Insulin Glulisine in Diabetes Mellitus, Type 2

NCT00174668 | Completed Phase 3

• 2 other identifiers: HMR1964A_3504EUDRACT # : 2004-001287-49
• Study Type: interventional
• Target: 311
• Locations: 15 countries
• Sites: 15

Brief Summary

Primary objective: The primary study objective is to demonstrate superior efficacy of an intensified insulin regimen with insulin glulisine and insulin glargine to a two-injection conventional insulin regimen in terms of change in glycated hemoglobin A1c (HbA1c), from baseline to endpoint. Secondary objectives: Secondary study objectives are to compare the intensified insulin regimen with insulin glulisine and insulin glargine to a two-injection conventional insulin regimen in terms of blood glucose (BG) values (fasting, pre-/postprandial (ppBG), nocturnal, mean daily, fasting plasma glucose), daily BG profiles, BG and HbA1c response rates (predefined), hypoglycemic events, adverse events, change of late diabetes complications, weight, body-mass-index, course of total daily insulin dose and adjustment, blood lipid profile, microalbuminuria, standard lab and quality of life/treatment satisfaction.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (6)

• HbA1c

  From baseline to study endpoint

• Self monitored BG (SMBG) values

  During the whole treatment phase

• Body weight/body mass index (BMI)

  From baseline to study endpoint and all other visits

• Fasting blood lipid profile

  From baseline to study endpoint and all other visits

• Urine albumin

  From baseline to study endpoint and all other visits

• Total daily insulin dose

  From baseline to study endpoint

Secondary Outcomes (4)

• Adverse events

  Throughout the study,

• Standard laboratory tests

  From baseline to study endpoint and all other visits

• Vital signs

  From baseline to study endpoint and all other visits

• Physical examination

  From baseline to study endpoint and all other visits

Study Arms (2)

1

EXPERIMENTAL

Mealtime insulin glulisine 3x daily and insulin glargine 1 x daily subcutaneously

Drug: Insulin Glulisine; Drug: Insulin Glargine

2

ACTIVE COMPARATOR

Two daily injection conventional insulin therapy

Drug: Insulin Therapy

Interventions

Insulin Glulisine DRUG

insulin glulisine 3 x daily (TID) subcutaneously 15 min before the start of a meal

1

Insulin Therapy DRUG

NPH (70%) plus regular insulin or insulin aspart (30%)

2

Insulin Glargine DRUG

1 x daily (OD) subcutaneously at any time (but every day at the same time) according to BG

1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects meeting all of the following criteria will be considered for enrollment into the study:
• Type 2 diabetes mellitus, as defined by the American Diabetes Association for at least five years, treated with insulin for at least 6 months (no history of ketoacidosis).
• HbA1c between 7.5% and 11.0%, inclusive at both pre-screening and pre-randomization (week -2).
• For at least 3 months prior to week -8 visit, subjects must have been on a stable insulin regimen with two daily s.c. injections of premixed insulin: NPH plus regular insulin or NPH plus rapid acting insulin (insulin lispro or insulin aspart) in a mixture of 70/30 or 75/25. "Stable" means no change in regimen and no more than 30 % change in dose. Optionally, the subject can have been treated in addition with metformin according to its current official product information leaflet, treatment with other oral blood glucose lowering drugs is not allowed.
• Documentation of a full ophthalmologic exam (incl. fundoscopy)during the 6 months prior to randomization.
• Women are either not of childbearing potential (surgically sterile, or postmenopausal for more than 2 years). Women of childbearing potential must not be pregnant and agree to use a reliable contraceptive measure for the duration of the study. Reliable contraceptive measures include the following: systemic contraceptive (oral, implant, injections), diaphragm with intravaginal spermicide, cervical cap, intrauterine device or condom with spermicide.
• Willing and able to perform specified home blood glucose monitoring and to otherwise comply with study protocol requirements.
• Willing to change from a twice daily insulin regimen to a regimen requiring four daily insulin injections.
• Provision of signed and dated informed consent prior to any study procedures."Prescreening" informed consent, obtained in writing for all subjects, may be used during screening, but full study-specific informed consent must be obtained in writing for all subjects after any post-screening procedures.

You may not qualify if:

• Subjects presenting with any of the following will not be included in the study:
• Two or more severe hypoglycemic episodes within the past 3 months, or any hospitalization or emergency room visit due to poor diabetic control within the past 3 months prior to randomization.
• History of hypoglycemia unawareness.
• Impaired hepatic function, as shown by, but not limited to, ALAT (SGPT) or ASAT (SGOT) above 2x the upper limit of normal as measured at visit 1.
• Impaired renal function, as shown by, but not limited to, serum creatinine \> 177 mmol/l (\> 2 mg/dl) as measured at visit 1 (if no lower values due to individual metformin intake are required) or current renal dialysis.
• Body mass index (BMI) \> 38 kg/m2.
• Any other clinically significant abnormalities on screening laboratory evaluation (unless discussed with the monitor and approved by the study management).
• Active proliferative diabetic retinopathy, as defined by the application of focal or panretinal photocoagulation or vitrectomy, in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require surgical treatment (including laser photocoagulation) during the study.
• History of hypersensitivity to insulin or insulin analogues or any of the excipients in the HMR 1964 formulation.
• Donation of blood or transfusion during the 2 months prior to the screening visit.
• Pregnant or lactating women, or women planning to become pregnant during the study.
• Treatment with any investigational drug in the last month before visit 1 (screening).
• Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study.
• Any clinically significant major organ system disease such as relevant cardiovascular, gastrointestinal, hepatic, neurologic, endocrine, hematologic or other major systemic diseases making implementation of the protocol or interpretation of the study results difficult.
• Treatment or likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (15)

Sanofi-Aventis

North Ryde, Australia

Location

Sanofi-Aventis

Brussels, Belgium

Location

Sanofi-Aventis

Prague, Czechia

Location

Sanofi-Aventis

Paris, France

Location

Sanofi-Aventis

Berlin, Germany

Location

Sanofi-Aventis

Milan, Italy

Location

Sanofi-Aventis

Gouda, Netherlands

Location

Sanofi-Aventis

Warsaw, Poland

Location

Sanofi-Aventis

Porto Salvo, Portugal

Location

Sanofi-aventis

Bucharest, Romania

Location

Sanofi-Aventis

Bratislava, Slovakia

Location

Sanofi-Aventis

Barcelona, Spain

Location

Sanofi-Aventis

Stockholm, Sweden

Location

Sanofi-Aventis

Meyrin, Switzerland

Location

Sanofi-Aventis

Guildford, United Kingdom

Location

Related Publications (1)

• Fritsche A, Hahn A, Landgraf W, Haring HU. Incidence of Hypoglycaemia in Patients with Type 2 Diabetes - A Subgroup Analysis from the GINGER study. Eur Endocrinol. 2013 Mar;9(1):1-3. doi: 10.17925/EE.2013.09.01.1. Epub 2013 Apr 4.

  PMID: 30349602 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

insulin glulisine; Convulsive Therapy; Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Valérie Pilorget, MD

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 15, 2005
• Study Start: November 1, 2004
• Primary Completion: November 1, 2007
• Last Updated: September 15, 2009

Record last verified: 2009-09

Locations

BE (1); SL (1); CH (1); PT (1); IT (1); AU (1); CZ (1); NL (1); PL (1); RO (1); SE (1); DE (1); GB (1); FR (1); ES (1)