Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM

Type 2 Diabetes Clinical Trial

— LixiLan-O  

Official title:

A Randomized, 30 Week, Active-controlled, Open-label, 3-treatment Arm, Parallel-group Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination to Insulin Glargine Alone and to Lixisenatide Alone on Top of Metformin in Patients With Type 2 Diabetes Mellitus (T2DM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02058147
• Other study ID #: EFC12404
• Secondary ID: 2013-003131-30U1
• Status: Completed
• Phase: Phase 3
• First received: February 6, 2014
• Last updated: June 15, 2016
• Start date: February 2014
• Est. completion date: June 2015

Study information

• Verified date: June 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 compare the insulin glargine/lixisenatide fixed ratio combination to lixisenatide alone and to insulin glargine alone (on top of metformin treatment) 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 alone and to lixisenatide alone (on top of metformin treatment) over a 30 week treatment period in patients with type 2 diabetes

Description:

Approximately 37 weeks including up to 6 weeks of screening, 30-week treatment period, and a 3 days follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1170
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Patients with type 2 diabetes mellitus diagnosed for at least 1 year before the screening visit, treated for at least 3 months prior to visit 1 with metformin alone or metformin and a second oral anti-diabetic treatment that can be a sulfonylurea, a glinide, a sodium glucose co-transporter 2 inhibitor or a dipeptidyl peptidase 4 (DPP4) inhibitors, and who are not adequately controlled with this treatment.

• Signed written informed consent.

Exclusion criteria:

• HbA1c at screening visit:

• less than 7.5% or more than 10% for patients previously treated with metformin alone,

• less than 7.0% or more than 9 % for patients previously treated with metformin and a second oral anti-diabetic treatment.

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

• Use of oral glucose-lowering agents other than those stated in the inclusion criteria or any injectable glucose-lowering agents during the 3 months before screening.

• Previous Treatment with insulin (except for short-term treatment due to intercurrent illness including gestational diabetes, at the discretion of the trial physician).

• History of discontinuation of a previous treatment with a GLP-1 receptor agonist (GLP-1 RA) due to safety/tolerability issue 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.

• Any contraindication to metformin use, according to local labeling.

• 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).

Exclusion Criteria for randomization at the end of the screening period:

• HbA1c less than 7% or above 10%

• Fasting Plasma glucose above 250mg/dL (13.9 mmol/L)

• Metformin maximal tolerated dose less than 1500 mg/day

• 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
• Lixisenatide (AVE0010)
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
• Metformin
Pharmaceutical form: tablet Route of administration: Oral

