Efficacy and Safety of Lixisenatide Versus Insulin Glulisine on Top of Insulin Glargine With or Without Metformin in Type 2 Diabetic Patients

Type 2 Diabetes Clinical Trial

— GetGoal Duo-2  

Official title:

A Randomized, Open-label, Active-controlled, 3-arm Parallel-group, 26-week Study Comparing the Efficacy and Safety of Lixisenatide to That of Insulin Glulisine Once Daily and Insulin Glulisine Three Times Daily in Patients With Type 2 Diabetes Insufficiently Controlled With Insulin Glargine With or Without Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01768559
• Other study ID #: EFC12626
• Secondary ID: 2012-004096-38U1
• Status: Completed
• Phase: Phase 3
• First received: January 11, 2013
• Last updated: December 2, 2015
• Start date: January 2013
• Est. completion date: December 2014

Study information

• Verified date: December 2015
• 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 lixisenatide versus insulin glulisine in terms of HbA1c reduction and body weight change at week 26 in type 2 diabetic patients not adequately controlled on insulin glargine ± metformin.

Secondary Objectives:

• To compare the treatments/regimens on:

• The percentage of patients reaching the target of HbA1c <7% or ≤6.5%

• Body weight

• Self-Monitored Glucose profiles

• Fasting Plasma Glucose (FPG)

• Post-prandial plasma glucose /glucose excursions during a standardized meal test (subset of patients)

• Daily doses of insulins

• Safety and tolerability

Description:

Approximately 41 weeks including a 26 week treatment period

Recruitment information / eligibility

• Status: Completed
• Enrollment: 894
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Patients with type 2 diabetes mellitus diagnosed at least 1 year before screening visit (V1) .

• Patients treated with basal insulin for at least 6 months.

• Patients treated for at least 3 months prior to visit 1 with a stable basal insulin regimen (ie type of insulin and time/frequency of the injection). The insulin dose should be stable (± 20 %) and =20 U/day for at least 2 months prior to visit 1.

• Patients treated with basal insulin alone or in combination with 1 to 3 oral anti-diabetic drugs (OADs) that can be: metformin (=1.5g/day or maximal tolerated dose), a sulfonylurea (SU), a dipeptidyl-peptidase-4 (DPP-4) inhibitor, a glinide. The dose of OADs should be stable for at least 3 months prior to visit 1.

Exclusion criteria:

• At screening: age < legal age of majority

• At screening, HbA1c: < 7.5% and > 10.0% for patients treated with basal insulin alone or in combination with metformin only; < 7.0% and > 10.0% for patients treated with basal insulin and a combination of oral anti-diabetic drugs which includes a SU and/or a DPP-4 inhibitor and/or a glinide.

• Women of childbearing potential with no effective contraceptive method, pregnancy or lactation

• Type 1 diabetes mellitus

• Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria within 3 months prior to screening.

• Previous treatment with short or rapid acting insulin other than in relation to hospitalization or an acute illness.

• Any previous treatment with lixisenatide, or any discontinuation from another GLP-1 receptor agonist due to safety/tolerability issue or lack of efficacy.

• At screening, Body Mass Index (BMI) =20 or >40 kg/m².

• Weight change of more than 5 kg during the 3 months prior to the screening visit; use of weight loss drugs within 3 months prior to screening.

• Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures.

• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.

• At screening resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 95 mmHg

• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes)

• Contraindication related to metformin (for patient receiving this treatment), insulin glargine, insulin glulisine or lixisenatide.

• Patients with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease.

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

• At screening ALT or AST>3ULN

• At screening calcitonin =20 pg/ml (5.9 pmol/L)

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

• HbA1c <7.0% or >9.0%.

• 7-day mean fasting SMPG >140 mg/dl (7.8 mmol/L).

