Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— LixiLan-L  

Official title:

A Randomized, 30-week, Active-controlled, Open Label, 2- Treatment Arm, Parallel-group, Multicenter Study Comparing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine With or Without Metformin in Patients With Type 2 Diabetes Mellitus (T2DM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02058160
• Other study ID #: EFC12405
• Secondary ID: 2013-003132-79U1
• Status: Completed
• Phase: Phase 3
• First received: February 6, 2014
• Last updated: July 1, 2016
• Start date: January 2014
• Est. completion date: July 2015

Study information

• Verified date: July 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination to insulin glargine in HbA1c change from baseline to week 30.

Secondary Objective:

To compare the overall efficacy and safety of insulin glargine/lixisenatide fixed ratio combination to insulin glargine (with or without metformin) over a 30 week treatment period in patients with type 2 diabetes

Description:

Maximum duration of approximately 39 weeks: an up to 8-week screening period, a 30-week randomized treatment period and 3 days post-treatment safety follow up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 736
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Type 2 diabetes mellitus diagnosed at least 1 year before the screening visit.

• Treatment with basal insulin for at least 6 months before the screening visit.

• Stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection) for at least 3 months before the screening visit.

• Stable (plus/minus 20 percent) total daily basal insulin dose between 15 and 40 Units/day for at least 2 months prior to the screening visit.

• For patients receiving basal insulin AND 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months before the screening visit. The OADs can be 1 to 2 out of:

• metformin (more than or equal to1500mg/day or maximal tolerated dose),

• a sulfonylurea

• a glinide,

• a dipeptidyl-peptidase-4 inhibitor

• a sodium glucose co-transporter 2 inhibitor

• Fasting plasma glucose (FPG) less than or equal to 180 mg/dL(10.0 mmol/L) at screening visit for patients receiving basal insulin in combination with 2 OADs or with 1 OAD other than metformin; FPG less than or equal to 200 mg/dL (11.1 mmol/L) at screening visit for patients on basal insulin only or basal insulin plus metformin at screening visit,

• Signed written informed consent.

Exclusion criteria:

• Age under legal age of adulthood at screening visit

• HbA1c at screening visit less than 7.5% or above 10%.

• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.

• Use of other oral or injectable glucose-lowering agents than stated in the inclusion criteria in a period of 3 months prior to screening.

• Previous use of insulin other than basal insulin eg, prandial or pre-mixed insulin, in the year prior to screening. Note: Short term treatment (=10 days) due to intercurrent illness is allowed.

• History discontinuation of a previous treatment with Glucagon Like Peptide -1 Receptor Agonists for safety/tolerability or lack of efficacy.

• Patient who has previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide fixed ratio combination or has previously received lixisenatide.

• Use of weight loss drugs within 3 months prior to screening visit.

• Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.

• 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, stomach/gastric surgery.

• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).

• Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit

• At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m²

• At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range,

• At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 3 ULN

• At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L)

• Any contraindication to metformin use, according to local labeling, if the patient is taking metformin.

• Patient who has a renal function impairment with creatinine clearance less than 30 mL/min (using the Cockcroft and Gault formula) or end-stage renal disease for patients, not treated with metformin.

Exclusion criteria for randomization:

• HbA1c less than 7% or above 10% .

• Mean fasting Self Measured Plasma Glucose (SMPG) calculated from the self-measurements for 7 days the week before randomization visit is above 140 mg/dL (7.8 mmol/L).

• Average insulin glargine daily dose less than 20 Units or above 50 Units ( in the week before randomization visit).

• Amylase and/or lipase more than 3 ULN .

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Insulin glargine/lixisenatide (HOE901/AVE0010)
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
• Insulin glargine (HOE901)
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
• Metformin
Pharmaceutical form:tablet Route of administration: oral administration