Locations

Country	Name	City	State
Australia	Investigational Site Number 036005	Box Hill
Australia	Investigational Site Number 036001	Camperdown
Australia	Investigational Site Number 036006	Kippa Ring
Australia	Investigational Site Number 036007	Logan Central
Belgium	Investigational Site Number 056006	Brussel
Belgium	Investigational Site Number 056005	Brussels
Belgium	Investigational Site Number 056001	Leuven
Canada	Investigational Site Number 124004	Kelowna
Canada	Investigational Site Number 124001	Toronto
Canada	Investigational Site Number 124002	Vancouver
Chile	Investigational Site Number 152008	Osorno
Chile	Investigational Site Number 152015	Puerto Varas
Chile	Investigational Site Number 152001	Santiago
Chile	Investigational Site Number 152002	Santiago
Chile	Investigational Site Number 152004	Santiago
Chile	Investigational Site Number 152006	Santiago
Chile	Investigational Site Number 152009	Santiago
Chile	Investigational Site Number 152012	Santiago
Chile	Investigational Site Number 152011	Talagante
Chile	Investigational Site Number 152003	Temuco
Chile	Investigational Site Number 152014	Temuco
Czech Republic	Investigational Site Number 203004	Beroun
Czech Republic	Investigational Site Number 203008	Ceske Budejovice
Czech Republic	Investigational Site Number 203014	Horovice
Czech Republic	Investigational Site Number 203012	Koprivnice
Czech Republic	Investigational Site Number 203001	Pardubice
Czech Republic	Investigational Site Number 203005	Plzen
Czech Republic	Investigational Site Number 203003	Praha 10
Czech Republic	Investigational Site Number 203009	Praha 2
Czech Republic	Investigational Site Number 203007	Praha 5
Czech Republic	Investigational Site Number 203013	Praha 9 - Klanovice
Czech Republic	Investigational Site Number 203006	Trutnov
Czech Republic	Investigational Site Number 203016	Ujezd U Brna
Czech Republic	Investigational Site Number 203015	Vsetin
Denmark	Investigational Site Number 208003	Aarhus C
Denmark	Investigational Site Number 208009	Horsens
Denmark	Investigational Site Number 208001	København Nv
Denmark	Investigational Site Number 208005	København S
Denmark	Investigational Site Number 208002	Kolding
Denmark	Investigational Site Number 208004	Viborg
Estonia	Investigational Site Number 233004	Paide
Estonia	Investigational Site Number 233002	Pärnu
Estonia	Investigational Site Number 233003	Tallinn
Estonia	Investigational Site Number 233001	Viljandimaa
France	Investigational Site Number 250006	Corbeil Essonnes
France	Investigational Site Number 250002	La Rochelle Cedex
France	Investigational Site Number 250003	Pierre Benite
France	Investigational Site Number 250001	Venissieux
Germany	Investigational Site Number 276003	Berlin
Germany	Investigational Site Number 276005	Berlin
Germany	Investigational Site Number 276004	Dortmund
Germany	Investigational Site Number 276001	Dresden
Germany	Investigational Site Number 276007	Dresden
Germany	Investigational Site Number 276006	Hamburg
Germany	Investigational Site Number 276002	Neumünster
Hungary	Investigational Site Number 348003	Balatonfüred
Hungary	Investigational Site Number 348002	Budapest
Hungary	Investigational Site Number 348006	Budapest
Hungary	Investigational Site Number 348007	Budapest
Hungary	Investigational Site Number 348011	Komárom
Hungary	Investigational Site Number 348008	Nagykanizsa
Hungary	Investigational Site Number 348012	Sátoraljaújhely
Hungary	Investigational Site Number 348004	Szeged
Hungary	Investigational Site Number 348010	Szekesfehervar
Hungary	Investigational Site Number 348001	Zalaegerszeg
Italy	Investigational Site Number 380002	Bologna
Italy	Investigational Site Number 380006	Catanzaro
Italy	Investigational Site Number 380001	Milano
Italy	Investigational Site Number 380003	Napoli
Italy	Investigational Site Number 380005	Roma
Latvia	Investigational Site Number 428002	Riga
Latvia	Investigational Site Number 428003	Riga
Latvia	Investigational Site Number 428004	Riga
Latvia	Investigational Site Number 428001	Sigulda
Lithuania	Investigational Site Number 440003	Jonava
Lithuania	Investigational Site Number 440002	Kaunas
Lithuania	Investigational Site Number 440007	Kaunas
Lithuania	Investigational Site Number 440004	Kedainiai
Lithuania	Investigational Site Number 440006	Panevezys
Lithuania	Investigational Site Number 440005	Utena
