Clinical trial NCT00174668 (phase 3, status: completed)
Conditions: diabetes mellitus, type 2
ICD codes: E11.65, E11.9, E11.21, E11.36, E11.41, E11.42, E11.44
Drugs: insulin glulisine, insulin therapy, insulin glargine
SMILES: [Na+].[Na+].[O-]P([O-])(F)=O, [Na+].[Na+].[O-]P([O-])(F)=O, [Na+].[Na+].[O-]P([O-])(F)=O
Eligibility criteria:

        Inclusion criteria :

        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.

        Exclusion criteria :

        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.

          -  History of drug or alcohol abuse within the last 2 years or current addiction to
             substances of abuse.

          -  Night shift workers.

          -  Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to
             return for follow-up visits, and unlikelihood of completing the study.

          -  Subject is the investigator or any subinvestigator, research assistant, pharmacist,
             study coordinator, other staff or relative thereof directly involved in the conduct of
             the protocol.

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