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

NCT ID: NCT02787551

Last Updated: 2022-03-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

514 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-06

Study Completion Date

2018-11-17

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)

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.

Group Type EXPERIMENTAL

Insulin glargine/lixisenatide fixed ratio combination

Intervention Type DRUG

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)

Intervention Type DRUG

Pharmaceutical form: tablet Route of administration: oral If previously taken, doses to remain stable through the study.

GLP-1 Receptor Agonist

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.

Group Type ACTIVE_COMPARATOR

liraglutide

Intervention Type DRUG

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

exenatide

Intervention Type DRUG

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

exenatide extended-release

Intervention Type DRUG

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

albiglutide

Intervention Type DRUG

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

dulaglutide

Intervention Type DRUG

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)

Intervention Type DRUG

Pharmaceutical form: tablet Route of administration: oral If previously taken, doses to remain stable through the study.

Interventions

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Insulin glargine/lixisenatide fixed ratio combination

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Intervention Type DRUG

liraglutide

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Intervention Type DRUG

exenatide

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Intervention Type DRUG

exenatide extended-release

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Intervention Type DRUG

albiglutide

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Intervention Type DRUG

dulaglutide

Pharmaceutical form: solution for injection

Route of administration: subcutaneous

Intervention Type DRUG

Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)

Pharmaceutical form: tablet Route of administration: oral If previously taken, doses to remain stable through the study.

Intervention Type DRUG

Other Intervention Names

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HOE901/AVE0010 Soliqua Victoza Byetta Bydureon Tanzeum Trulicity

Eligibility Criteria

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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.

* 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

* At screening visit, age \<18.
* Screening HbA1c \<7% and \>9%.
* Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 8400064

