Comparison of Glucose Values and Variability Between TOUJEO and TRESIBA During Continuous Glucose Monitoring in Type 1 Diabetes Patients

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the non-inferiority of insulin glargine 300 units per milliliter (U/ml) in comparison to insulin degludec 100 U/ml on glycemic control and variability in participants with diabetes mellitus. Secondary Objective: To evaluate the glycemic control and variability parameters in each treatment group at Week 12 using Continuous Glucose Monitoring. To evaluate the safety of insulin glargine 300 U/ml in comparison to insulin degludec 100 U/ml.

Detailed Description
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The duration of the study per participant was around 18 weeks: 1 or 2 weeks of screening followed by a 4-week run-in period, a 12-week treatment period and a 2 to 4 days follow-up period.

Official Title
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A 12-week Randomized, Controlled Trial to Compare TOUJEO® and TRESIBA® in Terms of Glucose Values in Target Range and Variability During Continuous Glucose Monitoring in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin glargine, 300 U/ml
* Drug: Insulin degludec, 100U/ml
* Drug: Background therapy: Rapid acting insulin analogs


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with Type 1 Diabetes mellitus. Participants treated with multiple daily injections using basal insulin analog once daily and rapid acting insulin analogs for at least one year. HbA1c greater than or equal to (>=) 7 percent (%) (53 millimoles per mole [mmol/mol]) and less than or equal to (<=) 10% (86 mmol/mol) at screening. Exclusion criteria: Participants not on stable dose of basal insulin analog. Participants having received Toujeo or Tresiba as basal insulin within 30 days prior to screening. Participants not having used the same insulins (both basal and rapid) within 30 days prior to screening. Participants having received basal insulin dose >= 0.6 units per kilogram body weight within 30 days prior to screening. Participants having received any glucose lowering drugs (including any premixed insulins, human regular insulin as mealtime insulins, any others injectable or oral), other than basal and rapid insulin analogs, within 3 months prior to screening. End stage renal disease or on renal replacement treatment. Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months prior to screening) or planned: intravitreal injections or laser or vitrectomy surgery. Body weight change >=5 kilogram within 3 months prior to screening. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toujeo<br>Toujeo (Insulin Glargine, 300 U/ml) subcutaneous (SC) injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog. | Drug: Insulin glargine, 300 U/ml<br>* Pharmaceutical form: solution for injection in a prefilled pen Route of administration: SC injection<br>* Other names: HOE901-U300;Drug: Background therapy: Rapid acting insulin analogs<br>* Route of administration: SC injection<br>|
| Active Comparator: Tresiba<br>Tresiba (Insulin Degludec, 100U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog. | Drug: Insulin degludec, 100U/ml<br>* Pharmaceutical form: solution for injection in a prefilled pen Route of administration: SC injection<br>* Other names: Tresiba;Drug: Background therapy: Rapid acting insulin analogs<br>* Route of administration: SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Time of Glucose Concentration Within the Target Range of Greater Than or Equal to (>=) 70 to Less Than or Equal to (<=) 180 Milligrams Per Deciliter: Non-inferiority Analysis | The Continuous Glucose Monitoring (CGM) system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted least square (LS) means and standard error (SE) were obtained using analysis of covariance (ANCOVA) model on data obtained from the multiple imputations during Week 10 to Week 12. | During Week 10 up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Total Coefficient of Variation (CV%) | CV% was a measure of spread of variability relative to mean of population. For CGM glucose values, CV% was measure of glycemic variability across 20 days and calculated as ratio of standard deviation of glucose values to mean of glucose values. LS means and SE were obtained using ANCOVA model using fixed categorical effects of treatment groups (Toujeo, Tresiba), randomization stratum of screening HbA1c (<8.0% versus >=8.0%), and the continuous fixed covariate of Baseline value. | During Week 10 up to Week 12 | 
| Percentage of Time of Glucose Concentration Within the Target Range of >=70 to <=180 Milligrams Per Deciliter: Superiority Analysis | The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted LS means and SE were obtained using ANCOVA model on data obtained from the multiple imputations during Week 10 to Week 12. | During Week 10 up to Week 12 | 
| Glucose Within-day CV% and Between-day CV% | CV% was a measure of spread of variability relative to mean of population. For CGM glucose values, CV% was measure of glycemic variability across 20 days and calculated within day and between days as ratio of standard deviation of glucose values to mean of glucose values. LS mean and SE were obtained from ANCOVA model including fixed categorical effects of treatment groups (TOUJEO, TRESIBA), randomization stratum of screening HbA1c (<8.0% versus >=8.0%), and as well as, the continuous fixed covariate of Baseline value. | During Week 10 up to Week 12 | 
| Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 12 | Change in HbA1c at Week 12 was analyzed using an ANCOVA model including the fixed categorical effects of treatment groups (Toujeo, Tresiba), and the continuous fixed covariate of Baseline HbA1c value. | Baseline, Week 12 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | Change in FPG was analyzed using an ANCOVA model including the fixed categorical effects of treatment groups (Toujeo, Tresiba) and the randomization stratum of HbA1c at screening (<8.0%, >=8.0%) and the continuous fixed covariate of Baseline FPG value. | Baseline, Week 12 | 
| Percentage of Time With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night) | The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. All time represent the time between 00.00 hour to 23.59 hours and night represent the time between 00.00 hour to 05.59 hours. LS means and SE were obtained using ANCOVA model using fixed categorical effects of treatment groups (Toujeo, Tresiba), randomization stratum of screening HbA1c (<8.0% versus >=8.0%), and the continuous fixed covariate of Baseline value. | During Week 10 up to Week 12 | 
| Mean Hours Per Day With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night) | All time represent the time between 00.00 hour to 23.59 hours and night represent the time between 00.00 hour to 05.59 hours. Mean hours per day with glucose level <70 milligrams per deciliter during all time and only during night for the duration of Week 10 to Week 12 is reported in this outcome measure. | During Week 10 up to Week 12 | 
| Percentage of Time With Glucose Level >180 Milligrams Per Deciliter | The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. LS means and SE were obtained using ANCOVA model using fixed categorical effects of treatment groups (Toujeo, Tresiba), randomization stratum of screening HbA1c (<8.0% versus >=8.0%), and the continuous fixed covariate of Baseline value. | During Week 10 up to Week 12 | 
| Mean Hours Per Day With Glucose Level >180 Milligrams Per Deciliter | Mean hours per day with glucose level >180 milligrams per deciliter for the duration of Week 10 to Week 12 is reported in this outcome measure. | During Week 10 up to Week 12 | 
| Number of Participants With at Least One Hypoglycemic Event During the On-treatment Period | Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <3.9 millimoles per liter (mmol/L) (<70 milligrams per deciliter). On-treatment period was defined as the time from the first injection of IMP (included) up to 2 days after the last injection of IMP. | From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) | 
| Number of Hypoglycemic Events Per Participant Year During the On-treatment Period | Number of hypoglycemia events (any, severe and documented) per participant-year of exposure were reported. Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <3.9 mmol/L (<70 milligrams per deciliter). On-treatment period was defined as the time from the first injection of IMP (included) up to 2 days after the last injection of IMP. Total participant years = The sum of the duration of exposure for all participants, expressed in participant years. | From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) |