Efficacy and Safety of Toujeo® Versus Tresiba® in Insulin-Naive Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Antihyperglycemic Drug(s) ± GLP-1 Receptor Agonist

ID: NCT02738151
Status: Completed
Phase: Phase 4
Start Date: May 19, 2016
First Submitted: March 31, 2016
Last Updated: February 20, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Sanofi
Location: Bulgaria, Croatia, Czechia, Denmark, France, Greece, Hungary, Israel, Italy, Romania, Serbia, Slovakia, Sweden, Switzerland, United Kingdom, United States
Conditions: Diabetes Mellitus, Type 2
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Study Description

Brief Summary

Primary Objective:

To demonstrate the noninferiority in the efficacy of Toujeo® to Tresiba® in glycated hemoglobin (HbA1c) change.

Secondary Objectives:

- To assess the effects of the insulin Toujeo® in comparison with insulin Tresiba® on:

- Change in Fasting plasma glucose (FPG);

- Change in Fasting self-monitored plasma glucose (SMPG) and 4-point SMPG and 8-point SMPG profile;

- Percentage of patients reaching HbA1c targets <7% or ≤6.5%;

- Percentage of patients reaching HbA1c targets <7% or ≤6.5% without severe and/or confirmed hypoglycemia

- Percentage of patients requiring rescue therapy.

- To assess the frequency of occurrence and diurnal distribution of hypoglycemia by American Diabetes Association (ADA) category of hypoglycemia.

- To assess the safety in each treatment group.

- To assess the treatment effects in each treatment group on Patient Reported Outcomes (PRO).

Detailed Description

The maximum study duration per patient will be approximately 27 weeks: an up to 2-week screening period, a 24-week randomized treatment period, and a 7-day posttreatment safety follow-up period.
Condition or disease Intervention/treatment Phase

Diabetes Mellitus, Type 2

Drug: INSULIN GLARGINE (U300)
Other Names
HOE901, Toujeo
Drug: Insulin degludec
Other Names
Tresiba
Drug: GLP-1 receptor agonist
Other Names
Drug: Glimepiride
Other Names
Drug: Metformin
Other Names
Phase 4

Tracking Information

First Submitted DateMarch 31, 2016
Last Update Posted DateFebruary 20, 2018
Start DateMay 19, 2016
Actual Completion DateAugust 15, 2017
Primary Completion DateAugust 15, 2017
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change from baseline in HbA1c [Time Frame: Baseline to Week 24]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Change from baseline in HbA1c [Time Frame: Baseline to Week 12]

  • Change in FPG from baseline [Time Frame: Baseline to Week 12 and Week 24]

  • Change in fasting self-monitoring plasma glucose (SMPG) from baseline [Time Frame: Baseline to Week 12 and Week 24]

  • Change in 4-point and 8-point SMPG profiles per time-point from baseline [Time Frame: Baseline to Week 12 and Week 24]

  • Change of mean 24-hour plasma glucose from baseline [Time Frame: Baseline to Week 12 and Week 24]

  • Change in variability of fasting SMPG from baseline [Time Frame: Baseline to Week 12 and Week 24]

  • Change in variability of 24-hour plasma glucose from baseline [Time Frame: Baseline to Week 12 and Week 24]

  • Percentage (%) of patients reaching target HbA1c <7% and ≤6.5% [Time Frame: Baseline to Week 12 and Week 24]

  • Percentage (%) of patients reaching target HbA1c <7% and ≤6.5% without severe and/or confirmed hypoglycemia [Time Frame: Baseline to Week 12 and Week 24]

  • Percentage (%) of patients with sulphonylurea or meglitinide dose reduction due to hypoglycemia [Time Frame: Baseline to Week 24]

  • Percentage of patients requiring a rescue therapy [Time Frame: Baseline to Week 24]

  • Change in basal insulin dose (U and U/kg body weight) from baseline [Time Frame: Baseline to Week 12 and Week 24]

  • Percentage of patients reporting hypoglycemia event per ADA classification [Time Frame: Baseline to Week 24]

  • Event rate of hypoglycemia per ADA classification [Time Frame: Baseline to Week 24]

  • Percentage (%) of patients experiencing adverse events [Time Frame: Baseline to Week 24]

  • Change in Patient Report Outcomes scores [Time Frame: Baseline to Week 12 and Week 24]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEfficacy and Safety of Toujeo® Versus Tresiba® in Insulin-Naive Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Antihyperglycemic Drug(s) ± GLP-1 Receptor Agonist
Official TitleA 24-week, Multicenter, Randomized, Open-label, Parallel-group StudyComparing the Efficacy and Safety of Toujeo® and Tresiba® in Insulin-NaivePatients With Type 2 Diabetes Mellitus Not Adequately Controlled With OralAntihyperglycemic Drug(s) GLP-1 Receptor Agonist
Brief Summary

Primary Objective:

To demonstrate the noninferiority in the efficacy of Toujeo® to Tresiba® in glycated hemoglobin (HbA1c) change.

Secondary Objectives:

- To assess the effects of the insulin Toujeo® in comparison with insulin Tresiba® on:

- Change in Fasting plasma glucose (FPG);

- Change in Fasting self-monitored plasma glucose (SMPG) and 4-point SMPG and 8-point SMPG profile;

- Percentage of patients reaching HbA1c targets <7% or ≤6.5%;

- Percentage of patients reaching HbA1c targets <7% or ≤6.5% without severe and/or confirmed hypoglycemia

- Percentage of patients requiring rescue therapy.

