largest meal of the day | Drug: INSULIN GLARGINE (HOE901)<br>* LANTUS®: Solution for injection. 100U/mL in a prefilled pen (SoloStar®)<br>Drug: Insulin Glulisine<br>* APIDRA®: Solution for injection. 100U/mL in a prefilled pen (SoloStar®)<br>|
| Active Comparator: NovoMix 30 Biphasic<br>Before randomization (common with arm 1): A 1 to 2 weeks of screening period: patients will continue on their current insulin and oral antidiabetic drug (OAD) therapy. 8 weeks of run-in period: patients will switch their treatment for insulin glargine (one daily injection at bedtime) and all OADs (with the exception of metformin) will be discontinued. After randomization: 24 weeks of treatment period: Insulin aspart/ insulin protamine crystallised insulin aspart (NovoMix® 30) + metformin (if applicable) | Drug: Insulin aspart<br>* NovoMix® 30: Suspension for injection. 100U/mL in a prefilled pen (FlexPen®)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycosylated Haemoglobin (HbA1c) |  | At week 7 and week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight |  | At week 8 and week 32 | 
| Diabetes specific quality of life measured using ADDQoL (Audit of Diabetes-Dependent Quality of Life questionnaire) and other patient reported outcomes measured using EQ5D (EuroQoL 5 Dimensions questionnaire) |  | Week 8 and week 32 | 
| Hypoglycaemia (total, severe and nocturnal) |  | At week 0 and week 32 |