Locations

Country	Name	City	State
Australia	Investigational Site Number 036505	Box Hill
Australia	Investigational Site Number 036501	Heidelberg
Australia	Investigational Site Number 036504	Parkville
Canada	Investigational Site Number 124504	Beamsville
Canada	Investigational Site Number 124512	Brampton
Canada	Investigational Site Number 124502	Guelph
Canada	Investigational Site Number 124507	Kelowna
Canada	Investigational Site Number 124505	Montreal
Canada	Investigational Site Number 124511	Oakville
Canada	Investigational Site Number 124509	St-Romuald
Canada	Investigational Site Number 124503	Toronto
Canada	Investigational Site Number 124510	Toronto
Canada	Investigational Site Number 124501	Vancouver
Canada	Investigational Site Number 124508	Victoria
Chile	Investigational Site Number 152511	Puerto Varas
Chile	Investigational Site Number 152501	Santiago
Chile	Investigational Site Number 152502	Santiago
Chile	Investigational Site Number 152503	Santiago
Chile	Investigational Site Number 152507	Santiago
Chile	Investigational Site Number 152514	Santiago
Chile	Investigational Site Number 152509	Talagante
Chile	Investigational Site Number 152513	Temuco
Chile	Investigational Site Number 152504	Vina Del Mar
Czech Republic	Investigational Site Number 203502	Cheb
Czech Republic	Investigational Site Number 203504	Hranice
Czech Republic	Investigational Site Number 203507	Krnov
Czech Republic	Investigational Site Number 203506	Liberec
Czech Republic	Investigational Site Number 203503	Olomouc
Czech Republic	Investigational Site Number 203514	Plzen
Czech Republic	Investigational Site Number 203515	Plzen
Czech Republic	Investigational Site Number 203511	Praha 4
Czech Republic	Investigational Site Number 203508	Praha 5
Czech Republic	Investigational Site Number 203509	Praha 8
Czech Republic	Investigational Site Number 203505	Prostejov
Denmark	Investigational Site Number 208503	Aarhus C
Denmark	Investigational Site Number 208509	Horsens
Denmark	Investigational Site Number 208501	København Nv
Denmark	Investigational Site Number 208505	København S
Denmark	Investigational Site Number 208502	Kolding
Denmark	Investigational Site Number 208504	Viborg
Estonia	Investigational Site Number 233502	Pärnu
Estonia	Investigational Site Number 233503	Tallinn
Estonia	Investigational Site Number 233501	Tartu
Hungary	Investigational Site Number 348501	Budapest
Hungary	Investigational Site Number 348503	Budapest
Hungary	Investigational Site Number 348505	Budapest
Hungary	Investigational Site Number 348502	Debrecen
Hungary	Investigational Site Number 348506	Kaposvár
Hungary	Investigational Site Number 348504	Pápa
Lithuania	Investigational Site Number 440501	Kaunas
Lithuania	Investigational Site Number 440503	Kaunas
Lithuania	Investigational Site Number 440505	Kedainiai
Lithuania	Investigational Site Number 440504	Klaipeda
Lithuania	Investigational Site Number 440502	Vilnius
Mexico	Investigational Site Number 484508	Celaya
Mexico	Investigational Site Number 484501	Cuernavaca
Mexico	Investigational Site Number 484503	Guadalajara
Mexico	Investigational Site Number 484504	Guadalajara
Mexico	Investigational Site Number 484506	Guadalajara
Mexico	Investigational Site Number 484509	México
Mexico	Investigational Site Number 484507	Pachuca
Mexico	Investigational Site Number 484505	Puebla
Netherlands	Investigational Site Number 528505	Almere
Poland	Investigational Site Number 616502	Bialystok
Poland	Investigational Site Number 616505	Krakow
Poland	Investigational Site Number 616506	Krakow
Poland	Investigational Site Number 616507	Plock
Poland	Investigational Site Number 616504	Szczecin
Poland	Investigational Site Number 616501	Warszawa
Poland	Investigational Site Number 616503	Warszawa
Romania	Investigational Site Number 642507	Brasov
Romania	Investigational Site Number 642510	Bucharest
Romania	Investigational Site Number 642508	Bucuresti
Romania	Investigational Site Number 642509	Bucuresti
Romania	Investigational Site Number 642506	Hunedoara
Romania	Investigational Site Number 642505	Iasi
Romania	Investigational Site Number 642502	Oradea
Romania	Investigational Site Number 642511	Sibiu
Romania	Investigational Site Number 642501	Targu Mures
Romania	Investigational Site Number 642503	Timisoara
Romania	Investigational Site Number 642504	Timisoara
Russian Federation	Investigational Site Number 643511	Arkhangelsk
Russian Federation	Investigational Site Number 643512	Moscow
Russian Federation	Investigational Site Number 643508	Penza
Russian Federation	Investigational Site Number 643501	Saint-Petersburg
Russian Federation	Investigational Site Number 643513	Samara
Russian Federation	Investigational Site Number 643507	Saratov
Russian Federation	Investigational Site Number 643514	Saratov
Russian Federation	Investigational Site Number 643502	St-Petersburg
Russian Federation	Investigational Site Number 643503	St-Petersburg
Russian Federation	Investigational Site Number 643504	St-Petersburg
Russian Federation	Investigational Site Number 643506	St-Petersburg
