Insulins Glargine and gluLisine strAtegy Versus Premixed Insulin strAteGy: a cOmparative Study (GALAPAGOS)

Sanofi

Status and phase: Completed; Phase 4

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: PREMIXED INSULIN; Drug: INSULIN GLARGINE; Drug: INSULIN GLULISINE

Study type: Interventional

Funder types: Industry

Identifiers

NCT01121835

LANTU_C_04589

U1111-1116-9859 (Other Identifier)

2009-018172-33 (EudraCT Number)

Details and patient eligibility

About

Primary Objective:

To demonstrate the superiority of a strategy with insulin glargine in comparison with a strategy including the premixed insulin in term of percentage of patients reaching HbA1c (glycosylated hemoglobin) below 7% at the end of treatment and who do not experience documented symptomatic hypoglycemia (confirmed by a Plasma Glucose (PG) below 56 mg/dL (3.1 mmol/L)) over a 24-week treatment period, in Type 2 diabetes patients failing lifestyle management and oral agents.

Secondary Objectives:

To assess the effect of insulin glargine in comparison with premixed insulin on :

• Evolution of HbA1c level during the treatment period Percentage of patients who reach the target of HbA1c < 7 % and who do not experience documented symptomatic hypoglycemia confirmed by a Plasma Glucose (PG) below 70 mg/dL (3.9 mmol/L)
• Percentage of patients who reach the target of HbA1c < 6.5% and who do not experience documented symptomatic hypoglycemia confirmed by a PG below 56 mg/dL (3.1 mmol/L) >Percentage of patients who reach the target of HbA1c < 6.5% and who do not experience documented symptomatic hypoglycemia confirmed by a PG below 70 mg/dL (3.9 mmol/L) >Evolution of Fasting Plasma Glucose Evolution of 7-point plasma glucose profiles
• Evolution of weight
• Hypoglycemia occurrence
• Dose of insulins
• Evolution of liver function
• Overall safety

Enrollment: 934 patients

Sex: All

Ages: 35+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 2 diabetes diagnosed for more than 1 year
• Insulin naïve
• Treated with lifestyle interventions and oral antidiabetic drugs, at least metformin at the maximum tolerated dose (with a minimum dose of 1g/day), for at least 3 months
• HbA1c ≥ 7.0 % and ≤ 10.5%
• Body mass index (BMI) ≤ 40 kg/m2
• Ability and willingness to perform plasma glucose (PG) monitoring using the sponsor-provided glucose meter and to complete the patient diary
• Willingness and ability to comply with the study protocol
• Signed informed consent obtained prior any study procedure

Exclusion criteria

• Treatment with glucagon-like peptide-1 (GLP-1) agonists in the 3 months prior to study entry
• Previous treatment with insulin (except for treatment of gestational diabetes or brief treatment with insulin for less than 1 week)
• Diabetes other than type 2 diabetes (e.g. type 1 diabetes, diabetes secondary to pancreatic disorders, drug or chemical agent intake)
• Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method)
• Hospitalized patient (except for routine diabetes check-up)
• Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by retina examination, in the 2 years prior to study entry
• History of sensitivity to the study drugs or to drugs with a similar chemical structure
• Impaired renal function: creatinine clearance < 60ml/min
• Impaired liver function (ALT, AST > 3 x upper limit of normal range)
• Severe gastro-intestinal disease
• Treatment with corticosteroids with potential systemic action within the 3 months prior to study entry
• Likelihood of requiring treatments during the study which are not permitted
• Treatment with an investigational product in the 30 days prior to study entry
• Alcohol or drug abuse within the last 5 years

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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934 participants in 2 patient groups

Insulin glargine

Experimental group

Description:

Administered once a day in the evening, at the same time every day. The starting daily dose is 0.2 U/Kg of body weight or 12 U, at the investigator's decision. Insulin glulisine is administered for patients of the insulin glargine group requiring insulin glulisine at week 12 (visit 11). Insulin glulisine is administered prior (10-15 min) to the main meal of the day, which is the meal with highest Post-Prandial Plasma Glucose (PPPG) on the 3 profiles performed before week 12. Starting dose is of 4 units per day.

Treatment:

Drug: INSULIN GLARGINE

Drug: INSULIN GLULISINE

Premixed insulin

Experimental group

Description:

administered once a day (in the evening at dinner) or twice a day (in the morning before breakfast and in the evening at dinner). Starting daily dose will be 6 U at breakfast and 6 U at dinner, if administered twice a day or 12 U at dinner if administered once a day

Treatment:

Drug: PREMIXED INSULIN