Type 1 Diabetes MellitusPhase 4inRangeNCT04075513
Comparison of Glucose Values and Variability Between TOUJEO and TRESIBA During Continuous Glucose Monitoring in Type 1 Diabetes Patients
A Phase 4 study testing Insulin glargine, 300 U/ml, Insulin degludec, 100U/ml and Background therapy: Rapid acting insulin analogs in people with Type 1 Diabetes Mellitus, run by Sanofi at 7 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Insulin glargine, 300 U/ml, Insulin degludec, 100U/ml and Background therapy: Rapid acting insulin analogs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 343 participants
- Where
- 7 sitesin 7 countries
- Study dates
- 9 Oct 2019to 16 Sep 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
7 sites in 7 countries.
7 sites in 7 countries
United Kingdom1 site
Investigational site United Kingdom
United Kingdom
About this study
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
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.
Read the 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.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Insulin glargine, 300 U/ml, Insulin degludec, 100U/ml, Background therapy: Rapid acting insulin analogs
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin glargine, 300 U/mlDrug
Also called Toujeo, HOE901-U300
Pharmaceutical form: solution for injection in a prefilled pen
Route of administration: SC injection
Insulin degludec, 100U/mlDrug
Also called Tresiba
Pharmaceutical form: solution for injection in a prefilled pen
Route of administration: SC injection
Background therapy: Rapid acting insulin analogsDrug
Route of administration: SC injection
| Study group | Role | What they receive |
|---|---|---|
| Toujeo | Experimental | 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. Receives: Drug: Insulin glargine, 300 U/ml; Drug: Background therapy: Rapid acting insulin analogs |
| Tresiba | Active comparator | Tresiba (Insulin Degludec, 100U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog. Receives: Drug: Insulin degludec, 100U/ml; Drug: Background therapy: Rapid acting insulin analogs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During Week 10 up to Week 12
Secondary outcomes (11)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2019
- Study start9 Oct 2019
- Primary completion16 Sep 2021
- Study completion16 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 343 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04075513
- Sponsor's protocol ID
- LPS14947
- Other IDs
- 2017-002756-91, U1111-1197-8171, 2017
- Acronym
- inRange
- Status last verified
- Oct 2022
- First submitted
- 29 Aug 2019
- Last updated
- 14 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
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.
PubMed 32100192
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04075513
- Acronym / sponsor ID
- inRange / LPS14947
- Conditions
- Type 1 Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 343 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2019 (actual)
- Primary completion
- 16 Sep 2021 (actual)
- Study completion
- 16 Sep 2021 (actual)
- First posted
- 30 Aug 2019 (actual)
- Results
- Posted 14 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Toujeo | Experimental | Drug: Insulin glargine, 300 U/ml, Drug: Background therapy: Rapid acting insulin analogsToujeo (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 | Active comparator | Drug: Insulin degludec, 100U/ml, Drug: Background therapy: Rapid acting insulin analogsTresiba (Insulin Degludec, 100U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin glargine, 300 U/mlAlso: Toujeo, HOE901-U300Pharmaceutical form: solution for injection in a prefilled pen Route of administration: SC injection | Drug | Toujeo |
| Insulin degludec, 100U/mlAlso: TresibaPharmaceutical form: solution for injection in a prefilled pen Route of administration: SC injection | Drug | Tresiba |
| Background therapy: Rapid acting insulin analogsRoute of administration: SC injection | Drug | Toujeo, Tresiba |
Primary outcome
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
Time frame: During Week 10 up to Week 12
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.
11 secondary outcomes
Glucose Total Coefficient of Variation (CV%)
Time frame: 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
Time frame: During Week 10 up to Week 12
Glucose Within-day CV% and Between-day CV%
Time frame: During Week 10 up to Week 12
Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 12
Time frame: Baseline, Week 12
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
Time frame: Baseline, Week 12
Percentage of Time With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night)
Time frame: During Week 10 up to Week 12
Mean Hours Per Day With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night)
Time frame: During Week 10 up to Week 12
Percentage of Time With Glucose Level >180 Milligrams Per Deciliter
Time frame: During Week 10 up to Week 12
Mean Hours Per Day With Glucose Level >180 Milligrams Per Deciliter
Time frame: During Week 10 up to Week 12
Number of Participants With at Least One Hypoglycemic Event During the On-treatment Period
Time frame: 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
Time frame: From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32100192Battelino 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.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
7 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Insulin glargine, 300 U/ml, Insulin degludec, 100U/ml and Background therapy: Rapid acting insulin analogs in people with Type 1 Diabetes Mellitus, run by Sanofi at 7 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Brazil, Germany, Hungary, Netherlands and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: During Week 10 up to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04075513, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2022.