Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure

NCT ID: NCT01117350

Last Updated: 2014-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 978 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2013-03-31

Brief Summary

Primary objective:

To demonstrate the superiority of insulin glargine over liraglutide in terms of percentage of patients reaching a Glycosylated Haemoglobin (HbA1c) < 7% at the end of the comparative period (24 weeks) in Type 2 diabetic patients failing lifestyle management and oral agents

Secondary objectives of the comparative period (24 weeks):

>To assess the effect of insulin glargine in comparison with liraglutide on:

• HbA1c level
• Percentage of patients whose HbA1c has decreased but remains >= 7% at the end of the comparative period
• Percentage of patients whose HbA1c has increased at the end of the comparative period
• Fasting Plasma Glucose (FPG)
• 7-point Plasma Glucose (PG) profiles
• Hypoglycemia occurrence
• Body weight
• Adverse events

Objectives of the extension period (24 weeks):

>To assess the effect of insulin glargine in patients not adequately controlled with liraglutide on:

• HbA1c level
• FPG
• 7-point PG profiles
• Hypoglycemia occurrence
• Body weight
• Adverse events

Detailed Description

Maximum estimated study duration per patient: either 27 weeks (patients randomized to insulin glargine arm) or 51 weeks (patients randomized to liraglutide arm) broken down as follow:

• A 2-week of screening period,
• A 24-week comparative period,
• A 24-week extension period (only for patients treated with liraglutide, not adequately controlled at the end of the comparative period),
• A 1-week follow-up period

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Insulin Glargine

Insulin glargine administered once a day, in the morning or in the evening, at the most convenient time. The time of injection, once chosen was to remain unchanged during the whole duration of the study.

The starting dose was 0.2 Unit per kilogram of body weight or 10 Units. Patients were empowered to adjust their insulin doses, under strict investigator's supervision. Insulin titration (by 2 or 4 Units) was done every 3 days according to the median value of Fasting Plasma Glucose (FPG) of the last 3 days. The goal was to achieve 70 < FPG ≤ 100 mg/dL (3.9 < FPG ≤ 5.5 mmol/L). Minor deviations from the titration scheme could be allowed, based on Investigator's judgment and patient's situation.

Group Type: EXPERIMENTAL

Insulin glargine

Intervention Type: DRUG

100 Units/mL solution for injection in a pre-filled SoloStar pen

Metformin

Intervention Type: DRUG

Metformin was a background treatment, mandatory for each patient randomized in the study (at the minimum dose of 1g/day). It was not supplied by the sponsor.

Liraglutide

Liraglutide administered once a day, in the morning or in the evening, at the most convenient time. The time of injection , once chosen was to remain unchanged during the whole duration of the study.

The dose was 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24. The dose might be decreased to 1.2 mg for safety reasons (e.g. gastro-intestinal tolerability), based on Investigator's judgment.

Group Type: ACTIVE_COMPARATOR

Liraglutide

Intervention Type: DRUG

6 mg/mL solution for injection in a 3-mL pre-filled pen (18mg)

Metformin

Intervention Type: DRUG

Metformin was a background treatment, mandatory for each patient randomized in the study (at the minimum dose of 1g/day). It was not supplied by the sponsor.

Interventions

Insulin glargine

100 Units/mL solution for injection in a pre-filled SoloStar pen

Intervention Type: DRUG

Liraglutide

6 mg/mL solution for injection in a 3-mL pre-filled pen (18mg)

Intervention Type: DRUG

Metformin

Metformin was a background treatment, mandatory for each patient randomized in the study (at the minimum dose of 1g/day). It was not supplied by the sponsor.

Intervention Type: DRUG

Other Intervention Names

Lantus®; Victoza®

Eligibility Criteria

Inclusion Criteria

• Patients With Type 2 Diabetes diagnosed for at least 1 year,
• Treated with lifestyle interventions and metformin at the maximum tolerated dosage (with a minimum daily dosage of 1g), either alone or in combination with an oral insulin secretagogue (sulfonylurea, glinide or DiPeptidyl Peptidase IV inhibitor), for more than 3 months,
• 7.5% < HbA1c <= 12%,
• Body Mass Index (BMI) between 25 and 40 kg/m2 inclusively,
• Ability and willingness to perform PG (Plasma Glucose) self monitoring using the sponsor-provided glucose meter and to complete the patient diary,
• Willingness and ability to comply with the study protocol,
• Signed informed consent obtained prior to any study procedure.