• Amylase and/or lipase > 3 times 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:
• lixisenatide (AVE0010)
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
• insulin glulisine (HMR1964)
Pharmaceutical form:solution for injection (disposable self injector) Route of administration: subcutaneous injection
• Insulin Glargine
Doses to be adjusted to maintain a fasting SMPG between 4.4 to 5.6 mmol/L (80 to 100 mg/dL)
• Metformin
If previously taken Metformin to be continued at stable dose ( =1.5 g/day) throughout the study

Locations

Country	Name	City	State
Canada	Investigational Site Number 124008	Brampton
Canada	Investigational Site Number 124015	Burlington
Canada	Investigational Site Number 124018	Chatham
Canada	Investigational Site Number 124004	Coquitlam
Canada	Investigational Site Number 124016	Etobicoke
Canada	Investigational Site Number 124014	Hamilton
Canada	Investigational Site Number 124011	Montreal
Canada	Investigational Site Number 124020	Montreal
Canada	Investigational Site Number 124017	Newmarket
Canada	Investigational Site Number 124021	Quebec
Canada	Investigational Site Number 124003	Red Deer
Canada	Investigational Site Number 124002	Sherbrooke
Canada	Investigational Site Number 124012	St-Romuald
Canada	Investigational Site Number 124001	Toronto
Canada	Investigational Site Number 124010	Toronto
Canada	Investigational Site Number 124005	Vancouver
Canada	Investigational Site Number 124006	Victoria
Canada	Investigational Site Number 124007	Winnipeg
Chile	Investigational Site Number 152101	Santiago
Chile	Investigational Site Number 152102	Santiago
Chile	Investigational Site Number 152103	Santiago
Chile	Investigational Site Number 152105	Santiago
Chile	Investigational Site Number 152106	Santiago
Chile	Investigational Site Number 152107	Santiago
Chile	Investigational Site Number 152108	Santiago
Chile	Investigational Site Number 152109	Santiago
Czech Republic	Investigational Site Number 203107	Beroun
Czech Republic	Investigational Site Number 203103	Jilove U Prahy
Czech Republic	Investigational Site Number 203101	Ostrava 2
Czech Republic	Investigational Site Number 203110	Police Nad Metuji
Czech Republic	Investigational Site Number 203102	Praha 4
Czech Republic	Investigational Site Number 203105	Praha 4
Czech Republic	Investigational Site Number 203108	Praha 4
Czech Republic	Investigational Site Number 203104	Trutnov
Estonia	Investigational Site Number 233102	Pärnu
Estonia	Investigational Site Number 233103	Tallinn
Estonia	Investigational Site Number 233104	Tallinn
Estonia	Investigational Site Number 233101	Viljandimaa
France	Investigational Site Number 250108	Bois Guillaume
France	Investigational Site Number 250105	Corbeil Essonnes
France	Investigational Site Number 250104	La Rochelle Cedex
France	Investigational Site Number 250106	Lyon
France	Investigational Site Number 250107	Lyon
France	Investigational Site Number 250109	Mantes La Jolie
France	Investigational Site Number 250102	Paris Cedex 15
France	Investigational Site Number 250101	Vandoeuvre Les Nancy
France	Investigational Site Number 250103	Venissieux
Germany	Investigational Site Number 276112	Bad Mergentheim
Germany	Investigational Site Number 276108	Berlin
Germany	Investigational Site Number 276102	Dortmund
Germany	Investigational Site Number 276106	Dresden
Germany	Investigational Site Number 276120	Dresden
Germany	Investigational Site Number 276117	Frankfurt A.M.
Germany	Investigational Site Number 276116	Görlitz
Germany	Investigational Site Number 276113	Heidelberg
Germany	Investigational Site Number 276118	Leipzig
Germany	Investigational Site Number 276119	Magdeburg
Germany	Investigational Site Number 276103	Neumünster
Germany	Investigational Site Number 276115	Speyer
Germany	Investigational Site Number 276109	St. Ingbert-Oberwürzbach
Hungary	Investigational Site Number 348102	Budapest
Hungary	Investigational Site Number 348107	Budapest
Hungary	Investigational Site Number 348108	Budapest
Hungary	Investigational Site Number 348101	Eger
Hungary	Investigational Site Number 348103	Pápa
Hungary	Investigational Site Number 348106	Sátoraljaújhely
Hungary	Investigational Site Number 348104	Szeged
Hungary	Investigational Site Number 348105	Zalaegerszeg
Italy	Investigational Site Number 380103	Bologna
Italy	Investigational Site Number 380102	Catania
Italy	Investigational Site Number 380101	Milano