Lithuania	Investigational Site Number 440001	Vilnius
Mexico	Investigational Site Number 484005	Aguascalientes
Mexico	Investigational Site Number 484001	Cuernavaca
Mexico	Investigational Site Number 484002	Guadalajara
Mexico	Investigational Site Number 484004	Guadalajara
Mexico	Investigational Site Number 484009	Guadalajara
Mexico	Investigational Site Number 484006	Monterrey
Mexico	Investigational Site Number 484007	Monterrey
Mexico	Investigational Site Number 484010	Zapopan
Poland	Investigational Site Number 616002	Bialystok
Poland	Investigational Site Number 616005	Krakow
Poland	Investigational Site Number 616006	Krakow
Poland	Investigational Site Number 616007	Lodz
Poland	Investigational Site Number 616004	Szczecin
Poland	Investigational Site Number 616001	Warszawa
Poland	Investigational Site Number 616003	Warszawa
Poland	Investigational Site Number 616008	Zory
Romania	Investigational Site Number 642008	Bucharest
Romania	Investigational Site Number 642007	Bucuresti
Romania	Investigational Site Number 642009	Cluj Napoca
Romania	Investigational Site Number 642006	Hunedoara
Romania	Investigational Site Number 642005	Iasi
Romania	Investigational Site Number 642002	Oradea
Romania	Investigational Site Number 642001	Targu Mures
Romania	Investigational Site Number 642003	Timisoara
Romania	Investigational Site Number 642004	Timisoara
Russian Federation	Investigational Site Number 643006	Moscow
Russian Federation	Investigational Site Number 643008	Penza
Russian Federation	Investigational Site Number 643012	Petrozavodsk
Russian Federation	Investigational Site Number 643001	Saint-Petersburg
Russian Federation	Investigational Site Number 643014	Samara
Russian Federation	Investigational Site Number 643009	Saratov
Russian Federation	Investigational Site Number 643011	Saratov
Russian Federation	Investigational Site Number 643002	St-Petersburg
Russian Federation	Investigational Site Number 643005	St-Petersburg
Russian Federation	Investigational Site Number 643007	St-Petersburg
Russian Federation	Investigational Site Number 643003	St. Petersburg
Russian Federation	Investigational Site Number 643016	Tomsk
Russian Federation	Investigational Site Number 643004	Voronezh
South Africa	Investigational Site Number 710002	Cap Town
South Africa	Investigational Site Number 710003	Cape Town
South Africa	Investigational Site Number 710005	Meyerspark
South Africa	Investigational Site Number 710007	Port Elizabeth
South Africa	Investigational Site Number 710004	Pretoria
South Africa	Investigational Site Number 710001	Somerset West
South Africa	Investigational Site Number 710006	Soweto
Spain	Investigational Site Number 724012	Barcelona
Spain	Investigational Site Number 724009	Granada
Spain	Investigational Site Number 724004	Hostalets De Balenyà
Spain	Investigational Site Number 724011	La Coruña
Spain	Investigational Site Number 724007	Lugo
Spain	Investigational Site Number 724005	Madrid
Spain	Investigational Site Number 724008	Madrid
Spain	Investigational Site Number 724013	Palma De Mallorca
Spain	Investigational Site Number 724001	Quart De Poblet
Spain	Investigational Site Number 724006	Sant Joan Despí
Spain	Investigational Site Number 724003	Sevilla
Sweden	Investigational Site Number 752001	Ljungby
Sweden	Investigational Site Number 752003	Malmö
Sweden	Investigational Site Number 752004	Rättvik
Sweden	Investigational Site Number 752005	Stockholm
Sweden	Investigational Site Number 752002	Vällingby
Ukraine	Investigational Site Number 804002	Chernivtsi
Ukraine	Investigational Site Number 804009	Ivano-Frankovsk
Ukraine	Investigational Site Number 804006	Kyiv
Ukraine	Investigational Site Number 804007	Kyiv
Ukraine	Investigational Site Number 804010	Kyiv
Ukraine	Investigational Site Number 804012	Lviv
Ukraine	Investigational Site Number 804008	Vinnytsya
Ukraine	Investigational Site Number 804011	Vinnytsya
United Kingdom	Investigational Site Number 826001	Coventry
United Kingdom	Investigational Site Number 826002	Dundee
United Kingdom	Investigational Site Number 826006	Guildford
United Kingdom	Investigational Site Number 826007	Leicester
United Kingdom	Investigational Site Number 826003	Norwich
United States	Investigational Site Number 840011	Albuquerque	New Mexico
United States	Investigational Site Number 840100	Anaheim	California