- To assess the frequency of occurrence and diurnal distribution of hypoglycemia by American Diabetes Association (ADA) category of hypoglycemia.

- To assess the safety in each treatment group.

- To assess the treatment effects in each treatment group on Patient Reported Outcomes (PRO).

Detailed Description

The maximum study duration per patient will be approximately 27 weeks: an up to 2-week screening period, a 24-week randomized treatment period, and a 7-day posttreatment safety follow-up period.

Study TypeInterventional
Study PhasePhase 4
Estimated Enrollment
929
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Diabetes Mellitus, Type 2
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: INSULIN GLARGINE (U300)

Pharmaceutical form: solution Route of administration: subcutaneous

Other Names
HOE901, Toujeo
Drug: Insulin degludec

Pharmaceutical form: solution Route of administration: subcutaneous

Other Names
Tresiba
Drug: GLP-1 receptor agonist

Pharmaceutical form: solution Route of administration: subcutaneous

Other Names
Drug: Glimepiride

Pharmaceutical form: tablet Route of administration: oral

Other Names
Drug: Metformin

Pharmaceutical form: tablet Route of administration: oral

Other Names
Study Groups/Cohorts
Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.

Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.

Study Arms
Active Comparator Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.
Drug : Insulin degludec
Pharmaceutical form: solution Route of administration: subcutaneous

Active Comparator Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.
Drug : GLP-1 receptor agonist
Pharmaceutical form: solution Route of administration: subcutaneous

Active Comparator Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.
Drug : Glimepiride
Pharmaceutical form: tablet Route of administration: oral

Active Comparator Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.
Drug : Metformin
Pharmaceutical form: tablet Route of administration: oral

Experimental Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.
Drug : INSULIN GLARGINE (U300)
Pharmaceutical form: solution Route of administration: subcutaneous

Experimental Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.
Drug : Metformin
Pharmaceutical form: tablet Route of administration: oral

Experimental Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.
Drug : Glimepiride
Pharmaceutical form: tablet Route of administration: oral

Experimental Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.
Drug : GLP-1 receptor agonist
Pharmaceutical form: solution Route of administration: subcutaneous

Arm Intervention/Treatment
Active Comparator Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.
Drug : Insulin degludec
Active Comparator Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.
Drug : GLP-1 receptor agonist
Active Comparator Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.
Drug : Glimepiride
Active Comparator Insulin degludec
Insulin degludec is self-administered OD. Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (OADs and GLP-1 receptor agonist) during the study period.
Drug : Metformin
Experimental Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.
Drug : INSULIN GLARGINE (U300)
Experimental Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.
Drug : Metformin
Experimental Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.
Drug : Glimepiride
Experimental Insulin glargine (U300)
Insulin glargine (U300) is self-administered once daily (OD). Treatment will be initiated and individually adjusted at least weekly according to fasting SMPG target. Subjects should continue their background noninsulin antidiabetic treatment (oral antihyperglycemic drugs[OADs] and glucagon like peptide-1[GLP-1] receptor agonist) during the study period.
Drug : GLP-1 receptor agonist

Recruitment Information

Recruitment Status:Completed
Enrollment929
Completion DateAugust 15, 2017
Eligibility Criteria: Inclusion criteria :
- Adult patients with type 2 diabetes mellitus (T2DM) inadequately controlled with OADs therapy with/without GLP-1 receptor agonist at stable dose for at least 3 months.
- Signed written informed consent.
Exclusion criteria:
- Age <18 years.
- HbA1c <7.5% or >10.5% (at screening visit). Body mass index (BMI) <25 kg/m^2 or >40 kg/m^2.
- History of T2DM for less than 1 year before screening.
- Less than 6 months before screening on OADs treatment and GLP-1 receptor agonist (if taken).
- Current or previous insulin use except for a maximum of 8 consecutive days or totally 15 days (eg, acute illness, surgery) during the last year prior to screening.
- Initiation of new glucose-lowering medications and/or weight loss drug in the last 3 months before screening visit.
- Patient receiving only noninsulin antihyperglycemic drugs not approved for combination with insulin according to local labelling/local treatment guideline.
- History of hypoglycemia unawareness or repeated episodes of severe hypoglycemia or metabolic acidosis, including hospitalization for diabetic ketoacidosis during the last 12 months prior to screening.
- Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (eg, laser, surgical treatment, or injectable drugs) during the study period.
- End stage renal disease.
- Any acute or chronic condition that in the opinion of Investigator would affect the patient safety, compliance, or study results.
- Any contraindication to use of Toujeo® or Tresiba® as defined in the national product label, hypersensitivity to Toujeo® or Tresiba® active ingredients or one of the excipients.
- Pregnant or breast-feeding women.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
Bulgaria
Croatia
Czechia
Denmark
France
Greece
Hungary
Israel
Italy
Romania
Serbia
Slovakia
Sweden
Switzerland
United Kingdom
United States
Czech Republic

Administrative Information

NCT Number:NCT02738151
Other Study ID Numbers
LPS14584
2015-005101-36
U1111-1177-6327
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Sanofi
Collaborators
Not Available
Investigators
Study Director
Clinical Sciences & Operations
Sanofi