Back to resultsComparison of Glucose Values and Variability Between TOUJEO and TRESIBA During Continuous Glucose Monitoring in Type 1 Diabetes Patients (inRange)
Primary Purpose
Type 1 Diabetes Mellitus
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Insulin glargine, 300 U/ml
Insulin degludec, 100U/ml
Background therapy: Rapid acting insulin analogs
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus
Eligibility Criteria
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.
Sites / Locations
- United States
- Investigational site BRAZIL
- Investigational site Germany
- Investigational site Hungary
- Investigational site Netherlands
- Investigational site Turkey
- Investigational site United Kingdom
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Toujeo
Tresiba
Arm Description
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.
Tresiba (Insulin Degludec, 100U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04075513
Brief Title
Comparison of Glucose Values and Variability Between TOUJEO and TRESIBA During Continuous Glucose Monitoring in Type 1 Diabetes Patients
Acronym
inRange
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
October 9, 2019 (Actual)
Primary Completion Date
September 16, 2021 (Actual)
Study Completion Date
September 16, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
343 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Toujeo
Arm Type
Experimental
Arm Description
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.
Arm Title
Tresiba
Arm Type
Active Comparator
Arm Description
Tresiba (Insulin Degludec, 100U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Intervention Type
Drug
Intervention Name(s)
Insulin glargine, 300 U/ml
Other Intervention Name(s)
Toujeo, HOE901-U300
Intervention Description
Pharmaceutical form: solution for injection in a prefilled pen
Route of administration: SC injection
Intervention Type
Drug
Intervention Name(s)
Insulin degludec, 100U/ml
Other Intervention Name(s)
Tresiba
Intervention Description
Pharmaceutical form: solution for injection in a prefilled pen
Route of administration: SC injection
Intervention Type
Drug
Intervention Name(s)
Background therapy: Rapid acting insulin analogs
Intervention Description
Route of administration: SC injection
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
During Week 10 up to Week 12
Secondary Outcome Measure Information:
Title
Glucose Total Coefficient of Variation (CV%)
Description
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.
Time Frame
During Week 10 up to Week 12
Title
Percentage of Time of Glucose Concentration Within the Target Range of >=70 to <=180 Milligrams Per Deciliter: Superiority Analysis
Description
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.
Time Frame
During Week 10 up to Week 12
Title
Glucose Within-day CV% and Between-day CV%
Description
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.
Time Frame
During Week 10 up to Week 12
Title
Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Percentage of Time With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night)
Description
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.
Time Frame
During Week 10 up to Week 12
Title
Mean Hours Per Day With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night)
Description
"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.
Time Frame
During Week 10 up to Week 12
Title
Percentage of Time With Glucose Level >180 Milligrams Per Deciliter
Description
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.
Time Frame
During Week 10 up to Week 12
Title
Mean Hours Per Day With Glucose Level >180 Milligrams Per Deciliter
Description
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.
Time Frame
During Week 10 up to Week 12
Title
Number of Participants With at Least One Hypoglycemic Event During the On-treatment Period
Description
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.
Time Frame
From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days)
Title
Number of Hypoglycemic Events Per Participant Year During the On-treatment Period
Description
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.
Time Frame
From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75000
Country
United States
Facility Name
Investigational site BRAZIL
City
Brazil
Country
Brazil
Facility Name
Investigational site Germany
City
Germany
Country
Germany
Facility Name
Investigational site Hungary
City
Hungary
Country
Hungary
Facility Name
Investigational site Netherlands
City
Netherlands
Country
Netherlands
Facility Name
Investigational site Turkey
City
Turkey
Country
Turkey
Facility Name
Investigational site United Kingdom
City
United Kingdom
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
32100192
Citation
Battelino T, Bosnyak Z, Danne T, Mukherjee B, Edelman S, Pilorget V, Choudhary P, Renard E, Bergenstal R. InRange: Comparison of the Second-Generation Basal Insulin Analogues Glargine 300 U/mL and Degludec 100 U/mL in Persons with Type 1 Diabetes Using Continuous Glucose Monitoring-Study Design. Diabetes Ther. 2020 Apr;11(4):1017-1027. doi: 10.1007/s13300-020-00781-6. Epub 2020 Feb 25. Erratum In: Diabetes Ther. 2020 Jul;11(7):1607-1608. Diabetes Ther. 2020 Aug;11(8):1907-1908.
Results Reference
derived
Learn more about this trial
Comparison of Glucose Values and Variability Between TOUJEO and TRESIBA During Continuous Glucose Monitoring in Type 1 Diabetes Patients
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