United States	Investigational Site Number 840058	Anderson	South Carolina
United States	Investigational Site Number 840075	Arlington Heights	Illinois
United States	Investigational Site Number 840039	Asheville	North Carolina
United States	Investigational Site Number 840089	Atlanta	Georgia
United States	Investigational Site Number 840097	Auburn	Maine
United States	Investigational Site Number 840059	Aurora	Colorado
United States	Investigational Site Number 840051	Austin	Texas
United States	Investigational Site Number 840008	Avon	Indiana
United States	Investigational Site Number 840015	Avon	Indiana
United States	Investigational Site Number 840076	Avon	Indiana
United States	Investigational Site Number 840065	Bell Gardens	California
United States	Investigational Site Number 840028	Bloomfield Hills	Michigan
United States	Investigational Site Number 840104	Bradenton	Florida
United States	Investigational Site Number 840112	Bristol	Tennessee
United States	Investigational Site Number 840057	Butte	Montana
United States	Investigational Site Number 840127	Charleston	South Carolina
United States	Investigational Site Number 840040	Chesapeake	Virginia
United States	Investigational Site Number 840024	Chesterfield	Missouri
United States	Investigational Site Number 840071	Chesterfield	Michigan
United States	Investigational Site Number 840026	Chicago	Illinois
United States	Investigational Site Number 840080	Chicago	Illinois
United States	Investigational Site Number 840116	Chicago	Illinois
United States	Investigational Site Number 840090	Chino	California
United States	Investigational Site Number 840002	Chula Vista	California
United States	Investigational Site Number 840004	Columbus	Ohio
United States	Investigational Site Number 840013	Concord	California
United States	Investigational Site Number 840066	Corpus Christi	Texas
United States	Investigational Site Number 840003	Dallas	Texas
United States	Investigational Site Number 840020	Dallas	Texas
United States	Investigational Site Number 840064	Dallas	Texas
United States	Investigational Site Number 840111	Dallas	Texas
United States	Investigational Site Number 840001	Dearborn	Michigan
United States	Investigational Site Number 840038	Denver	Colorado
United States	Investigational Site Number 840037	Draper	Utah
United States	Investigational Site Number 840088	Edinburg	Texas
United States	Investigational Site Number 840103	Eugene	Oregon
United States	Investigational Site Number 840031	Evansville	Indiana
United States	Investigational Site Number 840060	Evansville	Indiana
United States	Investigational Site Number 840082	Evansville	Indiana
United States	Investigational Site Number 840077	Federal Way	Washington
United States	Investigational Site Number 840118	Fort Worth	Texas
United States	Investigational Site Number 840053	Fresno	California
United States	Investigational Site Number 840049	Greer	South Carolina
United States	Investigational Site Number 840109	Henderson	Nevada
United States	Investigational Site Number 840021	Hickory	North Carolina
United States	Investigational Site Number 840055	Houston	Texas
United States	Investigational Site Number 840087	Houston	Texas
United States	Investigational Site Number 840079	Hurst	Texas
United States	Investigational Site Number 840108	Idaho Falls	Idaho
United States	Investigational Site Number 840048	Indianapolis	Indiana
United States	Investigational Site Number 840085	Indianapolis	Indiana
United States	Investigational Site Number 840091	Kalamazoo	Michigan
United States	Investigational Site Number 840094	Knoxville	Tennessee
United States	Investigational Site Number 840017	La Jolla	California
United States	Investigational Site Number 840070	Lancaster	California
United States	Investigational Site Number 840052	Las Vegas	Nevada
United States	Investigational Site Number 840054	Lawrenceville	Georgia
United States	Investigational Site Number 840022	Lexington	Kentucky
United States	Investigational Site Number 840084	Little Rock	Arkansas
United States	Investigational Site Number 840121	Long Beach	California
United States	Investigational Site Number 840044	Los Angeles	California
United States	Investigational Site Number 840126	Los Angeles	California
United States	Investigational Site Number 840007	Louisville	Kentucky