• Patients treated with liraglutide (at the maximal tolerated dosage), having a mean FPG ≥ 250 mg/dL at visit 10 (Week 12) or visit 11 (Week 18), or a HbA1c≥ 7% at visit 12 (Week 24)

Exclusion Criteria

• Previous treatment with Glucagon Like Peptide-1 analogues or insulin in the past year (except in case of temporary treatment for gestational diabetes, surgery, hospitalization...),
• Treatment with thiazolidinediones or α-Glucosidases inhibitors within 3 months prior to study entry,
• Diabetes other than Type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake),
• Pregnant women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method),
• Lactating women,
• Hospitalized patients (except hospitalization for routine diabetes check-up),
• Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by a retina examination within 2 years prior to study entry,
• Impaired renal function (creatinine clearance < 60 mL/mn),
• Impaired hepatic function (Alanine Aminotransferase, Aspartate Aminotransferase 2.5 times the upper limit of normal range),
• Personal or family history of medullary thyroid carcinoma,
• Multiple endocrine neoplasia syndrome type 2,
• Severe gastro-intestinal disease (including inflammatory bowel disease or diabetic gastroparesis),
• Congestive heart failure,
• History of acute pancreatitis,
• Treatment with corticosteroids with potential systemic action for more than 10 days within 3 months prior to study entry,
• Alcohol or drug abuse in the past 5 years,
• History of sensitivity to the study drugs or to drugs with a similar chemical structure.
• Night shift worker,
• Presence of any condition (medical, psychological, social or geographical), current or anticipated that would compromise the patients safety or limit the patient successful participation in the study,
• Participation in a clinical trial (drug or device) within 3 months prior to study entry,
• Refusal or inability to give informed consent to participate in the study,
• Patient is the Investigator or any sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

• Treatment with oral antidiabetic drugs other than metformin and patient's usual sulfonylurea if any, or with insulin during the comparative period (except in case of an emergency, for a period of time less than 7 days),
• Treatment with corticosteroids with potential systemic action within the last 3 months of the comparative period.
• History of sensitivity to insulin glargine.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840023