Russian Federation	Investigational Site Number 643505	St. Petersburg
Russian Federation	Investigational Site Number 643509	Voronezh
Slovakia	Investigational Site Number 703505	Bratislava
Slovakia	Investigational Site Number 703507	Bytca
Slovakia	Investigational Site Number 703502	Kosice
Slovakia	Investigational Site Number 703510	Kosice
Slovakia	Investigational Site Number 703512	Kosice
Slovakia	Investigational Site Number 703511	Lubochna
Slovakia	Investigational Site Number 703508	Moldava Nad Bodvou
Slovakia	Investigational Site Number 703504	Nove Mesto Nad Vahom
Slovakia	Investigational Site Number 703509	Nove Zamky
Slovakia	Investigational Site Number 703513	Trnava
Slovakia	Investigational Site Number 703501	Zilina
Spain	Investigational Site Number 724509	Alicante
Spain	Investigational Site Number 724506	Alzira
Spain	Investigational Site Number 724504	Barcelona
Spain	Investigational Site Number 724510	Barcelona
Spain	Investigational Site Number 724505	Cáceres
Spain	Investigational Site Number 724503	El Ferrol
Spain	Investigational Site Number 724508	La Coruña
Spain	Investigational Site Number 724501	Sabadell
Spain	Investigational Site Number 724507	Segovia
Spain	Investigational Site Number 724502	Valencia
Sweden	Investigational Site Number 752501	Ljungby
Sweden	Investigational Site Number 752503	Malmö
Sweden	Investigational Site Number 752504	Rättvik
Sweden	Investigational Site Number 752506	Stenungssund
Sweden	Investigational Site Number 752505	Stockholm
Sweden	Investigational Site Number 752502	Vällingby
Ukraine	Investigational Site Number 804501	Chernivtsi
Ukraine	Investigational Site Number 804507	Kyiv
Ukraine	Investigational Site Number 804510	Kyiv
Ukraine	Investigational Site Number 804511	Kyiv
Ukraine	Investigational Site Number 804513	Lviv
Ukraine	Investigational Site Number 804502	Vinnytsya
Ukraine	Investigational Site Number 804508	Vinnytsya
United States	Investigational Site Number 840576	Albuquerque	New Mexico
United States	Investigational Site Number 840605	Amarillo	Texas
United States	Investigational Site Number 840580	Arlington Heights	Illinois
United States	Investigational Site Number 840594	Atlanta	Georgia
United States	Investigational Site Number 840582	Aurora	Colorado
United States	Investigational Site Number 840553	Austin	Texas
United States	Investigational Site Number 840598	Austin	Texas
United States	Investigational Site Number 840543	Avon	Indiana
United States	Investigational Site Number 840520	Baltimore	Maryland
United States	Investigational Site Number 840560	Baltimore	Maryland
United States	Investigational Site Number 840568	Bell Gardens	California
United States	Investigational Site Number 840607	Birmingham	Alabama
United States	Investigational Site Number 840613	Burlington	Vermont
United States	Investigational Site Number 840558	Butte	Montana
United States	Investigational Site Number 840622	Charleston	South Carolina
United States	Investigational Site Number 840504	Chesapeake	Virginia
United States	Investigational Site Number 840519	Chicago	Illinois
United States	Investigational Site Number 840612	Chicago	Illinois
United States	Investigational Site Number 840550	Chino	California
United States	Investigational Site Number 840529	Chula Vista	California
United States	Investigational Site Number 840579	Columbus	Ohio
United States	Investigational Site Number 840614	Columbus	Georgia
United States	Investigational Site Number 840623	Corona	California
United States	Investigational Site Number 840502	Corpus Christi	Texas
United States	Investigational Site Number 840530	Dallas	Texas
United States	Investigational Site Number 840545	Dallas	Texas
United States	Investigational Site Number 840547	Dallas	Texas
United States	Investigational Site Number 840586	Dallas	Texas
United States	Investigational Site Number 840601	Dallas	Texas
United States	Investigational Site Number 840524	Dayton	Ohio
United States	Investigational Site Number 840505	Dearborn	Michigan
United States	Investigational Site Number 840509	Denver	Colorado
United States	Investigational Site Number 840512	Draper	Utah
United States	Investigational Site Number 840541	Durham	North Carolina
United States	Investigational Site Number 840554	Edinburg	Texas
United States	Investigational Site Number 840618	Eugene	Oregon
United States	Investigational Site Number 840565	Evansville	Indiana
United States	Investigational Site Number 840585	Evansville	Indiana
United States	Investigational Site Number 840615	Evansville	Indiana
United States	Investigational Site Number 840571	Federal Way	Washington
United States	Investigational Site Number 840575	Flint	Michigan
United States	Investigational Site Number 840566	Fresno	California
United States	Investigational Site Number 840552	Greenbrae	California
United States	Investigational Site Number 840604	Greenville	North Carolina
United States	Investigational Site Number 840600	Henderson	Nevada
United States	Investigational Site Number 840540	Hickory	North Carolina
United States	Investigational Site Number 840544	Houston	Texas
