Evaluation of Insulin Glargine in Combination With Sitagliptin in Type 2 Diabetes Patients: EASIE Extension Trial

Study Overview
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Brief Summary
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This study was the extension of the LANTU_C_02761 study named EASIE and identified as NCT00751114 (core study comparing insulin glargine versus sitagliptin in insulin-naïve patients treated with metformin and not adequately controlled). All patients with Glycosylated Hemoglobin A1c (HbA1c) ≥ 7% at the end of the core study had the possibility to enter this extension study if they met the other inclusion criteria and did not present with any exclusion criteria. The visit 14 of the core study (week 24) was the visit 1 (baseline, week 0) of the extension study which consisted of a 12-week treatment period. The objectives of this extension study were: To assess the glycemic control (HbA1c <7%) of a 3-month combination therapy with metformin, insulin glargine and sitagliptin in patients not adequately controlled by a previous treatment with metformin plus either insulin glargine or sitagliptin. To assess the effect of insulin glargine in combination with sitagliptin on HbA1c level, fasting plasma glucose, 7-point glucose profile, hypoglycemia occurrence, body weight and overall safety.

Official Title
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Combination Therapy of Insulin Glargine and Sitagliptin in Patients With Type 2 Diabetes Not Adequately Controlled by a Previous Treatment With Metformin and Either Insulin Glargine or Sitagliptin

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Glargine
* Drug: Sitagliptin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients who completed the core study LANTU_C_02761 (NCT00751114) i.e. went through the visit 14 investigation, HbA1c >= 7 %, Dose of metformin compliant with the inclusion criteria of the core study (i.e. at least 1 g/day), and maintained stable for the duration of the core study Ability and willingness to perform plasma blood glucose monitoring using the sponsor-provided plasma glucose meter and to complete the patient dairy, Signed informed consent obtained prior any study procedure, Willingness and ability to comply with the study protocol. Exclusion Criteria: Treatment with oral antidiabetic drugs other than metformin and sitagliptin in the core study, Treatment with insulin other than Insulin Glargine in the core study (except in case of an emergency, for a period of time less than 7 days), Treatment with a non-permitted drug during the core study, Pregnant or lactating women, In-patient care, Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study (an optic fundus examination should have been performed within the 2 years prior to study entry in the core study), Impaired renal function: serum creatinine >= 1.5 mg/dL (>= 133µmol/L) or >= 1.4 mg/dL (>=124 µmol/L) in men and women, respectively, History of sensitivity to the study drugs or to drugs with a similar chemical structure, Impaired hepatic function: alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 3 x upper limit of normal range, Alcohol or drug abuse within the last year, Night shift worker, Presence of any condition (medical, psychological, social or geographical), current or anticipated that the investigator feels would compromise the patient's safety or limit the patient successful participation in the study, Treatment with weight loss medications (e.g. sibutramine, orlistat, rimonabant), History of pancreatitis.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 71 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination insulin glargine and sitagliptin<br>Insulin glargine administered once a day, in the evening, at dinner or at bedtime. Starting dose: - last dose administered in the core study for patients previously treated with insulin glargine, - 0.2 U/Kg of body weight for patients previously treated with sitagliptin. Monitoring of blood glucose and titration: all patients, irrespective of their previous treatment group in the core study were empowered to adjust their insulin doses, under strict investigator's supervision. The goal was to achieve through a force titration 70 < Fasting Plasma Glucose (FPG) ≤ 100 mg/dL (3.9 <FPG ≤ 5.5 mmol/L). Sitagliptin: stable dose of 100 mg once a day administered with or without food. | Drug: Insulin Glargine<br>* Subcutaneous injection. 100 Units/mL solution for injection in a prefilled SoloStar® pen (3 mL).<br>* Other names: Lantus®;Drug: Sitagliptin<br>* Oral administration. 100mg film-coated tablets.<br>* Other names: Januvia®;Drug: Metformin<br>* Patients continued with metformin as usual oral anti-diabetic treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Response Rate: Percentage of Patients Achieving Glycosylated Haemoglobin A1c (HbA1c) < 7% at Study Endpoint (End of Treatment Period) |  | study endpoint: week 12 or earlier in case of premature discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c: Change From Baseline to Study Endpoint | Change = study endpoint - baseline | baseline, study endpoint: week 12 or earlier in case of premature discontinuation | 
| Self-Monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpoint | SMFPG mean = mean of the fasting plasma glucose values recorded on the 6 consecutive days before the visit (at least 3 values needed). Change = study endpoint - baseline. | baseline, study endpoint: week 12 or week 8 if value not available at week 12 | 
| 7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint | 7-point plasma glucose recorded before and after breakfast, before and after lunch, before and after dinner and at bedtime. Change = study endpoint - baseline. | baseline, study endpoint: week 12 or week 8 if value not available at week 12 | 
| Insulin Dose | Daily dose at the face-to-face visits | baseline, week 4, week 8, week 12 | 
| Number of Patients With at Least One Episode of Symptomatic Hypoglycemia | Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia confirmed or not by a plasma glucose measurement <= 70mg/dL [3.9 mmol/L] | During the treatment period (12 weeks) plus 7 days after last dose | 
| Change in Body Weight From Baseline to Study Endpoint | Change = study endpoint - baseline | baseline, study endpoint: week 12 or week 8 or week 4 depending on last available value |