United States	Investigational Site Number 840016	Maumee	Ohio
United States	Investigational Site Number 840098	Miami	Florida
United States	Investigational Site Number 840033	Milwaukee	Wisconsin
United States	Investigational Site Number 840009	Minneapolis	Minnesota
United States	Investigational Site Number 840101	Mission Hills	California
United States	Investigational Site Number 840086	Mission Viejo	California
United States	Investigational Site Number 840120	Mission Viejo	California
United States	Investigational Site Number 840046	Morehead City	North Carolina
United States	Investigational Site Number 840072	Morganton	North Carolina
United States	Investigational Site Number 840123	Morganville	New Jersey
United States	Investigational Site Number 840073	N Richland Hill	Texas
United States	Investigational Site Number 840069	Nashua	New Hampshire
United States	Investigational Site Number 840030	New Hyde Park	New York
United States	Investigational Site Number 840081	New Orleans	Louisiana
United States	Investigational Site Number 840014	New Port Richey	Florida
United States	Investigational Site Number 840045	Norfolk	Virginia
United States	Investigational Site Number 840092	Norfolk	Virginia
United States	Investigational Site Number 840005	Northridge	California
United States	Investigational Site Number 840047	Ocoee	Florida
United States	Investigational Site Number 840093	Ogden	Utah
United States	Investigational Site Number 840042	Omaha	Nebraska
United States	Investigational Site Number 840056	Palm Harbor	Florida
United States	Investigational Site Number 840034	Palm Springs	California
United States	Investigational Site Number 840027	Phoenix	Arizona
United States	Investigational Site Number 840122	Phoenix	Arizona
United States	Investigational Site Number 840036	Pittsburgh	Pennsylvania
United States	Investigational Site Number 840074	Port Hueneme	California
United States	Investigational Site Number 840113	Portland	Oregon
United States	Investigational Site Number 840114	Rapid City	South Dakota
United States	Investigational Site Number 840102	Renton	Washington
United States	Investigational Site Number 840125	Richmond	Virginia
United States	Investigational Site Number 840063	Rockville	Maryland
United States	Investigational Site Number 840115	Salem	Virginia
United States	Investigational Site Number 840110	Salisbury	North Carolina
United States	Investigational Site Number 840041	Salt Lake City	Utah
United States	Investigational Site Number 840061	Salt Lake City	Utah
United States	Investigational Site Number 840019	San Antonio	Texas
United States	Investigational Site Number 840068	San Ramon	California
United States	Investigational Site Number 840067	Santa Ana	California
United States	Investigational Site Number 840050	Springfield	Illinois
United States	Investigational Site Number 840096	Syracuse	New York
United States	Investigational Site Number 840029	Tarzana	California
United States	Investigational Site Number 840006	Temecula	California
United States	Investigational Site Number 840023	Tempe	Arizona
United States	Investigational Site Number 840062	Tempe	Arizona
United States	Investigational Site Number 840043	Tipton	Pennsylvania
United States	Investigational Site Number 840012	Valparaiso	Indiana
United States	Investigational Site Number 840025	Waterloo	Iowa
United States	Investigational Site Number 840010	Weber City	Virginia
United States	Investigational Site Number 840078	West Hills	California
United States	Investigational Site Number 840095	Wilmington	North Carolina
United States	Investigational Site Number 840099	Winston-Salem	North Carolina
United States	Investigational Site Number 840119	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Chile,  Czech Republic,  Denmark,  Estonia,  France,  Germany,  Hungary,  Italy,  Latvia,  Lithuania,  Mexico,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Sweden,  Ukraine,  United Kingdom, 

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		week 30	No
Secondary	Change in body weight from baseline		week 30	No
Secondary	Change in 7-point Self Measured Plasma Glucose profiles from baseline		week 30	No
Secondary	Daily dose of insulin glargine		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		week 30	Yes
Secondary	Severe symptomatic hypoglycemia		week 30	Yes