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Insulin glulisine

Phase 3

Diabetes Mellitus | Small molecule | Metabolic |Sanofi|Last Updated: Apr 25, 2022

Target and mechanism

ModalitySmall molecule

Also known as Insulin glulisine (U300), Insulin glulisine (HMR1964), Insulin glulisine QD, Insulin Glulisine (HMR1964)

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLED
Total Trials2
Total Enrollment485

FDA Designations

No designations recorded

Clinical trial landscape

Insulin glulisine · 20 trials · 11 indications

Phase 3 13Phase 1 7
NCT00467376Insulin Glulisine, Insulin Lispro and Insulin Glargine in Type 1 or 2 Diabetes MellitusDiabetes Mellitus
COMPLETED485 Analytics
NCT00272064ELEONOR STUDY: Insulin Glulisine in Type 2 Diabetes Mellitus.Diabetes Mellitus, Type 2
COMPLETED352 Analytics
NCT00271284Efficacy Study on the Control of Blood Glucose Concentration in Type 1 Diabetic PatientsDiabetes Mellitus, Type 1
COMPLETED88 Analytics
NCT00115570Comparison of the Ability of Glulisine With Lispro to Control Type 1 Diabetes Mellitus in Children and AdolescentsDiabetes Mellitus, Insulin-Dependent
COMPLETED572 Analytics
NCT00397553Insulin Glulisine, Diabetes Mellitus Type 1Diabetes Mellitus, Type 1
COMPLETED104 Analytics
NCT00290979Efficacy and Safety of Insulin Glulisine in Type 1 Diabetes MellitusDiabetes Mellitus, Type 1
COMPLETED250 Analytics
NCT00174668Insulin Glulisine in Diabetes Mellitus, Type 2Diabetes Mellitus, Type 2
COMPLETED311 Analytics
NCT00135096Insulin Glulisine Administered Pre-meal Versus Post-meal in Adult Subjects With Type 2 Diabetes Mellitus Receiving Insulin Glargine as Basal InsulinDiabetes Mellitus, Type 2
COMPLETED345 Analytics
NCT00135083Variable Bolus Regimen 1-2-3 for Type 2 Diabetes MellitusDiabetes Mellitus, Type 2
COMPLETED347 Analytics
NCT00272012OPAL - Insulin Glulisine, Diabetes MellitusDiabetes Mellitus Type 2
COMPLETED396 Analytics
PHASE3COMPLETED
Insulin Glulisine, Insulin Lispro and Insulin Glargine in Type 1 or 2 Diabetes Mellitus
Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
ELEONOR STUDY: Insulin Glulisine in Type 2 Diabetes Mellitus.
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
Efficacy Study on the Control of Blood Glucose Concentration in Type 1 Diabetic Patients
Diabetes Mellitus, Type 1Unlock trial analytics
PHASE3COMPLETED
Comparison of the Ability of Glulisine With Lispro to Control Type 1 Diabetes Mellitus in Children and Adolescents
Diabetes Mellitus, Insulin-DependentUnlock trial analytics
PHASE3COMPLETED
Insulin Glulisine, Diabetes Mellitus Type 1
Diabetes Mellitus, Type 1Unlock trial analytics
PHASE3COMPLETED
Efficacy and Safety of Insulin Glulisine in Type 1 Diabetes Mellitus
Diabetes Mellitus, Type 1Unlock trial analytics
PHASE3COMPLETED
Insulin Glulisine in Diabetes Mellitus, Type 2
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
Insulin Glulisine Administered Pre-meal Versus Post-meal in Adult Subjects With Type 2 Diabetes Mellitus Receiving Insulin Glargine as Basal Insulin
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
Variable Bolus Regimen 1-2-3 for Type 2 Diabetes Mellitus
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
OPAL - Insulin Glulisine, Diabetes Mellitus
Diabetes Mellitus Type 2Unlock trial analytics