Birmingham, Alabama, United States

Site Status

Investigational Site Number 8400073

Fountain Hills, Arizona, United States

Site Status

Investigational Site Number 8400047

Phoenix, Arizona, United States

Site Status

Investigational Site Number 8400103

Bakersfield, California, United States

Site Status

Investigational Site Number 8400137

Fresno, California, United States

Site Status

Investigational Site Number 8400043

Huntington Park, California, United States

Site Status

Investigational Site Number 8400124

Lamont, California, United States

Site Status

Investigational Site Number 8400027

Lancaster, California, United States

Site Status

Investigational Site Number 8400098

Los Angeles, California, United States

Site Status

Investigational Site Number 8400013

Los Angeles, California, United States

Site Status

Investigational Site Number 8400042

Mission Hills, California, United States

Site Status

Investigational Site Number 8400006

Northridge, California, United States

Site Status

Investigational Site Number 8400021

Orange, California, United States

Site Status

Investigational Site Number 8400126

Rialto, California, United States

Site Status

Investigational Site Number 8400094

Santa Ana, California, United States

Site Status

Investigational Site Number 8400009

Ventura, California, United States

Site Status

Investigational Site Number 8400071

Denver, Colorado, United States

Site Status

Investigational Site Number 8400036

Denver, Colorado, United States

Site Status

Investigational Site Number 8400114

Jacksonville, Florida, United States

Site Status

Investigational Site Number 8400133

Miami, Florida, United States

Site Status

Investigational Site Number 8400058

Port Charlotte, Florida, United States

Site Status

Investigational Site Number 8400084

Tampa, Florida, United States

Site Status

Investigational Site Number 8400112

West Palm Beach, Florida, United States

Site Status

Investigational Site Number 8400045

Lawrenceville, Georgia, United States

Site Status

Investigational Site Number 8400096

Snellville, Georgia, United States

Site Status

Investigational Site Number 8400023

Springfield, Illinois, United States

Site Status

Investigational Site Number 8400049

Avon, Indiana, United States

Site Status

Investigational Site Number 8400053

Avon, Indiana, United States

Site Status

Investigational Site Number 8400085

Avon, Indiana, United States

Site Status

Investigational Site Number 8400120

Avon, Indiana, United States

Site Status

Investigational Site Number 8400041

Evansville, Indiana, United States

Site Status

Investigational Site Number 8400038

Indianapolis, Indiana, United States

Site Status

Investigational Site Number 8400130

Council Bluffs, Iowa, United States

Site Status

Investigational Site Number 8400034

Lexington, Kentucky, United States

Site Status

Investigational Site Number 8400091

Lexington, Kentucky, United States

Site Status

Investigational Site Number 8400078

Marrero, Louisiana, United States

Site Status

Investigational Site Number 8400032

Metairie, Louisiana, United States

Site Status

Investigational Site Number 8400088

New Orleans, Louisiana, United States

Site Status

Investigational Site Number 8400033

Baltimore, Maryland, United States

Site Status

Investigational Site Number 8400051

Jefferson City, Missouri, United States

Site Status

Investigational Site Number 8400083

Papillion, Nebraska, United States

Site Status

Investigational Site Number 8400044

Henderson, Nevada, United States

Site Status

Investigational Site Number 8400079

Albany, New York, United States

Site Status

Investigational Site Number 8400061

New York, New York, United States

Site Status

Investigational Site Number 8400123

North Massapequa, New York, United States

Site Status

Investigational Site Number 8400095

Staten Island, New York, United States

Site Status

Investigational Site Number 8400067

West Seneca, New York, United States

Site Status

Investigational Site Number 8400111

Yonkers, New York, United States

Site Status

Investigational Site Number 8400020

Morehead City, North Carolina, United States

Site Status

Investigational Site Number 8400065

Wilmington, North Carolina, United States

Site Status

Investigational Site Number 8400018

Fargo, North Dakota, United States

Site Status

Investigational Site Number 8400019

Columbus, Ohio, United States

Site Status

Investigational Site Number 8400056

Dayton, Ohio, United States

Site Status

Investigational Site Number 8400125

Mentor, Ohio, United States

Site Status

Investigational Site Number 8400099

Oklahoma City, Oklahoma, United States

Site Status

Investigational Site Number 8400129

Scottdale, Pennsylvania, United States

Site Status

Investigational Site Number 8400076

Smithfield, Pennsylvania, United States

Site Status

Investigational Site Number 8400104

Warwick, Rhode Island, United States

Site Status

Investigational Site Number 8400090

Columbia, South Carolina, United States

Site Status

Investigational Site Number 8400139

Austin, Texas, United States

Site Status

Investigational Site Number 8400001

Dallas, Texas, United States

Site Status

Investigational Site Number 8400118

Edinburg, Texas, United States

Site Status

Investigational Site Number 8400008

Houston, Texas, United States

Site Status

Investigational Site Number 8400109

Houston, Texas, United States

Site Status

Investigational Site Number 8400063

Houston, Texas, United States

Site Status

Investigational Site Number 8400106

Houston, Texas, United States

Site Status

Investigational Site Number 8400014

North Richland Hills, Texas, United States

Site Status

Investigational Site Number 8400089

San Antonio, Texas, United States

Site Status

Investigational Site Number 8400135

Schertz, Texas, United States

Site Status

Investigational Site Number 8400075

Shavano Park, Texas, United States

Site Status

Investigational Site Number 8400107

