Insulins Glargine and gluLisine strAtegy Versus Premixed Insulin strAteGy: a cOmparative Study - Full Text View

Purpose

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

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: INSULIN GLARGINE Drug: INSULIN GLULISINE Drug: PREMIXED INSULIN	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A 24-week, Open, Multicenter, Comparative Study of 2 Strategies (Including Insulin Glargine Versus Premixed Insulin) for the Therapeutic Management of Patients With Type 2 Diabetes Failing Oral Agents

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2 Hypoglycemia

Drug Information available for: Insulin human Insulin glargine Insulin glulisine

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

Percentage of patients with Glycosylated Haemoglobin (HbA1c) <7% with no documented symptomatic hypoglycemia (confirmed by a Plasma Glucose (PG) ≤ 56 mg/dL [3.1 mmol/L] [ Time Frame: From baseline (visit 2, week 0) to visit 14 (week 24) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

7-point plasma glucose (PG) profile recorded on 3 consecutive days [ Time Frame: From baseline (visit 2, week 0) to visit 14 (week 24) ] [ Designated as safety issue: No ]
Self-monitored PG (Plasma Glucose) values over 3 consecutive days [ Time Frame: before visit 4 (week 2) ] [ Designated as safety issue: No ]
Self-monitored PG (Plasma Glucose) values over 3 consecutive days [ Time Frame: before visit 8 (week 6) ] [ Designated as safety issue: No ]
Self-monitored PG (Plasma Glucose) values over 3 consecutive days [ Time Frame: before visit 12 (week 16) ] [ Designated as safety issue: No ]
Weight and supine blood pressure [ Time Frame: From baseline (visit 2, week 0) to visit 14 (week 24) ] [ Designated as safety issue: No ]
Insulin doses of the day before each visit [ Time Frame: from visit 3 (week 1) to visit 14 (week 24) ] [ Designated as safety issue: No ]
Biochemistry and lipid profile [ Time Frame: From baseline (visit 2, week 0) to visit 14 (week 24) ] [ Designated as safety issue: No ]

Enrollment:	934
Study Start Date:	February 2010
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Insulin glargine 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.	Drug: INSULIN GLARGINE Pharmaceutical form: solution for injection Route of administration: sub-cutaneous injection Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 ml) Drug: INSULIN GLULISINE Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 mL)
Experimental: Premixed insulin 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	Drug: PREMIXED INSULIN Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: - 30% soluble insulin aspart and 70 % protamine-crystallised insulin aspart in pre-filled Flexpen for all the countries except Mexico 25 % insulin lispro solution and 75% insulin lispro protamine in cartridges for Humapen Luxura for Mexico only

Arms

Assigned Interventions

Experimental: Insulin glargine

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.

Drug: INSULIN GLARGINE

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous injection Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 ml)

Drug: INSULIN GLULISINE

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: 100 Units/mL solution for injection in a pre-filled SoloStar pen (3 mL)

Experimental: Premixed insulin

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

Drug: PREMIXED INSULIN

Pharmaceutical form: solution for injection Route of administration: sub-cutaneous Dose regimen: - 30% soluble insulin aspart and 70 % protamine-crystallised insulin aspart in pre-filled Flexpen for all the countries except Mexico

25 % insulin lispro solution and 75% insulin lispro protamine in cartridges for Humapen Luxura for Mexico only

Eligibility

Ages Eligible for Study:	35 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01121835

Show 96 Study Locations

Sponsors and Collaborators

Sanofi

Investigators

Study Director:

Clinical Sciences & Operations

Sanofi

More Information

No publications provided

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT01121835 History of Changes
Other Study ID Numbers:	LANTU_C_04589, 2009-018172-33, U1111-1116-9859
Study First Received:	May 6, 2010
Last Updated:	April 2, 2013
Health Authority:	Mexico: National Institute of Public Health, Health Secretariat

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glargine

Insulin glulisine
Insulin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013

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