United States	Investigational Site Number 840514	Hurst	Texas
United States	Investigational Site Number 840588	Idaho Falls	Idaho
United States	Investigational Site Number 840507	Indianapolis	Indiana
United States	Investigational Site Number 840563	Indianapolis	Indiana
United States	Investigational Site Number 840583	Jamaica	New York
United States	Investigational Site Number 840578	Lancaster	California
United States	Investigational Site Number 840532	Las Vegas	Nevada
United States	Investigational Site Number 840599	Las Vegas	Nevada
United States	Investigational Site Number 840501	Lawrenceville	Georgia
United States	Investigational Site Number 840595	Lewiston	Maine
United States	Investigational Site Number 840517	Little Rock	Arkansas
United States	Investigational Site Number 840537	Little Rock	Arkansas
United States	Investigational Site Number 840581	Los Angeles	California
United States	Investigational Site Number 840626	Los Angeles	California
United States	Investigational Site Number 840516	Louisville	Kentucky
United States	Investigational Site Number 840503	Maumee	Ohio
United States	Investigational Site Number 840510	Miami	Florida
United States	Investigational Site Number 840546	Milwaukee	Wisconsin
United States	Investigational Site Number 840564	Minneapolis	Minnesota
United States	Investigational Site Number 840621	Mission Viejo	California
United States	Investigational Site Number 840513	Morehead City	North Carolina
United States	Investigational Site Number 840591	Murray	Utah
United States	Investigational Site Number 840617	N Richland Hill	Texas
United States	Investigational Site Number 840539	Nashua	New Hampshire
United States	Investigational Site Number 840531	New Hyde Park	New York
United States	Investigational Site Number 840521	New Port Richey	Florida
United States	Investigational Site Number 840561	Norfolk	Virginia
United States	Investigational Site Number 840625	Norfolk	Virginia
United States	Investigational Site Number 840511	Northridge	California
United States	Investigational Site Number 840602	Ocala	Florida
United States	Investigational Site Number 840538	Ocoee	Florida
United States	Investigational Site Number 840526	Ogden	Utah
United States	Investigational Site Number 840506	Omaha	Nebraska
United States	Investigational Site Number 840597	Orem	Utah
United States	Investigational Site Number 840534	Palm Harbor	Florida
United States	Investigational Site Number 840573	Palm Springs	California
United States	Investigational Site Number 840610	Philadelphia	Pennsylvania
United States	Investigational Site Number 840559	Port Hueneme	California
United States	Investigational Site Number 840611	Rapid City	South Dakota
United States	Investigational Site Number 840606	Richmond	Virginia
United States	Investigational Site Number 840522	Rockville	Maryland
United States	Investigational Site Number 840525	Roswell	Georgia
United States	Investigational Site Number 840608	Salem	Virginia
United States	Investigational Site Number 840592	Salisbury	North Carolina
United States	Investigational Site Number 840590	Salt Lake City	Utah
United States	Investigational Site Number 840536	San Ramon	California
United States	Investigational Site Number 840567	Santa Ana	California
United States	Investigational Site Number 840551	Smithfield	Pennsylvania
United States	Investigational Site Number 840593	Spokane	Washington
United States	Investigational Site Number 840556	Springfield	Illinois
United States	Investigational Site Number 840570	Sun City	Arizona
United States	Investigational Site Number 840557	Syracuse	New York
United States	Investigational Site Number 840609	Tacoma	Washington
United States	Investigational Site Number 840569	Tarzana	California
United States	Investigational Site Number 840562	Tempe	Arizona
United States	Investigational Site Number 840584	Tipton	Pennsylvania
United States	Investigational Site Number 840577	Tucson	Arizona
United States	Investigational Site Number 840572	West Hills	California
United States	Investigational Site Number 840535	Wilmington	North Carolina
United States	Investigational Site Number 840549	Wilmington	Delaware
United States	Investigational Site Number 840515	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  Czech Republic,  Denmark,  Estonia,  Hungary,  Lithuania,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c from baseline		week 30	No
Secondary	Percentage of patients reaching HbA1c targets		week 30	No
Secondary	Change in 2-hour Post Prandial Glucose and in blood glucose excursion during standardized meal test from baseline to week 30		week 30	No
Secondary	Change in body weight from baseline		week 30	No
Secondary	Change in 7-point Self-Monitoring Plasma Glucose profiles from baseline		week 30	No
Secondary	Change in daily dose of insulin glargine from baseline		week 30	No
Secondary	Change in Fasting Plasma Glucose from baseline		week 30	No
Secondary	Documented (plasma glucose less than or equal to 70 mg/dl) symptomatic hypoglycemia		30 weeks	Yes
Secondary	Severe symptomatic hypoglycemia		30 weeks	Yes