Study Endpoints

Primary Endpoints

Hypoglycemic episodes
From the beginning to end of the study
Change in HbA1c
From baseline to endpoint
Adverse events
From the beginning to the end of study
Changes of glycosilated haemoglobin (HbA1c)
At least 12 weeks from baseline (visit 3)
Efficacy data : fasting blood glucose concentration
read daily during the last 2 months of each period
Change in total glycated hemoglobin measured as HbA1c equivalents (GHb )from baseline to endpoint
week 26 or last observed treatment
HbA1c
52 weeks
Non-inferiority in the efficacy and safety of HMR1964 as compared with Insulin lispro
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
Compare change in weight from baseline to study week 52 in the per-protocol population of premeal Apidra vs postmeal Apidra, in patients receiving Lantus as basal insulin
52 weeks
To show non-inferiority between treatment groups (insulin glargine plus insulin glulisine administered once a day, twice a day, or 3 times a day) in the change in glycemic control as measured by hemoglobin A1C.
From baseline to study week 24.
Change in HbA1c.
from baseline to study endpoint.
Compare the change in glycemic control (as measured by A1c) from baseline to endpoint of fixed dose bolus regimen vs. variable bolus regimen based on carbohydrate count
Efficacy: change in HbA1C from baseline to endpoint (superiority of HMR1964 and OHA combination therapy as compared to OHA therapy, superiority of HMR1964 mono-therapy as compared to OHA therapy)
Safety of HMR1964
Frequency of catheter occlusions
Assessment of PK parameter: maximum observed insulin concentration
10 hours
Assessment of PK parameter: area under the concentration time curve
10 hours
Area under the plasma glucose concentration curve (AUC) between 0 and 1 hour after insulin injection AUC(0-1h)
At day 1 of each treatment period
Maximum plasma glucose concentration (GLUmax, mmol/L)
During the Study Conduct
Maximum plasma glucose excursion (baseline subtracted glucose concentration, ΔGLUmax, mmol/L)
during the study conduct
Time to GLUmax (Tmax, min)
during the study conduct
serum insulin concentrations
During the Study Conduct
To evaluate the serum insulin glulisine concentration and insulin lispro concentration
During the Study Conduct
Outcome measures: Glucose infusion rate, insulin concentrations.
Outcome:In T1DM, glulisine, like RHI, displays dose proportionality in exposure over the dose range 0.075 to 0.3 U/kg, which partly only translates into dose proportionality in glucodynamics.
Outcome measures: Post-prandial glucose and insulin concentrations. Outcome: In T1DM, insulin glulisine provides a better mimic of the physiological postprandial glucose disposal than RHI.

Secondary Endpoints

Change in HbA1c
From baseline to weeks 12
blood glucose parameters, hypoglycemic episodes and dosage of the mealtime and Lantus.
from baseline to week 12
Changes in fasting plasma glucose
At each visit
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
1EXPERIMENTALAdministration of Insulin Glulisine
2ACTIVE_COMPARATORAdministration of Lispro
IEXPERIMENTAL -
IIACTIVE_COMPARATOR -
Insulin GlulisineEXPERIMENTALInsulin Glulisine (100UI/ml), at least twice daily, in association with basal insulin therapy (NPH insulin or insulin glargine for a maximum of 26 weeks
Insulin LisproACTIVE_COMPARATORInsulin Lispro (100UI/ml) Subcutaneous (SC) injection , at least twice daily, in association with basal insulin therapy (NPH insulin or insulin glargine ) for a maximum of 30 weeks
3EXPERIMENTALTwice daily: * Insulin glulisine Dosing: Supper, Lunch, Breakfast * Monitoring Needed at: Bedtime, Pre-Supper, Pre-Lunch
Insulin glulisine (U300) - Test formulationEXPERIMENTALInsulin glulisine (U300) will be given as a single subcutaneous (SC) dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
Insulin glulisine - Reference formulationACTIVE_COMPARATORInsulin glulisine (U100) will be given as a single SC dose on Day 1 of each period under fasting conditions according to the random list and assigned sequence. Glucose, insulin aspart (IV) and heparin will be used for clamp procedure. NPH insulin (if necessary) and insulin aspart (SC) will be handed out at screening to change insulin regimen and glucagon at Day 1 to treat cases of severe hypoglycemia.
insulin glulisine + insulin aspartEXPERIMENTALinsulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day)
insulin aspart + insulin glulisineEXPERIMENTALinsulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day)

Interventions

NameTypeDescription
Insulin GlulisineDRUG3 times a day before each meal
LisproDRUG3 times a day before each meal
Insulin GlargineDRUGonce daily
MetforminDRUG1000 mg b.i.d, since the qualification phase, oral
insulin glulisine / insulin glargineDRUGinsulin glargine administered subcutaneously by the patient once a day, in the evening, between 18.30 and 24.00
insulin glulisin / insulin detemirDRUGinsulin detemir administered subcutaneously by the patient once a day, in the evening, between 18.30 and 24.00
insulin lisproDRUGSubcutaneous injection
NPH insulinDRUGsubcutaneous injection twice daily
Insulin TherapyDRUGNPH (70%) plus regular insulin or insulin aspart (30%)
Insulin glulisine (HMR1964)DRUG -
Insulin glulisine (U300)DRUGPharmaceutical form: solution Route of administration: subcutaneous
Insulin aspartDRUGPharmaceutical form: solution Route of administration: intravenous/subcutaneous
GlucagonDRUGPharmaceutical form: Powder and solvent for solution for injection Route of administration: subcutaneous
GlucoseDRUGPharmaceutical form: solution Route of administration: intravenous
HeparinDRUGPharmaceutical form: solution Route of administration: intravenous
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Eligibility Criteria

Age Range18 Years to 70 Years
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: * Type 1 or type 2 diabetic patients * Measure HbA1c 6.5% to 11.0% at visit 1 * More than 3 months of continuous insulin treatment immediately prior to study entry Exclusion Criteria: * Pregnant women The above information is not intended to contain all considerations relevan...

Countries:ChinaItalyFranceUnited StatesRussiaJapanAustraliaBelgiumCzechiaGermanyNetherlandsPolandPortugalRomaniaSlovakiaSpainSwedenSwitzerlandUnited Kingdom
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