Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Versus GLP-1 Receptor Agonist in Patients With Type 2 Diabetes, With a FRC Extension Period

ID: NCT02787551
Status: Recruiting
Phase: Phase 3
Start Date: July 06, 2016
First Submitted: May 26, 2016
Last Updated: February 22, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Sanofi
Location: Canada, Estonia, Germany, Israel, Italy, Romania, Slovakia, Spain, United States
Conditions: Type 2 Diabetes Mellitus
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Study Description

Brief Summary

Primary Objective:

To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) versus GLP-1 receptor agonist (GLP-1 RA) in hemoglobin A1c (HbA1c) change.

Secondary Objectives:

To compare the overall efficacy and safety of the insulin glargine/lixisenatide fixed ratio combination (FRC) to GLP-1 receptor agonist (GLP-1 RA) on top of metformin (with or without pioglitazone, with or without SGLT2 inhibitor) in patients with type 2 diabetes.

To evaluate safety, efficacy and other endpoints of FRC up to the end of the extension period.

Detailed Description

The maximum duration for GLP1-RA patients will be approximately 29 weeks: an up to 2 week screening period, a 26 week treatment period (either randomized or uncontrolled), and a 3 or 9 day post-treatment safety followup period.

Maximum duration for FRC patients will be approximately 55 weeks: an up to 2- week screening period, a 26-week randomized treatment period, a 26-week extension period and a 3-day post-treatment safety follow-up period. All primary and secondary efficacy, safety and other endpoints will be also assessed at the end of the extension period.
Condition or disease Intervention/treatment Phase

Type 2 Diabetes Mellitus

Drug: insulin glargine/lixisenatide fixed ratio combination
Other Names
HOE901/AVE0010
Drug: liraglutide
Other Names
Victoza
Drug: exenatide
Other Names
Byetta
Drug: exenatide extended-release
Other Names
Bydureon
Drug: albiglutide
Other Names
Tanzeum
Drug: dulaglutide
Other Names
Trulicity
Drug: metformin
Other Names
Drug: pioglitazone
Other Names
Drug: SGLT2 inhibitor
Other Names
Phase 3

Tracking Information

First Submitted DateMay 26, 2016
Last Update Posted DateFebruary 22, 2018
Start DateJuly 06, 2016
Anticipated Completion DateNovember 01, 2018
Primary Completion DateMay 24, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change from baseline in HbA1c [Time Frame: Baseline to 26 weeks]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Percentage of participants reaching HbA1c targets [Time Frame: Baseline to 26 weeks]

  • Change from baseline in fasting plasma glucose (FPG) [Time Frame: Baseline to 26 weeks]

  • Change from baseline in 7-point self-monitored plasma glucose (SMPG) profiles [Time Frame: Baseline to 26 weeks]

  • Change from baseline in 2-hour postprandial glucose (PPG) during standardized meal test [Time Frame: Baseline to 26 weeks]

  • Change from baseline in blood glucose excursion during standardized meal test [Time Frame: Baseline to 26 weeks]

  • Change from baseline in body weight [Time Frame: Baseline to 26 weeks]

  • Percentage of participants with symptomatic hypoglycemia [Time Frame: 26 weeks]

  • Number of adverse events [Time Frame: 26 weeks]

  • Percentage of patients requiring rescue therapy [Time Frame: Baseline to 26 weeks]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEfficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Versus GLP-1 Receptor Agonist in Patients With Type 2 Diabetes, With a FRC Extension Period
Official TitleA 26-Week Randomized, Open-label, Active Controlled, Parallel-group, Study Assessing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and Metformin (Alone or With Pioglitazone and/or SGLT2 Inhibitors), Followed by a Fixed Ratio Combination Single-arm 26-Week Extension Period
Brief Summary

Primary Objective:

To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) versus GLP-1 receptor agonist (GLP-1 RA) in hemoglobin A1c (HbA1c) change.

Secondary Objectives:

To compare the overall efficacy and safety of the insulin glargine/lixisenatide fixed ratio combination (FRC) to GLP-1 receptor agonist (GLP-1 RA) on top of metformin (with or without pioglitazone, with or without SGLT2 inhibitor) in patients with type 2 diabetes.

To evaluate safety, efficacy and other endpoints of FRC up to the end of the extension period.

Detailed Description

The maximum duration for GLP1-RA patients will be approximately 29 weeks: an up to 2 week screening period, a 26 week treatment period (either randomized or uncontrolled), and a 3 or 9 day post-treatment safety followup period.

Maximum duration for FRC patients will be approximately 55 weeks: an up to 2- week screening period, a 26-week randomized treatment period, a 26-week extension period and a 3-day post-treatment safety follow-up period. All primary and secondary efficacy, safety and other endpoints will be also assessed at the end of the extension period.

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
500
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Type 2 Diabetes Mellitus
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: insulin glargine/lixisenatide fixed ratio combination

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Other Names
HOE901/AVE0010
Drug: liraglutide

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Other Names
Victoza
Drug: exenatide

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Other Names
Byetta
Drug: exenatide extended-release

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Other Names
Bydureon
Drug: albiglutide

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Other Names
Tanzeum
Drug: dulaglutide

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Other Names
Trulicity
Drug: metformin

Pharmaceutical form: tablet Route of administration: oral

Other Names
Drug: pioglitazone

Pharmaceutical form: tablet Route of administration: oral

Other Names
Drug: SGLT2 inhibitor

Pharmaceutical form: tablet Route of administration: oral

Other Names
Study Groups/Cohorts
Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.

Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.

Study Arms
Experimental Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : insulin glargine/lixisenatide fixed ratio combination
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Experimental Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : metformin
Pharmaceutical form: tablet Route of administration: oral

Experimental Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : pioglitazone
Pharmaceutical form: tablet Route of administration: oral

Experimental Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : SGLT2 inhibitor
Pharmaceutical form: tablet Route of administration: oral

Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : SGLT2 inhibitor
Pharmaceutical form: tablet Route of administration: oral

Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : pioglitazone
Pharmaceutical form: tablet Route of administration: oral

Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : metformin
Pharmaceutical form: tablet Route of administration: oral

Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : liraglutide
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : exenatide
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : exenatide extended-release
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : albiglutide
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : dulaglutide
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Arm Intervention/Treatment
Experimental Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : insulin glargine/lixisenatide fixed ratio combination
Experimental Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : metformin
Experimental Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : pioglitazone
Experimental Insulin glargine/lixisenatide fixed ratio combination
Insulin glargine/lixisenatide fixed ratio combination (FRC) is injected subcutaneously (SC, under the skin) once daily (QD). Dose individually adjusted. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : SGLT2 inhibitor
Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : SGLT2 inhibitor
Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : pioglitazone
Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : metformin
Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : liraglutide
Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : exenatide
Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : exenatide extended-release
Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : albiglutide
Active Comparator Liraglutide/Exenatide/Exenatide ER/Albiglutide/Dulaglutide
Liraglutide will be injected SC (under the skin) QD, and exenatide will be injected SC (under the skin) twice daily (BID). Exenatide extended-release, albiglutide, and dulaglutide are injected SC (under the skin) once weekly. Metformin, pioglitazone (if taken prior to entry in the trial), and SGLT2 inhibitor (if taken prior to entry in the trial) treatments should be continued.
Drug : dulaglutide

Recruitment Information

Recruitment Status:Recruiting
Enrollment500
Completion DateNovember 01, 2018
Eligibility Criteria: Inclusion criteria :
- Patients with type 2 diabetes mellitus diagnosed at least 1 year prior to screening visit.
- Patients who have been treated with one of the following glucagon-like peptide 1 (GLP-1) receptor agonists for at least 4 months prior to screening visit (V1), and with stable dose for at least 3 months prior to screening visit (V1):
- Liraglutide (Victoza®) 1.8 mg QD or 1.2 mg QD, if the 1.8 mg QD dose is not well tolerated according to the Investigator's judgment or
- Exenatide (Byetta®) 10 µg BID or of 5 µg BID, if 10 µg BID dose is not well tolerated according to the Investigator's judgment in combination with metformin (daily dose ≥1500 mg/day or maximum tolerated dose [MTD]), with or without pioglitazone, with or without SGLT2 inhibitor, all at stable dose for at least 3 months prior to screening.
or
Patients who have been treated with stable dose of one of the following GLP-1 receptor agonists for at least 6 months prior to screening visit (V1):
- Exenatide extended-release (Bydureon®) 2 mg once weekly (QW), if well tolerated according to Investigator's judgment,
- Albiglutide (Tanzeum®) 50 mg QW or 30 mg QW, if 50 mg QW is not well tolerated according to Investigator's judgment,
- Dulaglutide (Trulicity®) 1.5 mg QW or 0.75 mg QW, if 1.5 mg QW is not well tolerated according to Investigator's judgment in combination with metformin (daily dose ≥1500 mg/day or MTD), with or without pioglitazone, with or without SGLT2 inhibitor, all at stable dose for at least 3 months prior to screening;
- Signed written informed consent.
Exclusion criteria:
- At screening visit, age <18.
- Screening HbA1c <7% and >9%.
- Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
- Any use of antidiabetic drugs within 3 months prior to the screening visit other than those described in the inclusion criteria.
- Previous treatment with insulin in the year prior to screening visit (note: short-term treatment with insulin [≤10 days] due to intercurrent illness including gestational diabetes is allowed at the discretion of the study physician).
- Laboratory findings at the time of screening, including:
- Fasting plasma glucose (FPG) >250 mg/dL (13.9 mmol/L),
- Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN),
- Alanine transaminase or aspartate transaminase >3 ULN,
- Calcitonin ≥20 pg/mL (5.9 pmol/L),
- Positive pregnancy test.
- Patient who has renal function impairment with estimated glomerular filtration rate <30mL/min/1.73m2 (using the Modification of Diet in Renal Disease formula) or end-stage renal disease.
- Contraindication to use of insulin glargine, or lixisenatide or GLP-1 receptor agonist (Victoza®, Byetta®, Bydureon®, Tanzeum® or Trulicity®) according to local labeling.
- Any contraindication to metformin or pioglitazone or SGLT2 inhibitor use, according to local labeling.
- History of hypersensitivity to insulin glargine, or to any of the excipients.
- History of allergic reaction to any GLP-1 receptor agonist or to meta-cresol.
- Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia type 2 syndromes).
- History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy.
- Body mass index ≤20 or >40 kg/m^2.
Exclusion criteria for the extension period:
- Patients in the FRC arm with a rescue therapy and HbA1c >8% at week 22.
- Patients in the FRC arm who discontinued prematurely from FRC treatment before week 26.
- Patients in the GLP-1 RA treatment arm after randomization.
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
Listed Location Countries
Canada
Estonia
Germany
Israel
Italy
Romania
Slovakia
Spain
United States

Administrative Information

NCT Number:NCT02787551
Other Study ID Numbers
EFC13794
2014-004850-32
U1111-1168-4639
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