Italy	Investigational Site Number 380105	Napoli
Italy	Investigational Site Number 380104	Torino
Latvia	Investigational Site Number 428103	Jelgava
Latvia	Investigational Site Number 428104	Ogre
Latvia	Investigational Site Number 428102	Riga
Latvia	Investigational Site Number 428105	Riga
Latvia	Investigational Site Number 428101	Sigulda
Lithuania	Investigational Site Number 440104	Jonava
Lithuania	Investigational Site Number 440101	Kaunas
Lithuania	Investigational Site Number 440102	Kaunas
Lithuania	Investigational Site Number 440103	Kaunas
Lithuania	Investigational Site Number 440105	Klaipeda
Mexico	Investigational Site Number 484108	Chihuahua
Mexico	Investigational Site Number 484101	Cuernavaca
Mexico	Investigational Site Number 484111	Durango
Mexico	Investigational Site Number 484104	Guadalajara
Mexico	Investigational Site Number 484105	Guadalajara
Mexico	Investigational Site Number 484107	Guadalajara
Mexico	Investigational Site Number 484109	Guadalajara
Mexico	Investigational Site Number 484110	Guadalajara
Mexico	Investigational Site Number 484102	México
Mexico	Investigational Site Number 484103	Mexico Df
Mexico	Investigational Site Number 484106	Monterrey
Poland	Investigational Site Number 616101	Bialystok
Poland	Investigational Site Number 616103	Bydgoszcz
Poland	Investigational Site Number 616102	Bytom
Poland	Investigational Site Number 616104	Krakow
Poland	Investigational Site Number 616106	Krakow
Poland	Investigational Site Number 616105	Pulawy
Poland	Investigational Site Number 616107	Warszawa
Romania	Investigational Site Number 642105	Bacau
Romania	Investigational Site Number 642108	Cluj Napoca
Romania	Investigational Site Number 642106	Deva
Romania	Investigational Site Number 642113	Galati
Romania	Investigational Site Number 642107	Hunedoara
Romania	Investigational Site Number 642117	Iasi
Romania	Investigational Site Number 642103	Oradea
Romania	Investigational Site Number 642104	Oradea
Romania	Investigational Site Number 642112	Pitesti
Romania	Investigational Site Number 642114	Ploiesti
Romania	Investigational Site Number 642102	Resita
Romania	Investigational Site Number 642111	Sibiu
Romania	Investigational Site Number 642109	Targu Mures
Romania	Investigational Site Number 642110	Targu Mures
Romania	Investigational Site Number 642101	Timisoara
Romania	Investigational Site Number 642115	Timisoara
Romania	Investigational Site Number 642116	Timisoara
Russian Federation	Investigational Site Number 643105	Moscow
Russian Federation	Investigational Site Number 643107	Moscow
Russian Federation	Investigational Site Number 643111	Moscow
Russian Federation	Investigational Site Number 643110	Penza
Russian Federation	Investigational Site Number 643102	Saratov
Russian Federation	Investigational Site Number 643101	St-Petersburg
Russian Federation	Investigational Site Number 643103	St-Petersburg
Russian Federation	Investigational Site Number 643104	St-Petersburg
Russian Federation	Investigational Site Number 643108	St-Petersburg
Russian Federation	Investigational Site Number 643109	St-Petersburg
Russian Federation	Investigational Site Number 643106	St. Petersburg
Spain	Investigational Site Number 724102	El Ferrol
Spain	Investigational Site Number 724105	La Coruña
Spain	Investigational Site Number 724103	Malaga
Spain	Investigational Site Number 724104	Sevilla
Ukraine	Investigational Site Number 804104	Chernivtsi
Ukraine	Investigational Site Number 804103	Donetsk
Ukraine	Investigational Site Number 804107	Donetsk
Ukraine	Investigational Site Number 804108	Mykolaiv
Ukraine	Investigational Site Number 804110	Odessa
Ukraine	Investigational Site Number 804102	Vinnytsya
Ukraine	Investigational Site Number 804105	Vinnytsya
Ukraine	Investigational Site Number 804111	Zaporizhia
United Kingdom	Investigational Site Number 826006	Ashton-Under-Lyne
United Kingdom	Investigational Site Number 826002	Birmingham
United Kingdom	Investigational Site Number 826007	Carmarthen
United Kingdom	Investigational Site Number 826005	Chester
United Kingdom	Investigational Site Number 826008	Coventry
United Kingdom	Investigational Site Number 826009	Dundee
United Kingdom	Investigational Site Number 826001	Durham
United Kingdom	Investigational Site Number 826011	Haddington
United Kingdom	Investigational Site Number 826012	Leicester
United Kingdom	Investigational Site Number 826010	Plymouth
United Kingdom	Investigational Site Number 826004	Sheffield