Birmingham, Alabama, United States

Investigational Site Number 840002

Goodyear, Arizona, United States

Investigational Site Number 840047

Phoenix, Arizona, United States

Investigational Site Number 840017

La Jolla, California, United States

Investigational Site Number 840036

La Mesa, California, United States

Investigational Site Number 840037

Loma Linda, California, United States

Investigational Site Number 840045

Long Beach, California, United States

Investigational Site Number 840048

Mission Hills, California, United States

Investigational Site Number 840033

Mission Viejo, California, United States

Investigational Site Number 840019

Palm Springs, California, United States

Investigational Site Number 840039

San Diego, California, United States

Investigational Site Number 840042

San Diego, California, United States

Investigational Site Number 840043

Tustin, California, United States

Investigational Site Number 840028

Denver, Colorado, United States

Investigational Site Number 840034

Grand Junction, Colorado, United States

Investigational Site Number 840026

Longmont, Colorado, United States

Investigational Site Number 840022

Lawrenceville, Georgia, United States

Investigational Site Number 840029

Roswell, Georgia, United States

Investigational Site Number 840009

Arlington Heights, Illinois, United States

Investigational Site Number 840051

Springfield, Illinois, United States

Investigational Site Number 840050

Indianapolis, Indiana, United States

Investigational Site Number 840031

Kansas City, Kansas, United States

Investigational Site Number 840004

Paducah, Kentucky, United States

Investigational Site Number 840010

Rockville, Maryland, United States

Investigational Site Number 840038

Eagan, Minnesota, United States

Investigational Site Number 840030

Minneapolis, Minnesota, United States

Investigational Site Number 840012

St Louis, Missouri, United States

Investigational Site Number 840044

St Louis, Missouri, United States

Investigational Site Number 840015

Atco, New Jersey, United States

Investigational Site Number 840008

Blackwood, New Jersey, United States

Investigational Site Number 840027

Mineola, New York, United States

Investigational Site Number 840011

Staten Island, New York, United States

Investigational Site Number 840005

Hickory, North Carolina, United States

Investigational Site Number 840052

Winston-Salem, North Carolina, United States

Investigational Site Number 840049

Fargo, North Dakota, United States

Investigational Site Number 840006

Bryan, Ohio, United States

Investigational Site Number 840035

Cincinnati, Ohio, United States

Investigational Site Number 840016

Carnegie, Pennsylvania, United States

Investigational Site Number 840020

Uniontown, Pennsylvania, United States

Investigational Site Number 840024

Rapid City, South Dakota, United States

Investigational Site Number 840001

Dallas, Texas, United States

Investigational Site Number 840007

Dallas, Texas, United States

Investigational Site Number 840013

Houston, Texas, United States

Investigational Site Number 840014

Renton, Washington, United States

Investigational Site Number 840046

Spokane, Washington, United States

Investigational Site Number 040-006

Salzburg, , Austria

Investigational Site Number 040-007

Salzburg, , Austria

Investigational Site Number 040-003

Stockerau, , Austria

Investigational Site Number 040-005

Vienna, , Austria

Investigational Site Number 040-002

Vienna, , Austria

Investigational Site Number 040-001

Vienna, , Austria

Investigational Site Number 040-004

Vienna, , Austria

Investigational Site Number 076-004

Belém, , Brazil

Investigational Site Number 076-007

Fortaleza, , Brazil

Investigational Site Number 076-001

Fortaleza, , Brazil

Investigational Site Number 076-006

Fortaleza, , Brazil

Investigational Site Number 076-005

Marília, , Brazil

Investigational Site Number 076-002

São Paulo, , Brazil

Investigational Site Number 124-003

Mississauga, , Canada

Investigational Site Number 124-001

Montreal, , Canada

Investigational Site Number 124-006

Montreal, , Canada

Investigational Site Number 124-004

Toronto, , Canada

Investigational Site Number 124-008

Vancouver, , Canada

Investigational Site Number 124-007

Victoria, , Canada

Investigational Site Number 203001

Hradec Králové, , Czechia

Investigational Site Number 203003

Krnov, , Czechia

Investigational Site Number 203005

Kroměříž, , Czechia

Investigational Site Number 203002

Olomouc, , Czechia

Investigational Site Number 203006

Prague, , Czechia

Investigational Site Number 246003

Harjavalta, , Finland

Investigational Site Number 246001

Kuopio, , Finland

Investigational Site Number 246002

Oulu, , Finland

Investigational Site Number 246004

Turku, , Finland

Investigational Site Number 250-007

Annecy, , France

Investigational Site Number 250-017

Bois-Guillaume, , France

Investigational Site Number 250-003

Boulogne-Billancourt, , France

Investigational Site Number 250-011

Brest, , France

Investigational Site Number 250-008

Cahors, , France

Investigational Site Number 250-012

Corbeil-Essonnes, , France

Investigational Site Number 250-009

La Rochelle, , France

Investigational Site Number 250-004

Le Creusot, , France

Investigational Site Number 250-006

Mantes-la-Jolie, , France

Investigational Site Number 250-021

Nanterre, , France

Investigational Site Number 250022

Strasbourg, , France

Investigational Site Number 250-020

Strasbourg, , France

Investigational Site Number 250-002

Toulouse, , France

Investigational Site Number 250-016

Vénissieux, , France

Investigational Site Number 300003

Athens, , Greece

Investigational Site Number 300004

Athens, , Greece

Investigational Site Number 300001

Haidari, Athens, , Greece

Investigational Site Number 372001

Dublin, , Ireland

Investigational Site Number 376004

Hadera, , Israel

Investigational Site Number 376002

Petah Tikva, , Israel

Investigational Site Number 376003

Tel Aviv, , Israel

Investigational Site Number 484004

Guadalajara, , Mexico

Investigational Site Number 484001

México, , Mexico

Investigational Site Number 484002

México, , Mexico

Investigational Site Number 484003

Zapopan, , Mexico

Investigational Site Number 528004

's-Hertogenbosch, , Netherlands

Investigational Site Number 528001

Beek, , Netherlands

Investigational Site Number 528006

Enschede, , Netherlands

Investigational Site Number 528002

Hoogeveen, , Netherlands

Investigational Site Number 528007

Nijverdal, , Netherlands

Investigational Site Number 528003

Rotterdam, , Netherlands

Investigational Site Number 528005

Woerden, , Netherlands

Investigational Site Number 643-009

Kazan', , Russia

Investigational Site Number 643008

Kirov, , Russia

Investigational Site Number 643001

Moscow, , Russia

Investigational Site Number 643004

Saint Petersburg, , Russia

Investigational Site Number 643006

Samara, , Russia

Investigational Site Number 643007

Samara, , Russia

Investigational Site Number 643005

Saratov, , Russia

Investigational Site Number 643003

St-Ptetersburg, , Russia

Investigational Site Number 703002

Bratislava, , Slovakia

Investigational Site Number 703004

Košice, , Slovakia

Investigational Site Number 703001

Nitra, , Slovakia

Investigational Site Number 703005

Nové Mesto nad Váhom, , Slovakia

Investigational Site Number 703003

Žilina, , Slovakia

Investigational Site Number 724007

Bilbao, , Spain

Investigational Site Number 724006

Cadiz, , Spain

Investigational Site Number 724001

Las Palmas de Gran Canaria, , Spain

Investigational Site Number 724005

Lleida, , Spain

Investigational Site Number 724008

Madrid, , Spain

Investigational Site Number 724003

Málaga, , Spain

Investigational Site Number 724009

Sabadell, , Spain

Investigational Site Number 721002

Valencia, , Spain

Investigational Site Number 724004

Valencia, , Spain

Investigational Site Number 724010

Vigo, , Spain

Investigational Site Number 752-03

Ängelholm, , Sweden

Investigational Site Number 752-002

Gothenburg, , Sweden

Investigational Site Number 752-005

Karlskoga, , Sweden

Investigational Site Number 752-006

Motala, , Sweden

Investigational Site Number 752-007

Örebro, , Sweden

Investigational Site Number 752-001

Stockholm, , Sweden

Investigational Site Number 792-001

Antalya, , Turkey (Türkiye)

Investigational Site Number 792-002

Istanbul, , Turkey (Türkiye)

Countries

United States; Austria; Brazil; Canada; Czechia; Finland; France; Greece; Ireland; Israel; Mexico; Netherlands; Russia; Slovakia; Spain; Sweden; Turkey (Türkiye)

Other Identifiers

2010-018437-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1116-9684

Identifier Type: OTHER

Identifier Source: secondary_id

LANTU_C_03680

Identifier Type: -

Identifier Source: org_study_id