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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 (LixiLan-G)

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Sanofi

Status and phase

Completed
Phase 3

Conditions

Type 2 Diabetes Mellitus

Treatments

Drug: liraglutide
Drug: dulaglutide
Drug: Insulin glargine/lixisenatide fixed ratio combination
Drug: albiglutide
Drug: Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)
Drug: exenatide
Drug: exenatide extended-release

Study type

Interventional

Funder types

Industry

Identifiers

NCT02787551
EFC13794
U1111-1168-4639 (Other Identifier)
2014-004850-32

Details and patient eligibility

About

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 FRC to GLP-1 RA on top of metformin (with or without pioglitazone, with or without sodium-glucose co-transporter 2 [SGLT2] inhibitor) in participants with type 2 diabetes.

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

Full description

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

Maximum duration for FRC participants was approximately 55 weeks: 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 outcome measures were assessed at the end of the extension period.

Enrollment

514 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

  • Participants with type 2 diabetes mellitus diagnosed at least 1 year prior to screening visit.
  • Participants who were treated with one of the following GLP-1 receptor agonists for at least 4 months prior to screening visit 1 (V1), and with stable dose for at least 3 months prior to screening visit (V1):
  • Liraglutide (Victoza®) 1.8 milligram (mg) QD or 1.2 mg QD, if the 1.8 mg QD dose was not well tolerated according to the Investigator's judgment or
  • Exenatide (Byetta®) 10 microgram (µg) BID or of 5 µg BID, if 10 µg BID dose was not well tolerated according to the Investigator's judgment

in combination with metformin (daily dose greater than equal to [>=] 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

Participants who were 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 was not well tolerated according to Investigator's judgment,
  • Dulaglutide (Trulicity®) 1.5 mg QW or 0.75 mg QW, if 1.5 mg QW was 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 was 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 millimoles per litre [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.
  • Participant who had renal function impairment with estimated glomerular filtration rate <30mL/min/1.73m^2 (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:

  • Participants in the FRC arm with a rescue therapy and HbA1c >8% at week 22.
  • Participants in the FRC arm who discontinued prematurely from FRC treatment before week 26.
  • Participants 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

514 participants in 2 patient groups

Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)
Experimental group
Description:
Core period: FRC injected subcutaneously once daily (QD) for 26 weeks on top of oral anti-diabetic drug (OAD) therapy. Dose individually adjusted. Single arm extension period: Participants who completed core treatment period and met eligibility criteria entered in extension treatment period and received same treatment (FRC injected subcutaneously QD on top of OAD therapy) for 26 weeks (up to Week 52). Dose individually adjusted.
Treatment:
Drug: Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)
Drug: Insulin glargine/lixisenatide fixed ratio combination
GLP-1 Receptor Agonist
Active Comparator group
Description:
Core period: GLP-1 RA receptor agonist (liraglutide QD, exenatide twice daily \[BID\], exenatide extended-release QW, albiglutide QW, or dulaglutide QW) injected subcutaneously for 26 weeks on top of OAD therapy. GLP-1 RAs were administered as per local labeling at the same dose schedule as prior to randomization.
Treatment:
Drug: exenatide extended-release
Drug: Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)
Drug: exenatide
Drug: albiglutide
Drug: dulaglutide
Drug: liraglutide

Trial documents
2

Trial contacts and locations

124

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Data sourced from clinicaltrials.gov

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