United Kingdom	Investigational Site Number 826003	St Helens
United States	Investigational Site Number 840004	Avon	Indiana
United States	Investigational Site Number 840055	Avon	Indiana
United States	Investigational Site Number 840016	Baltimore	Maryland
United States	Investigational Site Number 840025	Buckley	Michigan
United States	Investigational Site Number 840032	Chattanooga	Tennessee
United States	Investigational Site Number 840024	Chicago	Illinois
United States	Investigational Site Number 840034	Corpus Christi	Texas
United States	Investigational Site Number 840001	Dallas	Texas
United States	Investigational Site Number 840048	Dearborn	Michigan
United States	Investigational Site Number 840041	Denver	Colorado
United States	Investigational Site Number 840027	Des Moines	Iowa
United States	Investigational Site Number 840009	Evanston	Illinois
United States	Investigational Site Number 840028	Fargo	North Dakota
United States	Investigational Site Number 840020	Houston	Texas
United States	Investigational Site Number 840026	Kalamazoo	Michigan
United States	Investigational Site Number 840031	La Mesa	California
United States	Investigational Site Number 840049	Las Vegas	Nevada
United States	Investigational Site Number 840045	Lawrenceville	Georgia
United States	Investigational Site Number 840047	Lexington	Kentucky
United States	Investigational Site Number 840003	Little Rock	Arkansas
United States	Investigational Site Number 840022	Marrero	Louisiana
United States	Investigational Site Number 840012	Miami	Florida
United States	Investigational Site Number 840061	Miami	Florida
United States	Investigational Site Number 840010	Milwaukee	Wisconsin
United States	Investigational Site Number 840005	Mission Viejo	California
United States	Investigational Site Number 840052	Myrtle Beach	South Carolina
United States	Investigational Site Number 840036	Nampa	Idaho
United States	Investigational Site Number 840033	Nashville	Tennessee
United States	Investigational Site Number 840029	New Hyde Park	New York
United States	Investigational Site Number 840018	Norfolk	Virginia
United States	Investigational Site Number 840057	Northridge	California
United States	Investigational Site Number 840007	Oklahoma City	Oklahoma
United States	Investigational Site Number 840056	Paducah	Kentucky
United States	Investigational Site Number 840021	Pittsburgh	Pennsylvania
United States	Investigational Site Number 840017	Rockville	Maryland
United States	Investigational Site Number 840015	Salem	Virginia
United States	Investigational Site Number 840011	Salisbury	North Carolina
United States	Investigational Site Number 840035	Santa Ana	California
United States	Investigational Site Number 840060	Smithtown	New York
United States	Investigational Site Number 840030	Staten Island	New York
United States	Investigational Site Number 840043	Sun City	Arizona
United States	Investigational Site Number 840002	Temecula	California
United States	Investigational Site Number 840042	Tempe	Arizona
United States	Investigational Site Number 840037	Walnut Creek	California
United States	Investigational Site Number 840023	West Hills	California
United States	Investigational Site Number 840006	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Czech Republic,  Estonia,  France,  Germany,  Hungary,  Italy,  Latvia,  Lithuania,  Mexico,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in HbA1c		week 26	No
Primary	Change from baseline in body weight		week 26	No
Secondary	Percentage of patients reaching HbA1c <7%		week 26	No
Secondary	Percentage of patients reaching HbA1c =6.5%		week 26	No
Secondary	Change in body weight from baseline		week 26	No
Secondary	Percentage of patients with no weight gain		week 26	No
Secondary	Change in 7-point SMPG profiles from baseline		week 26	No
Secondary	Change from baseline in FPG		week 26	No
Secondary	Change from baseline in post-prandial glucose /glucose excursions during a standardized meal test (subset of patients)		week 26	No
Secondary	Change from baseline in insulin glargine dose		week 26	No
Secondary	Daily dose of insulin glulisine		week 26	No
Secondary	Total daily dose of insulin		week 26	No
Secondary	Documented (PG <60 mg/dl) symptomatic hypoglycemia (percentage of subjects with at least one episode, number of events per patient-year)		26 weeks	Yes
Secondary	Severe hypoglycemia		26 weeks	Yes