Sugar Land, Texas, United States

Site Status

Investigational Site Number 8400054

Orem, Utah, United States

Site Status

Investigational Site Number 8400025

Salt Lake City, Utah, United States

Site Status

Investigational Site Number 8400092

Weber City, Virginia, United States

Site Status

Investigational Site Number 1240003

Burlington, , Canada

Site Status

Investigational Site Number 1240006

Corunna, , Canada

Site Status

Investigational Site Number 1240002

Red Deer, , Canada

Site Status

Investigational Site Number 1240001

Vancouver, , Canada

Site Status

Investigational Site Number 2330002

Pärnu, , Estonia

Site Status

Investigational Site Number 2330003

Tallinn, , Estonia

Site Status

Investigational Site Number 2330001

Tallinn, , Estonia

Site Status

Investigational Site Number 2330004

Viljandi, , Estonia

Site Status

Investigational Site Number 2760001

Dresden, , Germany

Site Status

Investigational Site Number 2760003

Oldenburg in Holstein, , Germany

Site Status

Investigational Site Number 3760001

Haifa, , Israel

Site Status

Investigational Site Number 3760002

Haifa, , Israel

Site Status

Investigational Site Number 3760005

Jerusalem, , Israel

Site Status

Investigational Site Number 3760006

Jerusalem, , Israel

Site Status

Investigational Site Number 3760004

Tel Aviv, , Israel

Site Status

Investigational Site Number 3800008

Bergamo, , Italy

Site Status

Investigational Site Number 3800002

Bologna, , Italy

Site Status

Investigational Site Number 3800001

Milan, , Italy

Site Status

Investigational Site Number 3800006

Milan, , Italy

Site Status

Investigational Site Number 3800005

Napoli, , Italy

Site Status

Investigational Site Number 3800004

Roma, , Italy

Site Status

Investigational Site Number 3800003

Roma, , Italy

Site Status

Investigational Site Number 6420004

Bacau, , Romania

Site Status

Investigational Site Number 6420006

Brasov, , Romania

Site Status

Investigational Site Number 6420001

Bucharest, , Romania

Site Status

Investigational Site Number 6420008

Buzău, , Romania

Site Status

Investigational Site Number 6420003

Cluj-Napoca, , Romania

Site Status

Investigational Site Number 6420002

Oradea, , Romania

Site Status

Investigational Site Number 6420009

Târgovişte, , Romania

Site Status

Investigational Site Number 6420007

Târgu Mureş, , Romania

Site Status

Investigational Site Number 6420005

Timișoara, , Romania

Site Status

Investigational Site Number 7030006

Bratislava, , Slovakia

Site Status

Investigational Site Number 7030002

Lučenec, , Slovakia

Site Status

Investigational Site Number 7030009

Ľubochňa, , Slovakia

Site Status

Investigational Site Number 7030005

Malacky, , Slovakia

Site Status

Investigational Site Number 7030007

Prešov, , Slovakia

Site Status

Investigational Site Number 7030001

Rožňava, , Slovakia

Site Status

Investigational Site Number 7030008

Sabinov, , Slovakia

Site Status

Investigational Site Number 7030004

Trenčín, , Slovakia

Site Status

Investigational Site Number 7030003

Žilina, , Slovakia

Site Status

Investigational Site Number 7240012

Alzira, , Spain

Site Status

Investigational Site Number 7240005

Barcelona, , Spain

Site Status

Investigational Site Number 7240002

Ferrol, , Spain

Site Status

Investigational Site Number 7240008

Málaga, , Spain

Site Status

Investigational Site Number 7240011

Pozuelo de Alarcón, , Spain

Site Status

Investigational Site Number 7240003

Quart de Poblet, , Spain

Site Status

Investigational Site Number 7240006

Sabadell, , Spain

Site Status

Investigational Site Number 7240007

Seville, , Spain

Site Status

Investigational Site Number 7240009

Seville, , Spain

Site Status

Investigational Site Number 7240004

Seville, , Spain

Site Status

Countries

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United States Canada Estonia Germany Israel Italy Romania Slovakia Spain

References

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Kuruvilla DE, Mann JI, Tepper SJ, Starling AJ, Panza G, Johnson MAL. Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM). Sci Rep. 2022 Mar 24;12(1):5110. doi: 10.1038/s41598-022-09071-6.

Reference Type DERIVED
PMID: 35332216 (View on PubMed)

Ferrannini E, Niemoeller E, Dex T, Servera S, Mari A. Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ss-cell function in people with type 2 diabetes. Diabetes Obes Metab. 2022 Jun;24(6):1159-1165. doi: 10.1111/dom.14688. Epub 2022 Mar 28.

Reference Type DERIVED
PMID: 35257461 (View on PubMed)

Guja C, Giorgino F, Blonde L, Ali A, Prazny M, Meier JJ, Souhami E, Lubwama R, Ji C, Rosenstock J. Concomitant iGlarLixi and Sodium-Glucose Co-transporter-2 Inhibitor Therapy in Adults with Type 2 Diabetes: LixiLan-G Trial and Real-World Evidence Results. Diabetes Ther. 2022 Jan;13(1):205-215. doi: 10.1007/s13300-021-01180-1. Epub 2021 Dec 11.

Reference Type DERIVED
PMID: 34894329 (View on PubMed)

Blonde L, Rosenstock J, Frias J, Birkenfeld AL, Niemoeller E, Souhami E, Ji C, Del Prato S, Aroda VR. Durable Effects of iGlarLixi Up to 52 Weeks in Type 2 Diabetes: The LixiLan-G Extension Study. Diabetes Care. 2021 Mar;44(3):774-780. doi: 10.2337/dc20-2023. Epub 2021 Jan 19.

Reference Type DERIVED
PMID: 33468520 (View on PubMed)

Blonde L, Rosenstock J, Del Prato S, Henry R, Shehadeh N, Frias J, Niemoeller E, Souhami E, Ji C, Aroda VR. Switching to iGlarLixi Versus Continuing Daily or Weekly GLP-1 RA in Type 2 Diabetes Inadequately Controlled by GLP-1 RA and Oral Antihyperglycemic Therapy: The LixiLan-G Randomized Clinical Trial. Diabetes Care. 2019 Nov;42(11):2108-2116. doi: 10.2337/dc19-1357. Epub 2019 Sep 17.

Reference Type DERIVED
PMID: 31530665 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014-004850-32

Identifier Type: -

Identifier Source: secondary_id

U1111-1168-4639

Identifier Type: OTHER

Identifier Source: secondary_id

EFC13794

Identifier Type: -

Identifier Source: org_study_id

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